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Reactive oxygen species production in mitochondria of human gingival fibroblast induced by blue light irradiation
Abstract
In recent years, it has become well known that the production of reactive oxygen species (ROS) induced by blue-light irradiation causes adverse effects of photo-aging, such as age-related macular degeneration of the retina. Thus, orange-tinted glasses are used to protect the retina during dental treatment involving blue-light irradiation (e.g., dental resin restorations or tooth bleaching treatments). However, there are few studies examining the effects of blue-light irradiation on oral tissue. For the first time, we report that blue-light irradiation by quartz tungsten halogen lamp (QTH) or light-emitting diode (LED) decreased cell proliferation activity of human gingival fibroblasts (HGFs) in a time-dependent manner (<5min). Additionally, in a morphological study, the cytotoxic effect was observed in the cell organelles, especially the mitochondria. Furthermore, ROS generation induced by the blue-light irradiation was detected in mitochondria of HGFs using fluorimetry. In all analyses, the cytotoxicity was significantly higher after LED irradiation compared with cytotoxicity after QTH irradiation. These results suggest that blue light irradiation, especially by LED light sources used in dental aesthetic treatment, might have adverse effects on human gingival tissue. Hence, this necessitates the development of new dental aesthetic treatment methods and/or techniques to protect HGFs from blue light irradiation during dental therapy.
... However, blue LED light with wavelengths of 400-500 nm may be cytotoxic and cause injury to the skin, eyes, and some other human tissues. This danger is popularly known as a ''blue light hazard'' [166,167]. ...
... It has been suggested that the gingival tissue may be highly affected by blue-light irradiation [151]. Due to short-wavelength irradiation, blue LED light in dental treatments may generate ROS species, including HO• and H 2 O 2 , in gingival fibroblasts [166]. ROS production reportedly can be significant, causing damage to mitochondria and decreasing cell proliferation activity of human gingival fibroblasts (HGFs) in a time-dependent manner. ...
... In summary, the use of blue LED-light irradiation in dental aesthetic treatment is accompanied by adverse effects on human gingival tissue. This poses a huge challenge to the development of LED-light phototherapy in the dental aesthetic field, which necessitates the development of new techniques to protect HGFs from the harmful effects of blue LED light during the treatment process [166]. ...
Photobiomodulation Therapy (PBMT) is a novel modality using irradiation with light-power-intensity light. Recently, applications of PBMT have been broadened to thousands of people around the world for various medical conditions and dermatological conditions. Normally, light sources used in PBMT are non-coherent light (Light Emitting Diodes-LED) or coherent light (lasers). LED-light-source-based devices offer several advantages compared with laser devices, including ease of home use, simultaneous irradiation of a large area of tissue, availability for wearable devices, much lower price, and enhanced safety. Thus, various LED-based devices for dermatological and cosmetics applications have been designed and developed and sold on the global market. However, LED therapy still confronts many challenges that limit its applications and cause human-health concerns. Herein, we provide a critical review of the various applications of LED therapy in the fields of dermatology and beauty: skin rejuvenation, acne treatment, scarring prevention, hair restoration, fat reduction and cellulite treatment, and tooth whitening. Also, the challenges to the development of LED therapy and its action mechanisms are identified and discussed in detail. Additionally, future perspectives for development of LED light phototherapy are pointed.
... In phototherapy or photodynamic therapy devices, light-emitting diodes (LEDs), capable of generating various wavelengths, have been considered as an alternative light source to fluorescent tube, halogen lamp, and laser beam [3]. LEDs in the visible wavelength (400-600 nm) are applicable as a therapeutic light source to treat skin diseases, cancer cells, and muscle pain because they suppress intercellular signal transduction and metastasis of cancer cells via thermal effects [4,5]. In particular, blue LED irradiation with wavelengths of 400-500 nm has been recently highlighted in various ways, such as to bleach teeth, treat Alzheimer's disease, reduce muscle pain, and ablate cancer cells [5,6]. ...
... LEDs in the visible wavelength (400-600 nm) are applicable as a therapeutic light source to treat skin diseases, cancer cells, and muscle pain because they suppress intercellular signal transduction and metastasis of cancer cells via thermal effects [4,5]. In particular, blue LED irradiation with wavelengths of 400-500 nm has been recently highlighted in various ways, such as to bleach teeth, treat Alzheimer's disease, reduce muscle pain, and ablate cancer cells [5,6]. Moreover, blue LED light has been reported to suppress melanoma and retinal pigment epithelium cells because it generates intracellular oxygen species that can induce apoptosis without any thermal effects [7,8]. ...
... No stimuli were induced in the control group (n = 10) but the other groups were exposed to 460 nm LED or US transducer, and LED combined with the transducer for 30 min up to 3 days. Even though the thermal and mechanical effects caused by 460 nm LED and ultrasound are still under research, LED and ultrasound devices could effectively reduce cancer cell viability with signaling effects to the cells and cavitation effects [5,25]. For LED, light irradiation inhibits the signaling between cancer cells, thus inducing cell death without thermal increments [9]. ...
Light emitting diode (LED) and ultrasound have been powerful treatment stimuli for tumor cell growth due to non-radiation effects. This research is the first preliminary study of tumor cell suppression using a macro-lens-supported 460-nm LED combined with high-frequency ultrasound. The cell density, when exposed to the LED combined with ultrasound, was gradually reduced after 30 min of induction for up to three consecutive days when 48-W DC, 20-cycle, and 50 Vp-p sinusoidal pulses were applied to the LEDs through a designed macro lens and to the ultrasound transducer, respectively. Using a developed macro lens, the non-directional light beam emitted from the LED could be localized to a certain spot, likewise with ultrasound, to avoid additional undesirable thermal effects on the small sized tumor cells. In the experimental results, compared to LED-only induction (14.49 ± 2.73%) and ultrasound-only induction (13.27 ± 2.33%), LED combined with ultrasound induction exhibited the lowest cell density (6.25 ± 1.25%). Therefore, our measurement data demonstrated that a macro-lens-supported 460-nm LED combined with an ultrasound transducer could possibly suppress early stage tumor cells effectively.
... We have investigated the effects of blue light on biological tissues and cells. The reactions induced by blue light mainly involve reactive oxygen species (ROS), which are generated by pigment excitation and cause oxidative stress [9,10]. It has also been reported that the thermal reactions induced by light irradiation cause biological damage [11,12]. ...
... Fortunately, apart from thermal injuries the use of blue light in dental care has not been found to have severe side effects. However, we have reported several negative effects of such light on oral tissues [9,10,40]. We will soon present research data regarding the effects of blue light itself, including its effects on oral tissues. ...
... When dental resin irradiators were held at a distance at which no temperature rise was observed in the target tissue, irradiating light (250 mW/cm 2 ) from a blue halogen light or LED light source still caused a significant reduction in the proliferative activity of gingival fibroblasts. In addition, significant increases in intracellular ROS levels and intracellular mitochondrial disorders were observed [10]. ...
In dentistry, blue light is widely used for tooth bleaching and restoration procedures involving composite resin. In addition, many dentists use magnification loupes to enable them to provide more accurate dental treatment. Therefore, the use of light is indispensable in dental treatment. However, light can cause various toxicities, and thermal injuries caused by light irradiation are regarded as particularly important. In recent years, the eye damage and non-thermal injuries caused by blue light, the so-called “blue light hazard” have gained attention. Unfortunately, much of the research in this field has just begun, but our recent findings demonstrated that blue-light irradiation generates reactive oxygen species (ROS) and induces oxidative stress in oral tissue. However, they also showed that such oxidative stress is inhibited by antioxidants. There have not been any reports that suggested that the ROS-induced phototoxicity associated with blue-light irradiation causes direct clinical damage, but some disorders are caused by the accumulation of ROS. Therefore, it is presumed that it is necessary to suppress the accumulation of oxidative stressors in oral tissues during treatment. In the future, we have to promote discussion about the suppression of phototoxicity in dentistry, including concerning the use of antioxidants to protect against phototoxic damage.
... The absorption spectrum of PpIX includes a maximal peak at 410 nm (Soret band) and four smaller peaks (Q-bands) from 500 to 630 nm 33 . Blue light at wavelengths of 400-500 nm is used for oral treatments such as resin restoration and tooth whitening [34][35][36] . The fluorescence wavelength peak (Fig. 1B) of PpIX excited with blue light (Fig. 1A) was consistent with the fluorescence wavelength for photodynamic diagnoses used in cancer therapy (600-740 nm) 37,38 . ...
... CellROX ® Green Reagent is a cell-permeable reagent used to stain DNA that emits fluorescence in response to oxidative stress. This reagent can stain and be measured in Gram-negative bacteria such as Escherichia coli as well as in mammalian cells 35,45 . The same irradiation protocol and viability measurements were performed with this reagent, and oxidative stress increased during 100J of irradiation (Fig. 5A). ...
... On the other hand, we have already studied blue light irradiation and cytotoxicity within the oral tissues, and determined that taking antioxidants such as N-acetyl-L-cysteine could defend against cytotoxicity, since the antioxidant is maintained in vascular circulation. The antioxidant remains in the blood circulation of the host body and provides the cells and tissues with protection while the oral bacteria remain susceptible with blue light irradiation [34][35][36]39 . Therefore, the antioxidant effect of NAC is not applied to bacteria, applying the NAC might protect the host body tissue and be possible to directly damage a P. gingivalis bactericidal activity by blue light irradiation. ...
The development of antibiotics cannot keep up with the speed of resistance acquired by microorganisms. Recently, the development of antimicrobial photodynamic therapy (aPDT) has been a necessary antimicrobial strategy against antibiotic resistance. Among the wide variety of bacteria found in the oral flora, Porphyromonas gingivalis (P. gingivalis) is one of the etiological agents of periodontal disease. aPDT has been studied for periodontal disease, but has risks of cytotoxicity to normal stained tissue. In this study, we performed aPDT using protoporphyrin IX (PpIX), an intracellular pigment of P. gingivalis, without an external photosensitizer. We confirmed singlet oxygen generation by PpIX in a blue-light irradiation intensity-dependent manner. We discovered that blue-light irradiation on P. gingivalis is potentially bactericidal. The sterilization mechanism seems to be oxidative DNA damage in bacterial cells. Although it is said that no resistant bacteria will emerge using aPDT, the conventional method relies on an added photosensitizer dye. PpIX in P. gingivalis is used in energy production, so aPDT applied to PpIX of P. gingivalis should limit the appearance of resistant bacteria. This approach not only has potential as an effective treatment for new periodontal diseases, but also offers potential antibacterial treatment for multiple drug resistant bacteria.
... Previous studies have shown similar dose-dependence in the cellular consequences of blue light exposure. High intensity blue light for a prolonged time decrease cell growth and increases cell apoptosis in a variety of cell types [30,31]. For example, exposing bone marrow stromal cells (BMSCs) to blue light at an energy density of 12 J/cm 2 for 10 min every day resulted in significant oxidative stress, mitochondrial damage, and apoptosis due to excessive accumulation of ROS. ...
... This increase in cellular resistance to blue light over time may be due to release of antioxidant scavenging enzymes such as catalase and superoxide dismutase (SOD) that neutralize H 2 O 2 production. These highly intriguing findings signify the importance of blue light dosing and may explain why a change in dosing regimen (e.g., expose cells to blue light every day) may not yield the same beneficial outcomes [30,31]. Application of optimal blue light dosing can trigger controlled release of ROS which can in turn activate the cell repair mechanisms, promote development and healing, and augment new bone formation. ...
Blue light–mediated photobiomodulation (PBM) is a promising approach to promote osteogenesis. However, the underlying mechanisms of PBM in osteogenesis are poorly understood. In this study, a human osteosarcoma cell line (i.e., Saos-2 cells) was subjected to intermittent blue light exposure (2500 µM/m²/s, 70 mW/cm², 4.2 J/cm², once every 48 h) and the effects on Saos-2 cell viability, metabolic activity, differentiation, and mineralization were investigated. In addition, this study addressed a possible role of blue light induced cellular oxidative stress as a mechanism for enhanced osteoblast differentiation and mineralization. Results showed that Saos-2 cell viability and metabolic activity were maintained upon blue light exposure compared to unilluminated controls, indicating no negative effects. To the contrary, blue light exposure significantly increased (p < 0.05) alkaline phosphatase activity and Saos-2 cell mediated mineralization. High-performance liquid chromatography (HPLC) assay was used for measurement of reactive oxygen species (ROS) activity and showed a significant increase (p < 0.05) in superoxide (O2•−) and hydrogen peroxide (H2O2) formed after blue light exposure. Together, these results suggest that the beneficial effects of blue light–mediated PBM on osteogenesis may be induced by controlled release of ROS.
... Recently, a detailed descrip on of the process of peroxida on of lipids, which are the main components of the membranes of our cells (Figure 7), has been described and shown to lead to increased cell death within re nal cells, this process involves iron and has thus been called ferroptosis [37] Type II photochemical damage has been studied much more than Type I, for the obvious reason that the studies can be quite short in dura on. This research has shown evidence that short wavelengths of light can cause photochemical damage at the level of molecules [31,38,39], cells [29,[40][41][42][43][44] and ssues [45][46][47] all the way to whole animals [48][49][50][51][52][53][54] including primates [27,55,56] and humans [57][58][59][60][61]. Research in the 1970s looking at the effects of different coloured lasers and their damage to the eye [27,62], showed that short-wavelength light was much more dangerous than longer wavelengths at equal intensi es. Blue light at 440 nm was 20 mes more dangerous than green light at 533 nm [55]. ...
... Effects on re na of ar ficial ligh ng have primarily been based on molecules, cells and ssues all the way to whole animals with a focus on photochemical damage leading to age-related macular degenera on or models thereof [29,31,[38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54]102]. These studies have consistently shown that short wavelength light increases ROS, increases lipid peroxida on, decreases mitochondrial func on and can lead to single stranded cross linking of DNA in nuclear and mitochondrial DNA. ...
In Western societies, people spend as much as 87% of their time indoors under artificial lighting. In the past few decades, the spectral quality of our artificial lighting has changed dramatically as the lighting industry develops more energy efficient lighting that primarily aims to decrease the energy demands and increase the intensity of the specific wavelengths (colours) of light needed for vision. We have seen a widespread increase in the use of fluorescent and phosphorbased
white LED bulbs. These lights often produce too much short wavelength, high energy, violetblue light that contributes to photochemical damage in our skin and eyes over time, and not enough of the mid wavelength, blue-turquoise, light that we need to maintain our circadian (sleep-wake) cycle and alertness, nor the long wavelength red and near infrared (NIR) light that we now know has health benefits (activates melatonin antioxidant production in our mitochondria). Furthermore,
these light sources often have wavelength regions (parts of the colour spectrum) that are relatively lower than would be present under natural sun/skylight conditions. While the primary objective of lighting is to provide adequate light for seeing, recently, we have learned that some of these missing wavelengths and or the balance of different parts of the spectrum have important health benefits
(e.g. blue-turquoise and red/NIR). This is perhaps not surprising since we have evolved under a stable sun/skylight for millions of years.
With this knowledge now available to us, we should take a more precautionary approach whenconsidering the spectral characteristics of lights installed in buildings like schools, offices, homes, and care homes for the elderly, where people may spend more than half of their waking hours. The best option would be a light source that: minimizes the high energy short wavelength violet-blue light, has
a relatively good proportion of blue-turquoise light to keep occupants alert and stimulate their sleepwake cycle, has enough red/NIR to promote good health, and is a close match to sun/skylight to allow for any yet unknown benefits of different parts of the spectrum.
... GFs are commonly used to explore the effects of PBM as a model for periodontitis. In particular, near infra-red (NIR) light has been observed to promote cell proliferation [15][16][17] and decrease markers for inflammation [18][19][20] from GFs. Comparatively, the effects of blue light have only been reported by relatively few authors, where high doses of blue light (> 100 J/cm 2 ) induce increased oxidative stress [21,22]. However, blue light application (405 nm) was also proven effective as red light (635 nm) in promoting gingival fibroblast cell proliferation at 25 J/cm 2 [23]. ...
... The direct application of low-dose blue light on GFs has been assessed by relatively few authors, with PBM at > 100 J/cm 2 being required to induce increased mitochondrial ROS production, accelerated oxidative stress and inhibited cell proliferation [21,22,[58][59][60]. Comparatively, our report now provides new evidence for the biomodulatory effects of low-dose blue light on GFs at < 10 J/cm 2 . ...
Photobiomodulation (PBM) utilises light energy to treat oral disease, periodontitis. However, there remains inconsistency in the reporting of treatment parameters and a lack of knowledge as to how PBM elicits its molecular effects in vitro. Therefore, this study aimed to establish the potential immunomodulatory effects of blue and near infra-red light irradiation on gingival fibroblasts (GFs), a key cell involved in the pathogenesis of periodontitis. GFs were seeded in 96-well plates in media + / − Escherichia coli lipopolysaccharide (LPS 1 μg/ml), or heat-killed Fusobacterium nucleatum ( F. nucleatum, 100:1MOI) or Porphyromonas gingivalis ( P. gingivalis, 500:1MOI). Cultures were incubated overnight and subsequently irradiated using a bespoke radiometrically calibrated LED array (400–830 nm, irradiance: 24 mW/cm ² dose: 5.76 J/cm ² ). Effects of PBM on mitochondrial activity (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and adenosine triphosphate (ATP) assays, total reactive oxygen species production (ROS assay) and pro-inflammatory/cytokine response (interleukin-8 (IL-8) and tumour growth factor-β1 (TGFβ1)) were assessed 24 h post-irradiation. Data were analysed using one-way ANOVA followed by the Tukey test. Irradiation of untreated (no inflammatory stimulus) cultures at 400 nm induced 15%, 27% and 13% increases in MTT, ROS and IL-8 levels, respectively ( p < 0.05). Exposure with 450 nm light following application of P. gingivalis, F. nucleatum or LPS induced significant decreases in TGFβ1 secretion relative to their bacterially stimulated controls ( p < 0.001). Following stimulation with P. gingivalis , 400 nm irradiation induced 14% increases in MTT, respectively, relative to bacteria-stimulated controls ( p < 0.05). These findings could identify important irradiation parameters to enable management of the hyper-inflammatory response characteristic of periodontitis.
... Introduction F ree radicals such as superoxide (O 2 •-), hydroxyl radical ( • OH), nitric oxide are considered to play important roles in various diseases, including acute lung injury, renal disorder with dialysis, and periodontal disease. (1)(2)(3)(4)(5)(6)(7) As controlling inflammation in these pathological states is important, nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used as general therapeutic agents. (8,9) Although much research on NSAIDs and radicals has been conducted, the detailed reaction mechanism of NSAIDs about radical has yet to be clarified. ...
... In conclusion, • DCF might generate via one-electron reduction of DCF in vivo or in human. Furthermore, the generated • DCF might affect the various diseases where DCF is frequently used for treatment, (1)(2)(3)(4)(5)(6)(7) such as inflammation, cancer, or orthopedic disorders. Therefore, it was suggested that our detected • DCF might have important roles in various diseases. ...
Diclofenac, a nonsteroidal anti-inflammatory drug, is commonly used as an antipyretic analgesic owing to its strong anti-inflammatory action in clinical treatment. However, diclofenac can cause injury, with gastrointestinal mucosal lesions and skin photosensitivity as the main side effects. In general, photosensitive drugs contain photosensitive chemical sites, and form free radicals under ultraviolet irradiation, leading to phototoxic reactions. Therefore, this study focuses on free radical production in photosensitive reactions of diclofenac. The free radical production mechanism of diclofenac under ultraviolet irradiation, which might result in photo-toxicity, was clarified using a direct electron spin resonance method. When diclofenac was irradiated with ultraviolet light (254 nm), diclofenac radicals were generated depending on the ultraviolet irradiation time and stably present for 30 min at room temperature. Diclofenac radicals were produced by the ultraviolet irradiation system depending on the dose of diclofenac until 2 mM. Therefore, diclofenac radicals might directly or indirectly react with various biomolecules to cause phototoxicity, other side effects, and new diclofenac pharmacology owing to its stability of diclofenac radicals.
... Thus, all people are globally exposed to different sources of blue light (BL) and for several hours a day. Previously, several studies focused on sight, memory, and sleep; more recently, interest has shifted towards skin aging because it has been shown that long-term exposure to LED-BL radiation disturbs the skin's normal structure causing problems including its premature aging [1,2]. It was reported that a high exposure to LED-BL could accelerate signs of aging, increasing wrinkles, fine lines, dehydration, and hyperpigmentation generally associated with too much sun. ...
... It was reported that a high exposure to LED-BL could accelerate signs of aging, increasing wrinkles, fine lines, dehydration, and hyperpigmentation generally associated with too much sun. Excessive LED-BL exacerbates the oxidation process, which turns in inflammation and alteration of skin barrier, making it more vulnerable to signs of aging [1][2][3][4]. Moreover, increased exposure to LED-BL results in a massive degradation of extracellular matrix (ECM) proteins such as collagen and elastin, produced by imbalance in equilibrium between the accumulation and degradation of ECM components that provide structural and functional support to the skin tissue. ...
The development in digital screen technology has exponentially increased in the last decades, and many of today’s electronic devices use light-emitting diode (LED) technology producing very strong blue light (BL) waves. Long-term exposure at LED-BL seems to have an implication in the dehydration of the epidermis, in the alterations of shape and number of the keratinocytes, and in the aging of the skin. Aquaporins (AQPs) are water membrane channels that permeate both water and glycerol and play an important role in the hydration of epidermis, as well as in proliferation and differentiation of keratinocytes. Thus, we have hypothesized that AQPs could be involved in the aging of the skin exposed to LED-BL. Therefore, we have examined the expression of AQPs in human keratinocytes exposed to LED-BL at dose of 45 J/cm², used as an in vitro model to produce the general features of photo aging of the skin. The aim was to verify if LED-BL induces changes of the basal levels of AQPs. The keratinocytes exposure to LED-BL produced an increase of reactive oxygen species (ROS), an activation of 8-hydroxy-2’-deoxyguanosine (8-OHdG), an alteration of proliferating cell nuclear antigen (PCNA), and a down-regulation of AQP1, 3 and 9. These findings are preliminary evidences that may be used as starting points for further investigations about the mechanistic involvement of AQP1, 3, and 9 in LED-BL-induced skin aging.
... Various lasers can be selected as action lasers for controlling chemical processes in living samples. For example, UV light at 375-405 nm can directly induce reactive oxygen species (ROS) without the need for photosensitizers, serving as a direct laser perturbation to cells or subcellular compartments 48,95,96 . Such ROS generation usually involves the simultaneous presence of endogenous chromophores, oxygen, and photons. ...
Traditional chemical interventions regulate cellular processes but often affect non-target biomolecules. Precise and site-specific control is crucial for studying complex systems. Conventional laser-based methods offer high spatial precision and speed but rely on prior sample knowledge and do not apply to highly mobile targets. Real-time precision opto-control (RPOC) overcomes these limits using closed-loop feedback for automated and signal-determined real-time laser activation to regulate chemical processes in live biological samples. This review compares RPOC with other optical control techniques and explores its advancements, applications, and future directions.
... Bonatti et al. showed that a high irradiance is harmful to fibroblasts [21]. Yoshida et al. used an even higher irradiance (250 mW/cm 2 ) with a lower dose of irradiation (15 J/cm 2 ) on fibroblasts, which resulted in the significant inhibition of metabolic activity and cellular structural changes [22]. In this study, blue light (453 nm) with a low irradiance (10 mW/cm 2 ) led to no inhibition of the CFU of E. coli. ...
Background: Antimicrobial resistance is a problem that threatens the entire world population. Blue light irradiation (BLI) is a novel technology with a bactericidal effect. However, it has only been employed in experimental and preclinical trials. Methods: We employed BLI on four kinds of bacteria (Staphylococcus aureus, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumoniae, and Escherichia coli) and six kinds of artificial implants utilizing a BioLight LED lamp and MEDILIGHT at a 453 nm wavelength. Results: The results showed that the antibacterial effect of BLI enhanced with time and dosage. Irradiation of 165.6 J/cm² corresponding to 120 min of constant mode irradiation, resulted in a significant reduction in the CFU for all four strains. Moreover, the cycling mode (30 s on/30 s off) of the MEDILIGHT prototype showed a more effective microbial effect compared to the constant mode using the BioLight LED lamp. Pseudomonas aeruginosa was the most sensitive strain to BLI, and Staphylococcus aureus showed relatively greater resistance to BLI. BLI showed different antibacterial effects on various types of implants, indicating that different physical properties of artificial implants were more likely to influence the bactericidal effect of BLI. Decreased ATP highlighted energy deprivation after BLI. Genechip analysis of Escherichia coli under constant mode and cycling mode of BLI revealed the downregulation of metabolism-related pathways, and most genes involved in the TCA cycle were downregulated. Conclusions: Our results showed that cycling mode BLI has great potential for use in future disinfection applications. We also proposed a new viewpoint that energy deprivation might be another possible mechanism underlying the antibacterial effect of BLI.
... This different behavior probably depends on the lower metabolic rate of fibroblasts compared to HNSCC cells. On the other hand, some studies have reported the production of blue light-induced reactive oxygen species in gingival fibroblasts' mitochondria and mitochondrial DNA damage in epithelial cells [43]. ...
Simple Summary
The study investigates the effects of curcumin in native conditions and after irradiation with 450 nm light on the energy metabolism, redox balance, and cellular growth of head and neck cancer cells and human primary fibroblasts. Although curcumin in native conditions already shows an anti-cancer effect, affecting energy metabolism and limiting the growth of tumor cells and cells that inhabit the surrounding microenvironment, irradiation with 450 nm light (photodynamic) enhances its effect by acting on antioxidant defenses. This study, therefore, opens up new perspectives on specific wavelengths of light that appear to be able to improve the drug’s action on cancer growth and proliferation, offering hope for better patient outcomes in the future.
Abstract
Oral cancer is the 16th most common malignant tumor worldwide. The risk of recurrence and mortality is high, and the survival rate is low over the following five years. Recent studies have shown that curcumin causes apoptosis in tumor cells by affecting FoF1-ATP synthase (ATP synthase) activity, which, in turn, hinders cell energy production, leading to a loss of cell viability. Additionally, irradiation of curcumin within cells can intensify its detrimental effects on cancer cell viability and proliferation (photodynamic therapy). We treated the OHSU-974 cell line, a model for human head and neck squamous cell carcinoma (HNSCC), and primary human fibroblasts. The treatment involved a 1 h exposure of cells to 0.1, 1.0, and 10 μM curcumin, followed or not by irradiation or the addition of the same concentration of pre-irradiated curcumin. Both instances involved a diode laser with a wavelength of 450 nm (0.25 W, 15 J, 60 s, 1 cm², continuous wave mode). The treatment with non-irradiated 1 and 10 µM curcumin caused ATP synthase inhibition and a consequent reduction in the oxygen consumption rate (OCR) and the ATP/AMP ratio, which was associated with a decrement in lipid peroxidation accumulation and a slight increase in glutathione reductase and catalase activity. By contrast, 60 s curcumin irradiation with 0.25 W—450 nm caused a further oxidative phosphorylation (OxPhos) metabolism impairment that induced an uncoupling between respiration and energy production, leading to increased oxidative damage, a cellular growth and viability reduction, and a cell cycle block in the G1 phase. These effects appeared to be more evident when the curcumin was irradiated after cell incubation. Since cells belonging to the HNSCC microenvironment support tumor development, curcumin’s effects have been analyzed on primary human fibroblasts, and a decrease in cell energy status has been observed with both irradiated and non-irradiated curcumin and an increase in oxidative lipid damage and a slowing of cell growth were observed when the curcumin was irradiated before or after cellular administration. Thus, although curcumin displays an anti-cancer role on OHSU-974 in its native form, photoactivation seems to enhance its effects, making it effective even at low dosages.
... As explained before, LED-light irradiation with wavelengths between 630 and 940 nm does not seem to produce severe harmful effects on humans. However, blue LED light (wavelengths of 400-500 nm) is not exempt from risk and published evidence suggests that blue light has the potential to cause injury to the skin, eyes, and some other human tissues [221][222][223]. ...
Photobiomodulation (PBM) is a procedure that uses light to modulate cellular functions and biological processes. Over the past decades, PBM has gained considerable attention for its potential in various medical applications due to its non-invasive nature and minimal side effects. We conducted a narrative review including articles about photobiomodulation, LED light therapy or low-level laser therapy and their applications on dermatology published over the last 6 years, encompassing research studies, clinical trials, and technological developments. This review highlights the mechanisms of action underlying PBM, including the interaction with cellular chromophores and the activation of intracellular signaling pathways. The evidence from clinical trials and experimental studies to evaluate the efficacy of PBM in clinical practice is summarized with a special emphasis on dermatology. Furthermore, advancements in PBM technology, such as novel light sources and treatment protocols, are discussed in the context of optimizing therapeutic outcomes and improving patient care. This narrative review underscores the promising role of PBM as a non-invasive therapeutic approach with broad clinical applicability. Despite the need for further research to develop standard protocols, PBM holds great potential for addressing a wide range of medical conditions and enhancing patient outcomes in modern healthcare practice.
... For the control samples, treatment with PS is omitted. The ROS production rate, expressed as arbitrary fluorescence units, was measured using ImageJ software [81,82]. ...
Photodynamic therapy (PDT) is a minimally invasive treatment that uses the combination of a photosensitizing agent (PS) and light to selectively target solid tumors, as well as several non-neoplastic proliferating cell diseases. After systemic administration, PSs are activated by localized irradiation with visible light; in the presence of adequate concentrations of molecular oxygen, this causes the formation of reactive oxygen species (ROS) and subsequent tissue damage. In this study, two series of tetrakis(N-alkylpyridinium-4-yl)porphyrins were synthesized, differing in the presence or absence of a zinc ion in the tetrapyrrole nucleus, as well as in the N-alkyl chain length (from one to twelve carbon atoms). The compounds were chemically characterized, and their effect on cell viability was evaluated using a panel of three tumor cell lines to determine a possible relationship between photodynamic activity and Zn presence/alkyl chain length. The types of cell death mechanisms involved in the effect of the various PSs were also evaluated. The obtained results indicate that the most effective porphyrin is the Zn-porphyrin, with a pendant made up of eight carbon atoms (Zn-C8).
... Olympus IX81 fluorescence microscopy, camera connected, was used to detect the production of ROS (Ex: 488 nm; Em: 520 nm). The ROS production rate, expressed as a.u. of fluorescence, was measured with ImageJ software [81]. ...
Photodynamic therapy (PDT) relies on the combined action of a photosensitizer (PS), light at an appropriate wavelength, and oxygen, to produce reactive oxygen species (ROS) that lead to cell death. However, this therapeutic modality presents some limitations, such as the poor water solubility of PSs and their limited selectivity. To overcome these problems, research has exploited nanoparticles (NPs). This project aimed to synthesize a PS, belonging to the BODIPY family, covalently link it to two NPs that differ in their lipophilic character, and then evaluate their photodynamic activity on SKOV3 and MCF7 tumor cell lines. Physicochemical analyses demonstrated that both NPs are suitable for PDT, as they are resistant to photobleaching and have good singlet oxygen (¹O2) production. In vitro biological analyses showed that BODIPY has greater photodynamic activity in the free form than its NP-bounded counterpart, probably due to greater cellular uptake. To evaluate the main mechanisms involved in PDT-induced cell death, flow cytometric analyses were performed and showed that free BODIPY mainly induced necrosis, while once bound to NP, it seemed to prefer apoptosis. A scratch wound healing test indicated that all compounds partially inhibited cellular migration of SKOV3 cells.
... Mitochondrial targeting exogenous antioxidant (mito-TEMPO) or manganese superoxide dismutase (MnSOD) transfection can inhibit mitochondrial ROS generation, and prevent the increase of IL-1, IL-6 and TNF-α [40,68]. Of great significance for dental clinical operations, dental resin composites (mainly TEGDMA components), blue light irradiation (for resin restoration, bleaching, etc., within 5 min) have also been shown to cause oxidative stress in hGFs by inducing mitochondrial ROS generation [69,70]. ...
Periodontitis is a chronic infectious disorder damaging periodontal tissues, including the gingiva, periodontal ligament, cementum, and alveolar bone. It arises from the complex interplay between pathogenic oral bacteria and host immune response. Contrary to the previous view of “energy factories”, mitochondria have recently been recognized as semi-autonomous organelles that fine-tune cell survival, death, metabolism, and other functions. Under physiological conditions, periodontal tissue cells participate in dynamic processes, including differentiation, mineralization, and regeneration. These fundamental activities depend on properly functioning mitochondria, which play a crucial role through bioenergetics, dynamics, mitophagy, and quality control. However, during the initiation and progression of periodontitis, mitochondrial quality control is compromised due to a range of challenges, such as bacterial–host interactions, inflammation, and oxidative stress. Currently, mounting evidence suggests that mitochondria dysfunction serves as a common pathological mechanism linking periodontitis with systemic conditions like type II diabetes, obesity, and cardiovascular diseases. Therefore, targeting mitochondria to intervene in periodontitis and multiple associated systemic diseases holds great therapeutic potential. This review provides advanced insights into the interplay between mitochondria, periodontitis, and associated systemic diseases. Moreover, we emphasize the significance of diverse therapeutic modulators and signaling pathways that regulate mitochondrial function in periodontal and systemic cells.
... In general, it has been suggested that the cytotoxicity of LEDs is related to the increase of cell apoptosis, production of reactive oxygen species (ROS), lipid peroxidation and DNA damage 3,55 . Mitochondria have also been identified as a target for the toxicity of LED illumination 15,23,56,57 , which could be related to the induction of apoptosis. It is known that the mitochondria, a fundamental organelle for maintaining vital cellular functions, also plays a key role in cell death through the regulation of cytochromes 58,59 , intracellular Ca 2+ concentration 59 , reactive oxygen species (ROS) 60-62 , transmembrane mitochondrial potential 63 , mitochondrial transition pores by caspases or ATP depletion 62 , changes in the redox state metabolism 64 and cyclosporine Asensitive mitochondrial permeability transition 62 . ...
Introduction the use of light emitting diodes (LED) in domestic and public vias have increased in the last 20 years. In addition, the LED light has been used as a light source for medical applications. Objective since humans are increasingly exposed to LEDs, there is an urgency to investigate the possible biological effects on tissues caused by this exposure. So, researchers have been focused their investigations in the application of this light in the health field. Material and method in this review, a search in important databases was performed on the biological effects caused after application of different LED light protocols in in vitro and in vivo studies. Result although most published papers have shown positive results, some of them reported negative biological effects of light LEDs technology on humans’ cells/tissues. Conclusion therefore, the comprehension of the biological effects caused by light LEDs will provide a better assessment of the risks involved using this technology.
... Внесение в питательную среду тушителя синглетного кислорода азида натрия лишь частично снижало фотобиологический эффект. Участие АФК в процессах, лежащих в основе инактивирующего действия синего света в отношении соматических клеток, отмечалось и ранее (см., например, [16,35,36,[39][40][41]). Среди указанных АФК, зарегистрированных различными методами в клетках при воздействии синего света,синглетный кислород, супероксиданионрадикал, гидроксильный радикал, перекись водорода и др. ...
... The photostress effect of blue light has been studied extensively for aerobic microbes and pluricellular organisms. 34,44,45 It relies on an O 2 -dependent mechanism where blue light excites photosensitizing chromophores endogenous to the cells such as porphyrins, (ribo)avins, and their derivatives. These photoresponsive molecules then cause the generation of toxic ROS damaging cells. ...
Illuminated semiconductors stimulate CO2 bioconversion by acetogens and other autotrophic microorganisms. Visible light by itself is known to alter the lifestyle of non-photosynthetic aerobic microbes via photoexcitation stress. The direct...
... Referring to the photobiological safety standard proposed by the International Electrotechnical Commission (IEC), the monochromatic light in the range of 435 to 440 nm has the most serious blue-light hazard (BLH) on the retina [4]. Overexposure to blue light promotes the production of reactive oxygen species (ROS), then damages the retinal cells by oxidative stress and inflammatory response [5][6][7][8][9]. Exposure to bluelight or blue-enriched white LED also results in the loss of photoreceptors, lipid peroxidation, as well as the autophagy and apoptosis of retinal cells [5,7,10,11]. ...
The blue-light hazard (BLH) has raised concerns with the increasing applications of white light-emitting diodes (LEDs). Many researchers believed that the shorter wavelength or more light components generally resulted in more severe retinal damage. In this study, based on the conventional phosphor-coated white LED, we added azure (484 nm), cyan (511 nm), and red (664 nm) light to fabricate the low-hazard light source. The low-hazard light sources and conventional white LED illuminated 68 Sprague-Dawley (SD) rats for 7 days. Before and after light exposure, we measured the retinal function, thickness of retinal layers, and fundus photographs. The expression levels of autophagy-related proteins and the activities of oxidation-related biochemical indicators were also measured to investigate the mechanisms of damaging or protecting the retina. With the same correlated color temperature (CCT), the low-hazard light source results in significantly less damage on the retinal function and photoreceptors, even if it has two times illuminance and blue-light hazard-weighted irradiance ([Formula: see text]) than conventional white LED. The results illustrated that [Formula: see text] proposed by IEC 62471 could not exactly evaluate the light damage on rats' retinas. We also figured out that more light components could result in less light damage, which provided evidence for the photobiomodulation (PBM) and spectral opponency on light damage.
... Most recently, blue light was increasingly used in the biomedical field, while the risk of overdose exposure also attracted attention. Besides thermal damage [43] and ROS-induced DNA damage [44], cell death might be attributed to the free radicals released during photopolymerisation [45] and the leaching of unpolymerised residual monomers in the microenvironment [46]. Nevertheless, no significant relationship between cytotoxicity and irradiation time was found in the study, indicating that the harmful byproducts during free-radical polymerisation of hydrogels could be kept at a safe level. ...
Inflammation and trauma destroy the tooth-supporting tissue, leading to the loss of oral function and the difficulty of denture restoration. Guided tissue regeneration (GTR) is a technique based on a barrier membrane designed to restrict soft tissue invasion and maintain the space for bone regeneration. This study examined a new formulation to prepare methacrylated carboxymethyl chitosan (CMCS-MA) hydrogel as a barrier membrane that could be crosslinked under visible-light irradiation. This new CMCS-MA hydrogel showed fast light-curing, good biocompatibility, and could be degraded by lysozyme. Further, the physicochemical property, cytotoxicity and antibacterial activity of the CMCS-MA hydrogels can be adjusted by varying the degree of substitution of methacrylic acid (DS) in a certain range. Thus, the biocompatible and biodegradable CMCS-MA hydrogels may have a promising application in periodontal tissue regeneration with convenience and flexibility.
... However, compared to ultraviolet light, visible light may be harmless to living organisms, and its effect on healthy tissues has not been extensively examined [7]. Some studies have reported that ROS and reactive nitrogen species (RNS) are produced in response to PBM [8]. ROS are produced in response to large doses of light, particularly blue light [9,10]. ...
Simple Summary
Photobiomodulation studies have reported that blue light irradiation induces the production of reactive oxygen species. We examined the effect of blue laser (405 nm) irradiation on ATP level in the skin and measured the types of reactive oxygen species and reactive nitrogen species. The decrease in the skin ATP level due to blue light irradiation may be caused by oxidative stress due to the generation of reactive oxygen species. These findings highlight the need to consider the effects on the skin when performing photobiomodulation treatment using blue light.
Abstract
Photobiomodulation studies have reported that blue light irradiation induces the production of reactive oxygen species. We investigated the effect of blue laser (405 nm) irradiation on the ATP levels in mouse skin and determined the types of reactive oxygen species and reactive nitrogen species using cultured mouse fibroblasts. Blue laser irradiation caused a decrease in the ATP level in the mouse skin and triggered the generation of superoxide anion and hypochlorous acid, whereas nitric oxide and peroxynitrite were not detected. Moreover, blue laser irradiation resulted in reduced cell viability. It is believed that the decrease in the skin ATP level due to blue light irradiation results from the increased levels of oxidative stress due to the generation of reactive oxygen species. This method of systematically measuring the levels of reactive oxygen species and reactive nitrogen species may be useful for understanding the effects of irradiation conditions.
... Previous studies have shown that various level of light exposing would cause different biological signi cance [1][2][3]. Recent reports uncovered that LED treatment could meaningfully ameliorate lung in ammation, inhibit human gingival broblast cell proliferation and facilitate Post-surgical recovery and wound healing [4][5][6][7]. Notable among the various species of LED is that blue LED with 430-490 nm wavelengths showed excelent antitumor activity in vitro and in vivo experiments. Blue light could effectively inhibit the tumor progress of skin tumors, melanoma, leukemia, colon cancer mainly depending on the accumulation of intracellular reactive oxygen species (ROS) [8][9][10][11]. ...
Phototherapies, including sunlight, infrared, ultraviolet, visible and laser, parts of which present high curative effect, small invasion, and negligible adverse reactions in cancer treatment. Here we aimed to explore the potential therapeutical effects of blue LED in hepatoma cell and decipher the underlying cellular/molecular mechanisms. We demonstrated that the irradiation of blue LED light in hepatoma cell could lead to cell proliferation reduction along with the cell apoptosis increase. Simultaneously, blue LED irradiation also markedly suppressed the migration and invasion ability of hepatoma cells. Sphere formation analysis further revealed the decreased stemness of hepatoma cell under the treatment of blue LED irradiation. In addition, blue LED irradiation significantly promoted the expression of γ-H2AX, a sensitive molecular marker of DNA damage. Collectively, we demonstrated that blue LED irradiation exhibited anti-tumor effects on liver cancer by inducing DNA damage, representing a potential approach for human hepatoma treatment.
... In line with the study performed by Zeng et al.120 , who assessed intracellular ROS generation in mouse dermal fibroblasts after UVB irradiation, the H 2 O 2 concentration reached its maximum at 30 minutes and was normalized at 1 hour after irradiation. Thus, the well-known effect of increased ROS levels by blue light was confirmed77,85,89 . However, contrary to the assumption that higher irradiation doses correlate with elevated ROS levels 121 , a higher H 2 O 2 peak was found directly after blue light treatment with the lower dose of 5.4 J/cm 2 . ...
Phototherapy, basically heliotherapy, has already been used for the last 3,000 years. However, major breakthroughs in modern clinical phototherapy were achieved since the beginning of the 20th century, including for instance the invention of lasers. From then on, the use of light as a therapeutic tool grew constantly, demonstrated by the development of new artificial light sources and an increasing number of published studies on a variety of medical, mostly cutaneous, disorders. But although the last decade has witnessed a rapid expansion of photobiomodulation, its scientific acceptance is still debated: first, due to inconsistent experimental outcomes, caused by highly variable study designs and irradiation parameters, and second, due to a lack of mechanistic insights into light-triggered signaling. The latter especially applies for blue light, which is, in comparison to red and (near-)infrared light, rather used for a limited range of medical cutaneous ailments, primarily necessitating inhibitory or even cytotoxic effects, like fibrotic skin diseases. However, also stimulatory effects of blue light have rarely been reported in wound healing studies. Hence, the biomodulatory potential of different blue light doses on cellular activity was examined using primary normal human dermal fibroblasts, NHDF cells, in particular with respect to metabolic processes, cell proliferation and transcriptome changes. Photobiomodulation using blue light revealed dose-dependent effects on the metabolism of NHDF cells, with low doses resulting in an increased activity, whereas higher irradiation doses induced a decreased and therefore inhibited cell metabolism. Based on the biphasic response, two irradiation doses, each leading to the maximum effect in the respective phase, were selected: 5.4 J/cm² and 21.6 J/cm². Cell metabolism assays performed at different time points after irradiation with either 5.4 J/cm² or 21.6 J/cm², revealed a fast response following the lower dose, while the higher one led to a delayed onset of metabolic inhibition. Nevertheless, both, stimulation and inhibition of cellular metabolism were long-lasting until 24 hours after light treatment. Subsequent studies with repeated irradiations on consecutive days, imitating a 'chronic' exposure model, showed an enhanced inhibition following multiple treatments using 21.6 J/cm² of blue light, whereas two daily treatments over several days were required for an increased stimulation by 5.4 J/cm² of blue light. The contrary effects on cell metabolism observed for both irradiation doses, were translated into similar, but less pronounced effects in proliferation, which was studied with various assays testing cell cycle distribution, DNA synthesis and cell counts. Also gene expression profiles revealed contrary trends in DNA replication and cell cycle regulation affecting cyclins, CDKs as well as repair checkpoints. Mitochondrial function was assessed by measuring H₂O₂ concentrations and ΔΨm at different time points following irradiation. Both blue light doses revealed a rapid increase of H₂O₂ levels, accompanied by fast decreases in ΔΨm indicating metabolic stress; however, both effects returned towards control levels within 24 hours. Thus, to some extent, light effects were identified to rely on retrograde mitochondrial signaling altering the expression of several transcription factors like NF-κB or Nrf2 via changes in ΔΨm and the Janus-face mediator ROS. Moreover, PRKAA1 and AKT1 coding for primary effectors of metabolic stress, respectively AMPK and AKT, were found significantly expressed exerting antagonistic regulations of FOXO1 and MTOR, which modulate oxidative stress resistance, cell survival and growth. In addition, genes involved in antioxidant defense mechanisms, inter alia transcribed by Nrf2 and AhR, were found up-regulated, showing a higher activation for 21.6 J/cm². Cytoprotection was further promoted by affecting the interplay between pro- and anti-apoptotic genes inducing stress resistance and even a higher proliferative capacity following 5.4 J/cm² of blue light. Prevention of apoptotic signaling was verified by cell viability studies negating cytotoxicity up to a single light dose of 172.8 J/cm². Though, reduced proliferation rates observed after consecutive irradiations with 21.6 J/cm² each were accompanied by a higher occurrence of apoptotic cells, possibly indicating mitotic catastrophe. In conclusion, blue light seemed to be pro-oxidant in the short term, but anti-oxidant in the long term likely to induce stress resistance, at least following low and controlled amounts of oxidative stress. Driven by metabolic and redox homeostasis, various downstream processes were activated modifying antioxidant defense, survival and proliferation. Moreover, the results indicated that an optimal choice of irradiation parameters, particularly the dose, is important for the effectiveness of the treatment, since doses lower or higher than the optimum can lead to ineffective or even negative outcomes. Using cycled irradiation, the differential effect of blue light doses on NHDF cells might be exploited for novel concepts in advanced wound care, particularly for chronic wounds showing impaired activity of dividing cells and fibrotic skin diseases.
... Midieron la tasa de proliferación y el estrés oxidativo (producción especies reactivas de oxigeno ROS), hallaron que tras exposición de 5 min con LED se tenía reducción significativa de la proliferación comparado a fuente halógena, en ambas fuentes se detectó daños en las mitocondrias después de 24 horas de ser expuestas y ambas fuentes comparadas a control no expuesto incrementaban la producción de ROS intracelular de manera significativa. 19 Estos hallazgos son de relevancia y recomiendan aislar los tejidos blandos con resinas de color y grosor suficiente para reflejar la luz azul. Se puede ver resumido los principales detalles de estos trabajos en la Tabla 1 de extracción de datos. ...
RESUMENDiversos estudios clínicos han evaluado la efectividad a corto y largo plazo de los agentes de aclaramiento dental a base de peróxido de hidrogeno (PH), igualmente sus efectos adversos sobre los tejidos duros y blandos, encontrando que la sensibilidad dental y gingival son los más frecuentes, y generalmente son efectos leves y de naturaleza transitoria. Sin embargo, estos estudios solo se basan en observaciones clínicas y percepción de los pacientes. El propósito de esta revisión de tema es describir, basado en la evidencia científica in vitro e in vivo, los principales efectos adversos generados por el PH sobre los tejidos periodontales y sus poblaciones celulares, extrayendo las principales relevancias clínicas que aporten al profesional consejos útiles a la hora de seleccionar y establecer protocolos de manejo clínico en los pacientes que demanden este tipo de tratamiento, procurando reducir injurias a los tejidos de soporte periodontal. Podemos concluir que el uso de estos agentes químicos, aunque siguen generando efectos inmediatos indeseables como la sensibilidad dental e irritación gingival, y basados en la relación dosis-tiempo de exposición, constituyen un tratamiento seguro. No obstante, no se deben subestimar los efectos dañinos potenciales que puede llegar a producir su uso indebido, de allí la importancia de conocer su composición química y los efectos sobre las estructuras que se aplican, y partiendo siempre de una salud dental y periodontal para su aplicación.
... This study showed that 30 minutes irradiation with 465-nm blue LED inhibited the growth of human colon cancer cell lines, and blue LED-induced autophagy was shown to be the mechanism of cell growth inhibition. Additionally, the effects of LED were inhibited by Blue LED have been reported to have phototoxic and antiproliferative effects through the generation of intracellular reactive oxygen species (ROS); 15,16 blue LED irradiation has also been reported to induce apoptosis by a mitochondrially mediated signaling pathway that reduces early-stage melanoma growth. 6 Recently, we reported that 10 min/d 9 5 d of blue LED irradiation induced apoptosis in colon cancer cells. ...
Background
Light emitting‐diodes (LED) have various effects on living organisms and recent studies have shown the efficacy of visible light irradiation from LED for anticancer therapies. However, the mechanism of LED's effects on cancer cells remains unclear. The aim of the present study was to investigate the effects of LED on colon cancer cell lines and the role of photoreceptor Opsin 3 (Opn3) on LED irradiation in vitro.
Methods
Human colon cancer cells (HT‐29 or HCT‐116) were seeded onto laboratory dishes and irradiated with 465‐nm LED at 30 mW/cm² for 30 minutes. Cell Counting Kit‐8 was used to measure cell viability, and apoptosis and caspase 3/8 expression were evaluated by AnnexinV/PI and reverse transcription‐polymerase chain reaction (RT‐PCR), respectively. Autophagy and expression of LC‐3 and beclin‐1 were also evaluated by autophagy assays, RT‐PCR and Western blotting. We further tested Opn3 knockdown by Opn3 siRNA and the Gi/o G‐protein inhibitor NF023 in these assays.
Results
Viability of HT‐29 and HCT‐116 cells was lower in 465‐nm LED‐irradiated cultures than in control cultures. LC‐3 and beclin‐1 expressions were significantly higher in LED‐irradiated cultures, and autophagosomes were detected in irradiated cells. The reductive effect of cancer cell viability following blue LED irradiation was reversed by Opn3 knockdown or NF023 treatment. Furthermore, increased LC‐3 and beclin‐1 expression that resulted from blue LED irradiation was suppressed by Opn3 knockdown or NF023 treatment.
Conclusion
Blue LED irradiation suppressed the growth of colon cancer cells and Opn3 may play an important role as a photoreceptor.
... Light with a wavelength of 400-500 nm, previously applied to photo-activated resin composite systems, is also used to activate dental bleaching gels. However, this visible light may cause injury to the tissues due to ROS production via light irradiation [26]. Furthermore, the increase in the pulp temperature was reported after the use of halogen light, LED, or laser [25,27]. ...
Objectives
This systematic review (PROSPERO register: CRD42016053140) investigated the influence of different types of light on the pulp tissue during dental bleaching. Materials and methodsTwo independent authors conducted a systematic search and risk of bias evaluations. An electronic search was undertaken (PubMed/Medline, Embase, The Cochrane Library, and other databases) until May 2017. The population, intervention, comparison, outcomes (PICO) question was: “Does the light in dental bleaching change the response of the pulp to the bleaching procedure?” The intervention involved pulp tissue/cells after bleaching with light, while the comparison involved pulp tissue/cells after bleaching without light. The primary outcome was the inflammation/cytotoxicity observed in pulp after bleaching. ResultsOut of 2210 articles found, 12 articles were included in the review; four were in vivo studies (one study in dogs/others in human), and eight were in vitro studies (cell culture/with artificial pulp chamber or not). The light source used was halogen, light-emitting diode (LED), and laser. Only one in vivo study that used heat to simulate light effects showed significant pulp inflammation. Only two in vitro studies demonstrated that light influenced cell metabolism; one using halogen light indicated negative effects, and the other using laser therapy indicated positive effects. Given that animal and in vitro studies have been identified, there remain some limitations for extrapolation to the human situation. Furthermore, different light parameters were used. Conclusions
The effects of dental bleaching on the pulp are not influenced by different types of light, but different light parameters can influence these properties. Clinical relevanceThere is insufficient evidence about the influence of different types of light on inflammation/cytotoxicity of the pulp.
... generally considered to be toxic to healthy cells [22]. For instance, Yoshida et al. [44] showed that blue light (460 nm) inhibits human gingival fibroblast proliferation by inducing reactive oxygen species (ROS) production in mitochondria. ...
Background and objective:
Low-level laser irradiation (LLLI) exerts various biostimulative effects, including promotion of wound healing and bone formation; however, few studies have examined biostimulation using blue lasers. The purpose of this study was to investigate the effects of low-level ultrahigh-frequency (UHF) and ultrashort-pulse (USP) blue laser irradiation on osteoblasts.
Study design/ materials and methods:
The MC3T3-E1 osteoblast cell line was used in this study. Following LLLI with a 405 nm newly developed UHF-USP blue laser (80 MHz, 100 fs), osteoblast proliferation, and alkaline phosphatase (ALP) activity were assessed. In addition, mRNA levels of the osteoblast differentiation markers, runt-related transcription factor 2 (Runx2), osterix (Osx), alkaline phosphatase (Alp), and osteopontin (Opn) was evaluated, and extracellular calcification was quantified. To clarify the involvement of transient receptor potential (TRP) channels in LLLI-induced biostimulation, cells were treated prior to LLLI with capsazepine (CPZ), a selective inhibitor of TRP vanilloid 1 (TRPV1), and subsequent proliferation and ALP activity were measured.
Results:
LLLI with the 405 nm UHF-USP blue laser significantly enhanced cell proliferation and ALP activity, compared with the non-irradiated control and LLLI using continuous-wave mode, without significant temperature elevation. LLLI promoted osteoblast proliferation in a dose-dependent manner up to 9.4 J/cm2 and significantly accelerated cell proliferation in in vitro wound healing assay. ALP activity was significantly enhanced at doses up to 5.6 J/cm2 , and expression of Osx and Alp mRNAs was significantly increased compared to that of the control on days 3 and 7 following LLLI at 5.6 J/cm2 . The extent of extracellular calcification was also significantly higher as a result of LLLI 3 weeks after the treatment. Measurement of TRPV1 protein expression on 0, 3, and 7 days post-irradiation revealed no differences between the LLLI and control groups; however, promotion of cell proliferation and ALP activity by LLLI was significantly inhibited by CPZ.
Conclusion:
LLLI with a 405 nm UHF-USP blue laser enhances extracellular calcification of osteoblasts by upregulating proliferation and differentiation via TRPV1. Lasers Surg. Med. © 2017 Wiley Periodicals, Inc.
... Blue light also exhibited effects on human gingival fibroblasts in vitro (Yoshida et al., 2013). After 5 min blue light (460 nm) irradiation at an irradiance of 372.3 mW/cm 2 (or 111.7 J/cm 2 ), cell-proliferation activity decreased by approximately 45%, intracellular ROS increased by approximately 60%. ...
... Blue light also exhibited effects on human gingival fibroblasts in vitro (Yoshida et al., 2013). After 5 min blue light (460 nm) irradiation at an irradiance of 372.3 mW/cm 2 (or 111.7 J/cm 2 ), cell-proliferation activity decreased by approximately 45%, intracellular ROS increased by approximately 60%. ...
As an innovative non-antibiotic approach, antimicrobial blue light in the spectrum of 400-470 nm has demonstrated its intrinsic antimicrobial properties resulting from the presence of endogenous photosensitizing chromophores in pathogenic microbes and, subsequently, its promise as a counteracter of antibiotic resistance. Since we published our last review of antimicrobial blue light in 2012, there have been a substantial number of new studies reported in this area. Here we provide an updated overview of the findings from the new studies over the past 5 years, including the efficacy of antimicrobial blue light inactivation of different microbes, its mechanism of action, synergism of antimicrobial blue light with other angents, its effect on host cells and tissues, the potential development of resistance to antimicrobial blue light by microbes, and a novel interstitial delivery approach of antimicrobial blue light. The potential new applications of antimicrobial blue light are also discussed.
... 159 Blue LEDs can also generate ROS more effectively than quartz tungsten halogen light effectively thus, inhibiting human gingival fibroblast cellular proliferation. 160 Similarly, in another dental application, a 630 nm LED light was also proven as an effective transdentinal penetration, enabling the stimulation of pulp cell metabolism which is vital in pulp regeneration. 161 Furthermore, the ability of LED to impart phototoxic and anti-bacterial action was made possible through mitochondrial apoptotic pathway. ...
Searching for narrow-band red-emitting and thermally stable phosphors is the ultimate strategy toward enhanced performance of phosphor converted light emitting diodes (pc-LED). The red emission is assured by the nitride host because of its relatively more covalent character than oxides and sulfides; however, the narrow emission is attributed to crystallographic, morphological, and electronic considerations. The symmetric coordination site ensures equal ligand effect in all direction fits well with the configuration of Eu²⁺ f orbitals in the excited state, as observed in cuboid nitrides. Further, thermal stability is ascribed not only to suitable bandgap butmore specifically, a relatively distant location of the lowest 5d level from the bottom of the conduction band (CB) that consequently entails high energy to quench excited electrons by exciting them further up to the CB. Modes toward the development of new nitride hosts with potentially narrow-band emission have been identified. A viewpoint on light-emitting diode (LED), backlighting, and laser lighting, which remains the most economically-rewarding phosphors application, is presented. Other exciting frontiers, such as agricultural illumination and persistent luminescence, maximize nitride systems that have other properties other than the stringent narrow-band red emission and excellent thermal stability required for the desired improvement of the mainstream LED application.
... In addition, blue LED þ HFFU demonstrated the reduced cell density up to 3 days post stimulus induction, compared to other experimental groups. Yoshida et al. [21] demonstrated that blue LED can induce thermal effects in mitochondria which are time-dependent. Blue LED leads to cell death and inhibition of tumor cell growth [22]. ...
Purpose:
Light sources such as laser and light emitting diode or ultrasound devices have been widely used for cancer therapy and regenerative medicines, since they are more cost-effective and less harmful than radiation therapy, chemotherapy or magnetic treatment. Compared to laser and low intensity ultrasound techniques, light emitting diode and high frequency focused ultrasound shows enhanced therapeutic effects, especially for small tumors.
Materials and methods:
We propose combinational light emitting diode-high frequency focused ultrasound treatment for human cervical cancer HeLa cells. Individual red, green, and blue light emitting diode light only, high frequency focused ultrasound only, or light emitting diode light combined with high frequency focused ultrasound treatments were applied in order to characterize the responses of HeLa cells.
Results:
Cell density exposed by blue light emitting diode light combined with high frequency focused ultrasound (2.19 ± 0.58%) was much lower than that of cells exposed by red and green light emitting diode lights (81.71 ± 9.92% and 61.81 ± 4.09%), blue light emitting diode light (11.19 ± 2.51%) or high frequency focused ultrasound only (9.72 ± 1.04%).
Conclusions:
We believe that the proposed combinational blue light emitting diode-high frequency focused ultrasound treatment could have therapeutic benefits to alleviate cancer cell proliferation.
... Most of the studies however do agree that the overall effect of blue light PBM is to increase the level of cellular ROS. This ROS increase is likely to inhibit proliferation in many cases 14,15 , and can even produce apoptosis and outrightcytotoxicity if the doses are high enough 16,17 . However matters are complicated by the fact that the term "blue light" has been used to refer to wavelengths spanning a range of over 100 nm. ...
We previously showed that blue (415 nm) and green (540 nm) wavelengths were more effective in stimulating osteoblast differentiation of human adipose-derived stem cells (hASC), compared to red (660 nm) and near-infrared (NIR, 810 nm). Intracellular calcium was higher after blue/green, and could be inhibited by the ion channel blocker, capsazepine. In the present study we asked what was the effect of these four wavelengths on proliferation of the hASC? When cultured in proliferation medium there was a clear difference between blue/green which inhibited proliferation and red/NIR which stimulated proliferation, all at 3 J/cm². Blue/green reduced cellular ATP, while red/NIR increased ATP in a biphasic manner. Blue/green produced a bigger increase in intracellular calcium and reactive oxygen species (ROS). Blue/green reduced mitochondrial membrane potential (MMP) and lowered intracellular pH, while red/NIR had the opposite effect. Transient receptor potential vanilloid 1 (TRPV1) ion channel was expressed in hADSC, and the TRPV1 ligand capsaicin (5uM) stimulated proliferation, which could be abrogated by capsazepine. The inhibition of proliferation caused by blue/green could also be abrogated by capsazepine, and by the antioxidant, N-acetylcysteine. The data suggest that blue/green light inhibits proliferation by activating TRPV1, and increasing calcium and ROS.
... Taken together, most studies have found that blue light generates reactive oxygen species [47,[76][77][78][79], bioactive nitric oxide [42,70,72] and lead to G protein coupled signaling via melanopsin ( Table 1). Nonetheless, it is unclear and controversially discussed which is the dominant process, as conflicting results have been published. ...
Background
Visible light is absorbed by photoacceptors in pigmented and non-pigmented mammalian cells, activating signaling cascades and downstream mechanisms that lead to the modulation of cellular processes. Most studies have investigated the molecular mechanisms and therapeutic applications of UV and the red to near infrared regions of the visible spectrum. Considerably less effort has been dedicated to the blue, UV-free part of the spectrum.
Objective
In this review, we discuss the current advances in the understanding of the molecular photoacceptors, signaling mechanisms, and corresponding therapeutic opportunities of blue light photoreception in non-visual mammalian cells in the context of inflammatory skin conditions.
Methods
The literature was scanned for peer-reviewed articles focusing on the molecular mechanisms, cellular effects, and therapeutic applications of blue light.
Results
At a molecular level, blue light is absorbed by flavins, porphyrins, nitrosated proteins, and opsins; inducing the generation of ROS, nitric oxide release, and the activation of G protein coupled signaling. Limited and contrasting results have been reported on the cellular effects of blue light induced signaling. Some investigations describe a regulation of proliferation and differentiation or a modulation of inflammatory parameters; others show growth inhibition and apoptosis. Regardless of the elusive underlying mechanism, clinical studies show that blue light is beneficial in the treatment of inflammatory skin conditions.
Conclusion
To strengthen the use of blue light for therapeutic purposes, further in depth studies are clearly needed with regard to its underlying molecular and cellular mechanisms, and their translation into clinical applications.
... Meanwhile visible light has also been studied to directly treat dermatitis and muscle analgesia, as well as to remove bacteria in vitro [124][125][126]. Recent studies reported that blue LEDs, via generation of intracellular reactive oxygen species, are more effective than quartz tungsten halogen (QTH) lamps in inhibiting the proliferation of human gingival fibroblast cells [127]. Especially, a recent study of the phototoxic and bactericidal effect of blue LED irradiation revealed that LED irradiation induces apoptosis by activating a mitochondria-mediated pathway and reducing the initial growth rate of melanoma cells, which indicates that the potential of LEDs will be far greater than expected [128,129]. ...
About twenty years ago, in the autumn of 1996, the first white light-emitting diodes (LEDs) were offered for sale. These then-new devices ushered in a new era in lighting by displacing lower-efficiency conventional light sources including Edison's venerable incandescent lamp as well as the Hg-discharge-based fluorescent lamp. We review the history of the conception, improvement, and commercialization of the white LED. Early models of white LEDs already exceeded the efficiency of low-wattage incandescent lamps, and extraordinary progress has been made during the last 20 years. The review also includes a discussion of advances in blue LED chips, device architecture, light extraction, and phosphors. Finally, we offer a brief outlook on opportunities provided by smart LED technology.
... Blue light irradiation does not induce DNA damage (Awakowicz et al., 2009), it is absorbed by other photo-acceptors in the cell, e.g., flavins (Sadeghian et al., 2008) and cryptochromes (Bouly et al., 2007). The consequent effect is the release of nitric oxide (Opländer et al., 2013) and reactive oxygen species (Yoshida et al., 2013), which alter the cell's proliferation and differentiation rates. ...
Clinical investigations prove that blue light irradiation reduces the severity of psoriasis vulgaris. Nevertheless, the mechanisms involved in the management of this condition remain poorly defined. Despite the encouraging results of the clinical studies, no clear guidelines are specified in the literature for the irradiation scheme regime of blue light-based therapy for psoriasis. We investigated the underlying mechanism of blue light irradiation of psoriatic skin, and tested the hypothesis that regulation of proliferation is a key process. We implemented a mechanistic model of cellular epidermal dynamics to analyze whether a temporary decrease of keratinocytes hyper-proliferation can explain the outcome of phototherapy with blue light. Our results suggest that the main effect of blue light on keratinocytes impacts the proliferative cells. They show that the decrease in the keratinocytes proliferative capacity is sufficient to induce a transient decrease in the severity of psoriasis. To study the impact of the therapeutic regime on the efficacy of psoriasis treatment, we performed simulations for different combinations of the treatment parameters, i.e., length of treatment, fluence (also referred to as dose), and intensity. These simulations indicate that high efficacy is achieved by regimes with long duration and high fluence levels, regardless of the chosen intensity. Our modeling approach constitutes a framework for testing diverse hypotheses on the underlying mechanism of blue light-based phototherapy, and for designing effective strategies for the treatment of psoriasis.
... In particular, blue LEDs with wavelengths of 400-500 nm have been used for treatment in hyperbilirubinemia of infantile jaundice (Ennever, McDonagh, & Speck, 1983). Blue LEDs are reported to have phototoxic and antiproliferative effects through the generation of intracellular reactive oxygen species (ROS) (Kim et al., 2013;Yoshida et al., 2013). We previously reported that 450 nm blue LED irradiation induced apoptosis via a mitochondrial-mediated signaling pathway and reduced early stage tumor growth of melanoma cells (Oh et al., 2015). ...
The aim of this study was to determine the effects and molecular mechanism of blue light emitting diode (LED) in tumor cells. A migration and invasion assay for the metastatic behavior of mouse colon cancer CT-26 and human fibrosarcoma HT-1080 cells was performed. Cancer cell migration-related proteins were identified by obtaining a 2-dimensional gel electrophoresis (2-DE) in total cellular protein profile of blue LED-irradiated cancer cells, followed by matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) analysis of proteins. Protein levels were examined by immunoblotting. Irradiation with blue LED inhibited CT-26 and HT-1080 cell migration and invasion. The anti-metastatic effects of blue LED irradiation were associated with inhibition of matrix metalloproteinase (MMP)-2 and MMP-9 expression. P38 MAPK phosphorylation was increased in blue LED-irradiated CT-26 and HT-1080 cells, but was inhibited after pretreatment with SB203580, a specific inhibitor of p38 MAPK. Inhibition of p38 MAPK phosphorylation by SB203580 treatment increased number of migratory cancer cells in CT-26 and HT-1080 cells, indicating that blue LED irradiation inhibited cancer cell migration via phosphorylation of p38 MAPK. Additionally blue LED irradiation of mice injected with CT-26 cells expressing luciferase decreased early stage lung metastasis compared to untreated control mice. These results indicate that blue LED irradiation inhibits cancer cell migration and invasion in vitro and in vivo. This article is protected by copyright. All rights reserved.
... Previous studies have demonstrated the cytotoxic effects of blue light [35]. Blue light wavelengths (400-500 nm) commonly used in dentistry for polymerization of composite resin restorations has been proposed as a direct means of affecting local bacterial infections [4,10,36]. ...
Background:
The use of blue light has been proposed as a direct means of affecting local bacterial infections, however the use of blue light without a photosensitizer to prevent the biofilm development has not yet been explored. The aim of this study was to determine how the twice-daily treatment with blue light affects the development and composition of a matrix-rich biofilm.
Methodology/principal findings:
Biofilms of Streptococcus mutans UA159 were formed on saliva-coated hydroxyapatite discs for 5 days. The biofilms were exposed twice-daily to non-coherent blue light (LumaCare; 420 nm) without a photosensitizer. The distance between the light and the sample was 1.0 cm; energy density of 72 J cm-2; and exposure time of 12 min 56 s. Positive and negative controls were twice-daily 0.12% chlorhexidine (CHX) and 0.89% NaCl, respectively. Biofilms were analyzed for bacterial viability, dry-weight, and extra (EPS-insoluble and soluble) and intracellular (IPS) polysaccharides. Variable pressure scanning electron microscopy and confocal scanning laser microscopy were used to check biofilm morphology and bacterial viability, respectively. When biofilms were exposed to twice-daily blue light, EPS-insoluble was reduced significantly more than in either control group (CHX and 0.89% NaCl). Bacterial viability and dry weight were also reduced relative to the negative control (0.89% NaCl) when the biofilms were treated with twice-daily blue light. Different morphology was also visible when the biofilms were treated with blue light.
Conclusions:
Twice-daily treatment with blue light without a photosensitizer is a promising mechanism for the inhibition of matrix-rich biofilm development.
Background
Phototherapies based on sunlight, infrared, ultraviolet, visible, and laser-based treatments present advantages like high curative effects, small invasion, and negligible adverse reactions in cancer treatment. We aimed to explore the potential therapeutic effects of blue light emitting diode (LED) in human hepatoma cells and decipher the underlying cellular and molecular mechanisms.
Methods
Wound healing and transwell assays were employed to probe the inhibition of the invasion and migration of hepatocellular carcinoma cells in the presence of blue LED. The sphere-forming test was used to evaluate the effect of LED blue light irradiation on cancer stem cell properties. Immunofluorescence and western blotting were used to detect the changes in γ-H2AX. The Cell Counting Kit-8 assay, 5-ethynyl-2′-deoxyuridine staining, and colony formation assay were used to detect the combined effect of blue LED and sorafenib on cell proliferation inhibition.
Results
We demonstrated that the irradiation of blue LED light in hepatoma cells could lead to cell proliferation reduction along with the increase of cell apoptosis. Simultaneously, blue LED irradiation also markedly suppressed the migration and invasion ability of human hepatoma cells. Sphere formation analysis further revealed the decreased cancer stemness of hepatoma cells upon blue LED irradiation. Mechanistically, blue LED irradiation significantly promoted the expression of the phosphorylation of the core histone protein H2AX (γ-H2AX), a sensitive molecular marker of DNA damage. In addition, we found that the combined treatment of blue LED irradiation and sorafenib increased cancer cell sensitivity to sorafenib.
Conclusion
Collectively, we demonstrated that blue LED irradiation exhibited anti-tumor effects on liver cancer cells by inducing DNA damage and could enhance chemosensitivity of cancer cells, which represents a potential approach for human hepatoma treatment.
This article focuses on the current understanding and concerns over the blue-light hazard when using dental light-curing units. It also provides information and safety protocols to guide the practitioner in making important decisions regarding dental personnel's health and the quality of dental restorations.
Acute lung injury (ALI) impaired the function of blood oxygen exchange function, resulting in tissue hypoxia and patient death. Recently, human umbilical cord mesenchymal stem cells (hUCMSCs) are thought to mitigate the effects of ALI, which boosts researchers' interest in employing stem cell-based therapies to manage ALI. However, as a novel therapy, hUCMSCs still face various limitations such as migrating weakly and insufficient proliferation in vivo. Photobiomodulation (PBM) effciently promotes cell proliferation, migration and homing, which presents a promising strategy for overcoming above limitations. In this study, PBM was emerged to intervene hUCMSCs through detecting cell proliferation, oxidative stress-related factors and inflammatory factors. These results assuredly confirmed that PBM enhanced the antioxidant capacity of cells and improved cell survival in vitro experiments. In vivo, PBM-intervened hUCMSCs intuitively reduce thickness of alveolar septum, excessive secretion of inflammatory factors, relieves bleeding, edema and fibrosis. As a physical intervention, PBM further strengthens the therapeutic effect of hUCMSCs and depicted a hopeful therapy in ALI treatment.
Objectives:
Antimicrobial photodynamic therapy (aPDT) in periodontal pockets using lasers is difficult to perform in some cases because of the high cost of irradiation equipment and the narrow irradiation field. The purpose of the present study was to examine the effects of aPDT in combination with a plaque-disclosing solution and blue light-emitting diode (LED), which are used for composite resin polymerization.
Methods:
The reactive oxygen species generated by irradiating 0.001% RB or MB with blue light were analyzed using electron spin resonance spectroscopy. Blue-light exposure was performed at 6.92, 20.76 and 124.6 J. The microorganism to be sterilized was Porphyromonas gingivalis. After aPDT, colony-forming units (CFU) were measured to estimate cell survival. Carbonylated protein (PC) levels were used to evaluate oxidative stress. All statistical analyses were performed with Tukey's multiple comparisons test or the unpaired t-test.
Results:
Singlet oxygen (1O2) generation was confirmed by RB+blue LED. 1O2 production was significantly greater with the blue LED irradiation of RB than that of MB (p<0.0001). CFU were significantly lower in the blue LED-irradiated group than in the non-LED-irradiated group (p < 0.01). The bactericidal effect increased in a time-dependent manner. aPDT increased PC levels. No morphological changes were observed in P. gingivalis.
Conclusions:
The present results suggest that aPDT exerts bactericidal effects against P. gingivalis by increasing oxidative stress through the generation of 1O2 in cells. Periodontal disease may be treated by aPDT using the equipment available in dental offices.
Mercury vapor lamps, widely used in the majority of ultraviolet (UV) disinfection systems, have many disadvantages: large size, low resistance to shock, and high energy consumption. The advantage of light emitting diode (LED) lamps is to be compact light sources and to produce UV light at a single wavelength, which allows UV disinfection systems with optimized numbers and wavelength LEDs as a function of microorganisms to be inactivated to be designed. UV light is able to age the package materials and induces yellowing, carbonization, and nebulization. Infrared (IR) optoelectronic technology is an important branch of modern optoelectronic technology, and its development affects all fields of human life and social development. IR imaging technology is widely used in many areas, including charge coupled devices, image positioning systems, and night vision equipment. LED therapy is becoming increasingly important in several health treatment areas, such as biomedical engineering, deontology, physical therapy, and dermatology.
WLEDs have lately been the preferred lighting device based on properties such as energy saving, high efficiency, longevity, and environmental protection. However, studies on the safety of white light-emitting diode (WLED) are limited. In our previous study, we found that WLED light (4000 K ± 500 K color temperature, 250 lx, and 20 min exposure) is photocytotoxic to three mammalian cell lines by causing cell lipid peroxidation. To further investigate the potential photocytotoxicity of WLEDs on the human body, we used two human eye cell lines SRA01/04 and D407 as target cells for evaluating its potential phototoxicity on the human eye in the present study based on cell viability, apoptosis, and intracellular oxidative stress assays, as well as the activation levels of reactive oxygen species (ROS)-related apoptosis pathways, including extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK) and p38 kinase (p38), using mitogen-activated protein kinase (MAPK) signaling pathway assays. The results showed that WLED light has photocytotoxicities on SRA01/04 and D407 cells, which were both in a time-, irradiance-, and color temperature-dependent manner and strongest at the conditions of 2 h irradiation time, 60 W/m² irradiance, and 4000 K color temperature. Moreover, the photocytotoxicity of red light-emitting diode (LED) light was the strongest in the three tested monochromatic light compositions of WLED. Mechanism studies show that the potential phototoxicity of WLED on human lens epithelium and retinal pigment epithelium may be caused by its induced oxidative stress damage via the JNK and p38 MAPKs pathways.
Background and objectives:
Hospital-acquired infections (HAIs) and multidrug resistant bacteria pose a significant threat to the U.S. healthcare system. With a dearth of new antibiotic approvals, novel antimicrobial strategies are required to help solve this problem. Violet-blue visible light (400-470 nm) has been shown to elicit strong antimicrobial effects toward many pathogens, including representatives of the ESKAPE bacterial pathogens, which have a high propensity to cause HAIs. However, phototherapeutic solutions to prevention or treating infections are currently limited by efficient and nonobtrusive light-delivery mechanisms.
Study design/materials and methods:
Here, we investigate the in vitro antimicrobial properties of flexible Corning® light-diffusing fiber (LDF) toward members of the ESKAPE pathogens in a variety of growth states and in the context of biological materials. Bacteria were grown on agar surfaces, in liquid culture and on abiotic surfaces. We also explored the effects of 405 nm light within the presence of lung surfactant, human serum, and on eukaryotic cells. Pathogens tested include Enterococcus spp, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp., Staphylococcus epidermidis, Streptococcus pyogenes, Candida albicans, and Escherichia coli.
Results:
Overall, the LDF delivery of 405 nm violet-blue light exerted a significant degree of microbicidal activity against a wide range of pathogens under diverse experimental conditions.
Conclusions:
The results exemplify the fiber's promise as a non-traditional approach for the prevention and/or therapeutic intervention of HAIs. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.
As a new light source, light emitting diode (LED) with high brightness and lower cost has been rapidly developed in medical application and light therapy. LED phototherapy can activate target cells with appropriate power and adequate energy density. This review provides general information on therapeutic applications of blue, green, yellow, red, and infrared LED in medical treatments for various physical abnormalities and on bio-imaging. The bio-imaging system is improved by decreasing the number of microscopes apparatuses including neutral-density filter, excitation filters and mechanical shutters. The numbers of excitation photons are increased and the fluorescent excitation efficiency is improved at cellular level. In the target tissue, the therapeutic effect of LEDs is dependent on incident photons irrespective of the system used to generate these photons. Photomodulated light from LED device is delivered in pulsed mode with specific pulse sequences and time. Too low or too high dose of energy may be ineffective at all. Clinical applications of LED light depending on different wavelengths are summarized. The author's photo-oncomic experiments using a specific blue light emitting diode were introduced, showing that blue LED possessed anti-proliferative and anti-metastatic abilities in cancer cells and mice. As a promising light source, photo-oncomic approach of blue LED could be applied to treat cancers and inflammatory diseases.
LED technology has the extraordinary ability to reduce energy consumption, constituting an economic and ecological advantage, so it is planned to replace incandescent, halogen and other inefficient bulbs for public and domestic lighting with LEDs. LEDs present specific spectral and energetic characteristics compared with those of other domestic light sources, so the potential risks for human health of these bulbs need to be explored.
The aim of this study was to assess cytotoxicity and genotoxicity of light emitted by different commercial light bulbs: incandescent, halogen, and two LED bulbs with different correlated color temperatures. The evaluation was done on ARPE-19 as a specific cell model for eye toxicity and on BEAS-2B as a good cell model for toxicology tests.
Light induced mainly cytotoxic effects on ARPE-19 and DNA damage on BEAS-2B, so different cell lines showed different biological responses. Moreover, our findings indicate that among the four bulbs, cold LED caused the highest cytotoxic effect on ARPE-19 and the highest genotoxic and oxidative effect on BEAS-2B. Cold LED is probably able to cause more cellular damage because it contains more high-energy radiations (blue). These results suggest that LED technology could be a safe alternative to older technologies, but the use of warm LED should be preferred to cold LED, which can potentially cause adverse effects on retinal cells.
The present study was performed to examine the induction of apoptotic cell death and autophagy by blue LED irradiation, and the contribution of autophagy to apoptosis in B cell lymphoma A20 and RAMOS cells exposed to blue LED. Irradiation with blue LED reduced cell viability and induced apoptotic cell death, as indicated by exposure of phosphatidylserine on the plasma outside membrane and fragmentation of DNA. Furthermore, the mitochondrial membrane potential increased, and apoptotic proteins (PARP, caspase 3, Bax, and bcl-2) were observed. In addition, the level of intracellular superoxide anion (O2(•-)) gradually increased. Interestingly the formation of autophagosomes and level of LC3-II were increased in blue LED-irradiated A20 and RAMOS cells, but inhibited after pretreatment with 3-methyladenine (3-MA), widely used as an autophagy inhibitor. Inhibition of the autophagic process by pretreatment with 3-MA blocked blue LED irradiation-induced caspase-3 activation. Moreover, a significant reduction of both the early and late phases of apoptosis after transfection with ATG5 and beclin 1 siRNAs was shown by the annexin V/PI staining, indicating a crucial role of autophagy in blue LED-induced apoptosis in cells. Additionally, the survival rate of mice irradiated with blue LED after injection with A20 cells increased compared to the control group. Our data demonstrate that blue LED irradiation induces apoptosis via the mitochondrial-mediated pathway, in conjunction with autophagy. Further studies are needed to elucidate the precise mechanism of blue LED-induced immune cell death.
Violet-blue light is toxic to mammalian cells, and this toxicity has been linked with cellular production of H2O2. In this report, we show that violet-blue light, as well as UVA, stimulated H2O2 production in cultured mouse, monkey, and human cells. We found that H2O2 originated in peroxisomes and mitochondria, and it was enhanced in cells overexpressing flavin-containing oxidases. These results support the hypothesis that photoreduction of flavoproteins underlies light-induced production of H2O2 in cells. Because H2O2 and its metabolite, hydroxyl radicals, can cause cellular damage, these reactive oxygen species may contribute to pathologies associated with exposure to UVA, violet, and blue light. They may also contribute to phototoxicity often encountered during light microscopy. Because multiphoton excitation imaging with 1,047-nm wavelength prevented light-induced H2O2 production in cells, possibly by minimizing photoreduction of flavoproteins, this technique may be useful for decreasing phototoxicity during fluorescence microscopy.
Light-curing units used for polymerizing restorative resins produce heat during operation. Newer curing units with concentrating light guides or different light sources may require shorter curing times, however, the effect of such modifications on temperature transfer to the pulp is unknown. This study examined the effect of high output light-curing units on temperature transfer through resin composite and dentin. Temperature rise was measured for 40 seconds for one curing light (Optilux 401 Curing Light) with either a standard 8 mm light guide tip or a light-concentrating tip (Turbo Light Guide), and for three seconds with a plasma arc lamp (Apollo 95E Curing Light). Temperatures were directly recorded at the tip of the light guide and through a sandwich composed of a 1 mm thick pre-cured cylinder of resin composite and dentin (dentin thickness either 0.58 mm or 1.45 mm). The mean temperature rise ranged from 1.8degrees C, measured through the sandwich of 1 mm of composite and 1.45 mm of dentin with the plasma are unit, to 26.4degrees C measured directly on the Turbo light guide. For each light guide, the temperature increase was greatest when measured directly on the curing tip and least when measured through the composite and 1.45 mm dentin specimens. When measured through the composite/dentin sandwich, the plasma arc unit produced the lowest temperature increase (0.58 mm thick dentin specimen = 5.1 degrees C; 1.45 mm thick dentin specimen = 1.8 degrees C). For a given thickness of resin, the differences in temperature change for all comparisons among the three curing unit/light guides were significant at the 95% level of confidence. Also, for a given light, the differences in temperature for all comparisons among the dentin thicknesses were significant at the 95% level of confidence. However, there were three comparisons of light unit and dentin thickness interaction that were not significant at the 95% leyel of confidence. For all other comparisons of interaction, significant differences were found at the 95% level of confidence. The temperature increased by 42% to 56% when the Turbo Light Guide was used compared to the standard light guide for thick and thin dentin specimens, respectively.
Previous studies have reported that blue light (400-500 nm) inhibits cell mitochondrial activity. We investigated the hypothesis that cells with high energy consumption are most susceptible to blue-light-induced mitochondrial inhibition. We estimated cell energy consumption by population doubling time, and cell survival and growth by succinate dehydrogenase (SDH) activity. Six cell types were exposed to 5 or 60 J/cm(2) of blue light from quartz-tungsten-halogen (QTH), plasma-arc (PAC), or argon laser sources in monolayer culture. Post-light SDH activity correlated positively with population doubling time (R(2) = 0.91 for PAC, 0.76 for QTH, 0.68 for laser); SDH activity increased for cell types with the longest doubling times and was suppressed for cell types with shorter doubling times. Thus, light-induced exposure differentially affects SDH activity, cell survival, and growth, depending on cell energy consumption. Blue light may be useful as a therapeutic modulator of cell growth and survival.
Exposure of biological chromophores to ultraviolet radiation can lead to photochemical damage. However, the role of visible light, particularly in the blue region of the spectrum, has been largely ignored. To test the hypothesis that blue light is toxic to non-pigmented epithelial cells, confluent cultures of human primary retinal epithelial cells were exposed to visible light (390-550 nm at 2.8 milliwatts/cm2) for up to 6 h. A small loss of mitochondrial respiratory activity was observed at 6 h compared with dark-maintained cells, and this loss became greater with increasing time. To investigate the mechanism of cell loss, the damage to mitochondrial and nuclear genes was assessed using the quantitative PCR. Light exposure significantly damaged mitochondrial DNA at 3 h (0.7 lesion/10 kb DNA) compared with dark-maintained controls. However, by 6 h of light exposure, the number of lesions was decreased in the surviving cells, indicating DNA repair. Isolated mitochondria exposed to light generated singlet oxygen, superoxide anion, and the hydroxyl radical. Antioxidants confirmed the superoxide anion to be the primary species responsible for the mitochondrial DNA lesions. The effect of lipofuscin, a photoinducible intracellular generator of reactive oxygen intermediates, was investigated for comparison. Exposure of lipofuscin-containing cells to visible light caused an increase in both mitochondrial and nuclear DNA lesions compared with non-pigmented cells. We conclude that visible light can cause cell dysfunction through the action of reactive oxygen species on DNA and that this may contribute to cellular aging, age-related pathologies, and tumorigenesis.
Light emitting diodes (LEDs) are devices that are used in a myriad of
applications, such as indicator lights in instruments, signage,
illuminations, and communication. This graduate textbook covers all
aspects of the technology and physics of infrared, visible-spectrum, and
white light-emitting diodes (LEDs) made from III-V semiconductors. It
reviews elementary properties of LEDs such as the electrical and optical
characteristics. Exercises and illustrative examples reinforce the
topics discussed.
Objectives
The aim of the present study was to test the hypothesis that the use of a light curing unit (LCU) with high light power would result in a higher temperature and therefore a statistically significant lower number of living human gingiva fibroblasts within a pulp chamber model than the use of a light emitting diode (LED) LCU.
Materials and methods
The composites Admira, Grandio, Filtek Supreme and Filtek Z250 were polymerized with the LCUs Swiss Master Light, Optilux 501 and an LED LCU prototype in a mould on top of a pulp chamber model. The temperature was recorded within the pulp chamber with a thermocouple. The cytotoxicity of the polymerized samples was tested by using the MTT test.
Results
In general there was no considerable difference in the temperature increase within the pulp chamber model for the different LCUs and composites. There was no statistically significant difference in the cell number (P=0.3767) when the different LCUs were used.
Conclusion
Using a high power halogen LCU for a short time or a standard halogen or LED LCU for a longer time did not result in a considerable difference in the temperature increase or the number of living cells within a pulp chamber model. This study indicates not only that the temperature may have an effect on the living cells, but also that cells may be negatively affected by the unpolymerized composite or light of the LCUs.—Reprinted with permission of Elsevier Publishing.
The advent of high luminance AlInGaP and InGaN LED technologies has prompted the use of LED devices in new applications formally illuminated by incandescent lamps. The luminous efficiencies of these new LED technologies equals or exceeds that attainable with incandescent sources, with reliability factors that far exceed those of incandescent sources. The need for a highly efficient, dependable, and cost effective replacement for incandescent lamps is being fulfilled with high luminance LED lamps. This paper briefly described some of the new applications incorporating high luminance LED lamps, traffic signals and roadway signs for traffic management, automotive exterior lighting, active matrix and full color displays for commercial advertising, and commercial aircraft panel lighting and military aircraft NVG compatible lighting.
Objectives:
The majority of modern resin-based oral restorative biomaterials are cured via photopolymerization processes. A variety of light sources are available for this light curing of dental materials, such as composites or fissure sealants. Quartz-tungsten-halogen (QTH) light curing units (LCUs) have dominated light curing of dental materials for decades and are now almost entirely replaced by modern light emitting diode light curing units (LED LCUs). Exactly 50 years ago, visible LEDs were invented. Nevertheless, it was not before the 1990s that LEDs were seriously considered by scientists or manufactures of commercial LCUs as light sources to photopolymerize dental composites and other dental materials. The objective of this review paper is to give an overview of the scientific development and state-of-the-art of LED photopolymerization of oral biomaterials.
Methods:
The materials science of LED LCU devices and dental materials photopolymerized with LED LCU, as well as advantages and limits of LED photopolymerization of oral biomaterials, are discussed. This is mainly based on a review of the most frequently cited scientific papers in international peer reviewed journals. The developments of commercial LED LCUs as well as aspects of their clinical use are considered in this review.
Results:
The development of LED LCUs has progressed in steps and was made possible by (i) the invention of visible light emitting diodes 50 years ago; (ii) the introduction of high brightness blue light emitting GaN LEDs in 1994; and (iii) the creation of the first blue LED LCUs for the photopolymerization of oral biomaterials. The proof of concept of LED LCUs had to be demonstrated by the satisfactory performance of resin based restorative dental materials photopolymerized by these devices, before LED photopolymerization was generally accepted. Hallmarks of LED LCUs include a unique light emission spectrum, high curing efficiency, long life, low energy consumption and compact device form factor.
Significance:
By understanding the physical principles of LEDs, the development of LED LCUs, their strengths and limitations and the specific benefits of LED photopolymerization will be better appreciated.
Efficient blue electroluminescence, peaked at 436 nm, is demonstrated from polymer light-emitting diodes operating at high brightness. A dioctyl-substituted polyfluorene was used as the emissive layer in combination with a polymeric triphenyldiamine hole transport layer. The luminance reaches 600 cd/m2 at a current density of 150 mA/cm2 for a bias voltage of 20 V, corresponding to an efficiency of 0.25 cd/A and a luminosity of 0.04 lm/W. These values are optimized at a critical emissive layer thickness. © 1998 American Institute of Physics.
Several mechanisms have been proposed to explain the vascular toxicity of arsenic. Some of them are described in this work,
such as stress-induced premature senescence (SIPS), dedifferentiation, and medial vascular calcification, and they all affect
vascular smooth muscle cells (VSMC). Rat aortic VSMC were treated with 1–100µM of either sodium arsenate (AsV), sodium arsenite (AsIII), monomethylarsonic acid, or dimethylarsinic acid. None of the treatments induced VSMC calcification in the presence of 1mM
inorganic phosphate (Pi), but 1µM AsIII did increase calcification when induced with 2.5mM Pi. A lactate dehydrogenase assay revealed that this increase was explained
by a rise in cytotoxicity due to simultaneous incubation with 1µM AsIII and 2.5mM Pi. This calcification increase was also observed in the aortas of a vascular calcification model: 5/6 nephrectomized
rats fed with a high Pi diet and treated with vitamin D3. Several known mechanisms that might explain arsenic toxicity in our experimental model were discarded: apoptosis, oxidative
stress, and inflammasome activation. Nevertheless, both senescence-associated β-galactosidase activity and p21 expression
were increased by AsIII, which reveals the induction of SIPS. AsIII also caused dedifferentiation of VSMC, as shown by the reduced expression of the VSMC markers SM22α and calponin. Senescence
and gene expression were also observed in the aortas of healthy rats treated with 50 ppm AsV in drinking water for 1 month. In conclusion, both premature senescence in aortic VSMC with phenotypic dedifferentiation
and the increase of Pi-induced calcification are novel mechanisms of arsenic vasculotoxicity.
Dental resin curing blue light has been used in the treatment of tooth bleaching and to restore teeth with resin-based composite fillings. However, there has been little consideration of its effect on oral tissues such as dental pulp and oral mucosa. The aim of this study was to investigate whether dental resin curing blue light irradiation affects the dental pulp, especially the blood vessels that are known as the first target of reactive oxygen species (ROS), which play an important role in vascular reactivity. We found that blue light irradiation increased the level of lipid peroxidation in isolated rat aorta blood vessels by measuring malondialdehyde. Furthermore, cell proliferative activity was decreased in a time-dependent manner and apoptosis of human aorta vascular smooth muscle cells (VSMCs) was induced. These results indicated that (ROS) such as hydrogen peroxide and hydroxyl radicals were generated in VSMCs by irradiation with blue light, and they induced cytotoxicity associated with oxidative stress, which increased lipid peroxidation and apoptosis. In addition, N-acetyl-l-cysteine, which is a typical intracellular antioxidant, protected VSMCs against cytotoxicity associated with oxidative stress. These findings suggested that antioxidants may be used to prevent oxidative stress in dental pulp by repeated and/or multiple treatments with blue light irradiation in future dental treatments.
Experimental light-cured composite resins were exposed to a narrow-band light at a constant quantum number using a narrow-band interference filter. The IR spectra of the cured resin specimens were measured before and after extraction of residual monomers. Degree of conversion (DC) and polymerization conversion (PC) were calculated from these IR spectra. The light in 410-550 nm could be polymerized. With a brief exposure (5 s), DC and PC were affected by the wavelength. The effect of wavelength between 410 and 490 nm decreased with increasing duration of exposure. The most efficient wavelength was 470 nm and the most adequate wavelength was in the 450-490 nm wavelength range. The absorbance of camphorquinone strongly affected polymerization, especially during the initial stage. However, from the relationship between DC or PC and exposure energy, polymerization depended not only on the wavelength of the light, but also on the exposure energy.
With ever increasing interest in cosmetic enhancement of dentition by dentists and patients alike, this article introduces a new light-activated bleaching system that adds up to total patient satisfaction and reduced chair time. The chairside application of hydrogen peroxide 30% was effective in lightening a moderate case of tetracycline staining. The uniqueness of this system allows the practitioner complete control within an office setting, and it provides the patient with an immediate result. The ease of application and strict supervision of a dentist has allowed this system to satisfy recent watchdogs of the Federal Drug Administration.
The ability of hydroxyl radical (.OH) scavengers to reduce DNA breakage in isolated DNA from Bacillus subtilis by either gamma radiation or monochromatic radiation in the UVA region (365 nm) was examined by comparing dose reduction factors (the ratio of dose required to induce n DNA breaks in the absence to the presence of quencher). Previous data have demonstrated that acetate, formate, azide, and mannitol protect supercoiled DNA against gamma-radiation-induced ssb (single-strand breaks-relaxation of supercoil by first nick) in close agreement with the rate at which their solutions quench .OH. Here we show that these quenchers also protect against 365-nm-induced ssb. The ratios for protection against 365-nm induced DNA ssb in isolated B. subtilis DNA by the four quenchers are also in proportion to their ability to quench .OH. In view of the diverse chemical nature of the quenchers and the wide range of concentrations involved, these findings are evidence that both these radiations may induce ssb in DNA via a common step that might involve .OH.
Rats have been extensively used in light damage studies. Retinal damage threshold for white light were found at 1-10 J/cm2, and the action spectrum resembled the absorption spectrum of visual pigment. We wished to answer the question whether a different class of light damage, the "blue light hazard", with white light damage thresholds at about 300 J/cm2, and an action spectrum peaking in the ultra-violet, could also be demonstrated in rat. To that purpose 5 deg patches of retina were exposed to white xenon light with exposure times between 10 sec and 1 hr. We found that for funduscopic threshold damage the product of irradiance and exposure time was constant at a level of 315 J/cm2. Thereafter, the action spectrum was measured by exposing rat eyes to narrow band spectral lights. Threshold irradiant dose ranged from 4 J/cm2 at 379 nm to 2000 J/cm2 at 559 nm. Thus, susceptibility for damage sharply increased towards the ultra-violet, just like in earlier monkey studies. We conclude that in similar experimental conditions susceptibility to photic injury in rat is comparable to that in primates. Rat is the first species for which two different action spectra of photochemical damage have been established.
Several endogenous cellular constituents were tested for their ability to produce superoxide anion (O2-) from ground-state molecular oxygen upon irradiation by solar radiation. The pyridine cofactors NADPH and NADH, riboflavin, and the nucleosides 2-thiouracil and 4-thiouridine were found to sensitize the transmission of photon energy from solar radiation and monochromatic radiation (290, 334, 365, and 405 nm) to oxygen, resulting in O2- formation, as detected by superoxide dismutase-inhibitable cytochrome c reduction. Quantum yields for the production of O2- indicate that NADPH is the most efficient and riboflavin the least efficient of the compounds tested. These data indicate that endogenous compounds may participate in the production of O2- by solar radiation and imply that O2- may play a role in sunlight-induced erythema and dermal carcinogenesis.
Chain breaking antioxidants scavenge the chain carrying oxygen radicals and suppress the peroxidation of liposomal and biological membranes in aqueous dispersions. Vitamin E scavenges peroxyl radicals rapidly and its lateral diffusion is suggested to be fast, but its antioxidant efficiency in the liposomal and bio-membranes appears to be considerably smaller than in homogeneous solution. Water soluble chain breaking antioxidants, such as uric acid, cysteine, glutathione, and vitamin C, scavenge radicals in the aqueous region and suppress the peroxidation. However, they cannot scavenge the peroxyl radicals within the lipid region of the membranes. Nevertheless, vitamin C can interact with vitamin E radical, probably at membrane-water interface, and regenerate vitamin E.
To use the technique of infrared thermography for non-invasive monitoring of temperature changes during polymerization of resin composite by measuring the infra-red emission from the surfaces of resin composite restorations during photocuring.
In this study 10 patient volunteers had resin composite restorations placed in upper incisor teeth and during photocuring the temperature rise within the composite was measured using the Thermovision 900 infra-red scanning system.
The results demonstrate that the exotherm is almost instantaneous, occurring as soon as the light source is activated and rising to a peak at approximately 30 s before levelling off. The measurements suggest that a maximum temperature increase of 12 degrees C could occur, although this may only be for a short period (< 15 s).
The range of temperature rise measured in this study (mean 5.4 degree C +/- 2.5 degree C) would suggest that the pulp may be endangered by the temperature rise which occurs during resin composite polymerization in vivo.
Success in using light-cured resin composites relies heavily on proper curing time and intensity. Because these factors are so critical, the authors reviewed the literature to arrive at guidelines for optimal curing conditions. The guidelines emphasize maintenance of the curing lights, consideration of the type of restorative material used and duration of exposure.
Free radicals, such as superoxide, hydroxyl and nitric oxide, and other reactive oxygen species (ROS), such as hydrogen peroxide, are formed in vivo. Imbalance between production of ROS and anti-oxidant defence can result in oxidative stress, which may arise either from deficiencies of anti-oxidants (such as glutathione, ascorbate or alpha-tocopherol) and/or from increased formation of ROS. Oxidative stress can result in glutathione depletion, lipid peroxidation, membrane damage and DNA strand breaks as well as activation of proteases, nucleases and protein kinases. Some degree of oxidative stress occurs in most, if not all, human diseases, and the major question to be answered is whether it makes a significant contribution to the disease pathology. In the case of atherosclerosis, evidence from studies with the chain-breaking anti-oxidant probucol and from epidemiological work suggests that oxidative damage does indeed make an important contribution to plaque development.
Accumulation of lipofuscin (LF) is a prominent feature of aging in the human retinal pigment epithelium (RPE) cells. This age pigment exhibits substantial photoreactivity, which may increase the risk of retinal photodamage and contribute to age-related maculopathy. In a previous study, we detected singlet oxygen generation by lipofuscin granules excited with blue light. In this paper we investigated the ability of hydrophobic components of lipofuscin to photogenerate singlet oxygen in non-polar environments. Singlet oxygen was detected directly by monitoring its characteristic phosphorescence at ca 1270 nm. The action spectrum of singlet oxygen formation indicated that this process was strongly wavelength-dependent and its efficiency decreased with increasing wavelength by a factor of ten, comparing 420 nm and 520 nm. The quantum yield of singlet oxygen increased with increasing concentration of oxygen. Using laser flash photolysis we studied the possible mechanism of singlet oxygen formation. The observed transient, with a broad absorption spectrum peaking at around 440 nm, was identified as a triplet with lifetime ca 11 microseconds. It was quenched by both molecular oxygen and beta-carotene with concomitant formation of a beta-carotene triplet state. These results indicate the potential role of hydrophobic components of lipofuscin in blue light-induced damage to the RPE.
We have investigated the autofluorescence of viable mammalian cells (DU-145 and V79) with a confocal laser scanning microscope equipped with a UV laser. Our aim was to investigate the autofluorescence dependence on different treatments in mitochondria and lysosomes by using different reagents and to improve the confocal laser scanning microscope image quality by deconvolution. The following conclusions were drawn from the results: (1) not all of the autofluorescence comes from mitochondria; (2) one can significantly affect the signal which comes from the mitochondria; (3) the other organelles involved are probably lysosomes; (4) it is harder to affect the autofluorescence signal from the lysosomes than that from the mitochondria, and (5) deconvoluted autofluorescence images provide better information than undeconvoluted ones.
The purpose of this in vitro study was to measure the pulp chamber temperature increase induced during composite resin polymerization with various visible light-curing units.
A Class II cavity was prepared in an extracted molar tooth, leaving a dentin layer 1 mm thick between pulp chamber and proximal cavity wall. A 2 mm composite resin layer was applied to the proximal box and light-cured with the selected curing units: Heliolux II (H; 320 mW/cm2), QHL 75 (Q; 505 mW/cm2), Astralis 5 (A; 515 mW/cm2), Optilux 500 (O; 670 mW/cm2), Elipar Highlight (EH; 730 mW/cm2), ADT 1000 PAC (P; 1196 mW/cm2). Light-curing took place for 40 s (H, A, Q, O, EH), 5 and 10 s (P). Measurement of pulp chamber temperature changes (starting temperature: 37.0 +/- 0.1 degrees C) during polymerization was performed with a K-type thermocouple positioned at the pulp-dentin junction. Mean values were calculated from 10 measurements with each light-curing unit. ANOVA and Dunnett t-test were used for statistical analyses.
Maximum temperature changes varied significantly depending on the light-curing unit used: 2.9 +/- 0.3 degrees C (H), 4.7 +/- 0.5 degrees C (A), 5.4 +/- 0.3 degrees C (P, 5 s), 5.6 +/- 0.4 degrees C (Q), 6.1 +/- 0.2 degrees C (EH, 2-step mode: 100 mW/cm2 over 10 s, 730 mW/cm2 over 30 s), 6.9 +/- 0.4 degrees C (EH), 7.3 +/- 0.3 degrees C (O), 7.8 +/- 0.9 degrees C (P, 10 s).
It is concluded that light-polymerization with curing units characterized by high energy output (A,EH,O,P,Q) causes significantly higher pulp chamber temperature changes as compared to the conventional curing light (H). Therefore, clinicians should be aware of the potential thermal hazard to the pulp which might result from visible-light curing of composite resins.
Age-related macular degeneration (AMD) is the leading cause of blind registration in the developed world, and yet its pathogenesis remains poorly understood. Oxidative stress, which refers to cellular damage caused by reactive oxygen intermediates (ROI), has been implicated in many disease processes, especially age-related disorders. ROIs include free radicals, hydrogen peroxide, and singlet oxygen, and they are often the byproducts of oxygen metabolism. The retina is particularly susceptible to oxidative stress because of its high consumption of oxygen, its high proportion of polyunsaturated fatty acids, and its exposure to visible light. In vitro studies have consistently shown that photochemical retinal injury is attributable to oxidative stress and that the antioxidant vitamins A, C, and E protect against this type of injury. Furthermore, there is strong evidence suggesting that lipofuscin is derived, at least in part, from oxidatively damaged photoreceptor outer segments and that it is itself a photoreactive substance. However, the relationships between dietary and serum levels of the antioxidant vitamins and age-related macular disease are less clear, although a protective effect of high plasma concentrations of alpha-tocopherol has been convincingly demonstrated. Macular pigment is also believed to limit retinal oxidative damage by absorbing incoming blue light and/or quenching ROIs. Many putative risk-factors for AMD have been linked to a lack of macular pigment, including female gender, lens density, tobacco use, light iris color, and reduced visual sensitivity. Moreover, the Eye Disease Case-Control Study found that high plasma levels of lutein and zeaxanthin were associated with reduced risk of neovascular AMD. The concept that AMD can be attributed to cumulative oxidative stress is enticing, but remains unproven. With a view to reducing oxidative damage, the effect of nutritional antioxidant supplements on the onset and natural course of age-related macular disease is currently being evaluated.
Objectives:
This study assessed the effects of three common dental photo-curing light sources (quartz-tungsten-halogen (QTH), plasma-arc (PAC), and laser) on the cellular function of fibroblasts in vitro.
Methods:
Mouse fibroblasts were exposed to light from dental photo-curing units for clinically relevant durations, with total energy exposures ranging from 1.3 to 60 J/cm(2). The temperature rise of the cell-culture medium was measured to assess any possible effect from temperature increases, and cellular function was assessed by succinic dehydrogenase (SDH) activity of mitochondria. To directly compare the three light sources, additional experiments were done using equivalent total energy exposures from each source by adjusting the exposure durations for each unit.
Results:
In experiments that used clinically relevant exposure durations for each light, exposures ranging from 5 J/cm(2) (laser) to 15 J/cm(2) (PAC, QTH) irreversibly suppressed SDH activity nearly 100% when compared to no-light controls up to 72 h post-exposure. For the PAC and QTH sources, exposures as low as 3.5 J/cm(2) also irreversibly suppressed SDH activity. When equivalent energies were used from each light source, exposures of 1 J/cm(2) did not suppress SDH activity for the QTH and laser sources, but significantly (50%) suppressed SDH for the PAC source, indicating a difference in the biological effects of the outputs of the different curing units. Equivalent energy exposure experiments also indicated a definite dependence of SDH activity on the total light energy of exposure. Temperature rises ranged from 2 to 9 degrees C, and elevated temperatures lasted for 60-300 s above the base temperature of 37 degrees C, but peak temperature and the duration of temperature elevation were not always related and depended on the light source used.
Significance:
Results from the current study indicate that these photo-curing sources pose some risk of disrupting cellular function in vivo. Further study is necessary in other cell types and under more clinically relevant conditions to estimate the in vivo risk of photo-curing to oral tissues.
The mechanisms of bleaching of discolored coronal teeth using hydrogen peroxide (H2O2) were investigated. In a scanning-electron-microscopy study, the intertubular dentin and peritubular dentin were dissolved by high concentrations of H2O2, which is used for bleaching. The X-ray diffraction study showed that hydroxyapatite was not influenced by H2O2. In an electron-spin-resonance study, more hydroxyl radical (* OH) was detected as the H2O2 concentration was increased. When amino acids that are core components of dentin proteins, such as proline and alanine, were added to H2O2, the generation of * OH decreased, but there was no change when glycine was added. A nuclear-magnetic-resonance study showed that proline was degraded completely by H2O2, the structure of alanine changed slightly, and glycine was not affected by H2O2. It is suggested that H2O2 and * OH do not influence the inorganic tissue of dentin but attack the organic component of dentin. These facts suggest that * OH has the main role in tooth bleaching with H2O2.
Throughout the lifetime of an individual, light is focused onto the retina. The resulting photooxidative stress can cause acute or chronic retinal damage. The pathogenesis of age-related macular degeneration (AMD), the leading cause of legal blindness in the developed world, involves oxidative stress and death of the retinal pigment epithelium (RPE) followed by death of the overlying photoreceptors. Evidence suggests that damage due to exposure to light plays a role in AMD and other age-related eye diseases. In this work a system for light-induced damage and death of the RPE, based on the human ARPE-19 cell line, was used. Induction of mitochondria-derived reactive oxygen species (ROS) is shown to play a critical role in the death of cells exposed to short-wavelength blue light (425 +/- 20 nm). ROS and cell death are blocked either by inhibiting the mitochondrial electron transport chain or by mitochondria-specific antioxidants. These results show that mitochondria are an important source of toxic oxygen radicals in blue light-exposed RPE cells and may indicate new approaches for treating AMD using mitochondria-targeted antioxidants.
The purpose of this study was to measure intrapulpal temperature rise induced by two kinds of bleaching gels when the tooth was exposed to a variety of light-curing units and a diode laser in vitro. The root portions of 80 extracted intact human maxillary central incisors were sectioned with a carborundum disk approximately 2 mm below the cementoenamel junction perpendicular to the long axis of the teeth. Two bleaching agents containing heat-enhancing colorant was applied to the labial surface. Light-curing units used were a conventional halogen (40 s), a high-intensity halogen (30 s), a light-emitting diode unit (40 s), and a diode laser (15 s). The temperature rise was measured in the pulpal chamber with a J-type thermocouple wire that was connected to a data logger. Ten specimens were used for each system and bleaching-agent combination. Differences between the starting temperature and highest temperature reading were taken and the calculated temperature changes were averaged to determine the mean value in temperature rise. Temperature rise values were compared using two-way analysis of variance (ANOVA) at a preset alpha of 0.05. Temperature rise varied significantly depending on curing unit and diode laser used. The diode laser induced significantly higher temperature increases than any other curing unit (11.7 degrees C). The light-emitting diode unit produced the lowest temperature changes (6.0 degrees C); however, there were no statistically significant differences among the curing units and there were no statistically significant differences between bleaching agents. Light activation of bleaching materials with diode laser caused higher temperature changes as compared to other curing units and the temperature rise detected was viewed as critical for pulpal health.
BACKGROUND; Recent technological advances have resulted in the marketing of high-powered, or HP, battery-operated light-emitting diode, or LED, dental curing lights. The authors examine the curing efficiency and peak polymerization temperature, or Tp, of a new HP LED curing light.
The authors studied four visible light-curing, or VLC, units: HP LED (A), first-generation LED (B), conventional halogen (C) and high-intensity halogen (D). They determined the depth of cure, or DOC; adhesion; and Tp of three types of VLC resin-based composites after exposure to each light. The exposure times for units A and D were one-half those for units B and C.
The power density of unit A was 1,000 milliwatts per square centimeter, which was comparable to that of unit D with turbo charge. The DOC and adhesion attained for all three resin-based composites after being light cured by unit A for a 10-second exposure time were equivalent to those after being light cured by unit D for a 10-second exposure time and to those after being light cured by units B and C for 20-second exposure times. The resin-based composites light cured by unit A attained significantly lower Tps than did those light cured by unit D at equivalent cure, or exposure, times and by unit C at twice the cure time.
The authors found that Unit A effectively cured the resin-based composites at one-half the cure time of units B and C and at the same time as unit D, while maintaining low Tp.
The battery-operated HP LED curing light might be an effective, time-saving alternative for clinicians to use in light curing resin-based composites.
Free monomers including triethylene glycol dimethacrylate (TEGDMA) are released by resin composite. Recent studies in vitro have demonstrated that TEGDMA induced GSH depletion and production of radical oxygen species (ROS) in human gingival fibroblasts (HGF) but the exact mechanism of these events remains unclear. Our purpose is to investigate the origin of ROS production. TEGDMA induces a rapid (within 30 min) and drastic depletion of ATP concomitant with the GSH depletion. After 3h incubation, TEGDMA induced an increase of lipid peroxidation associated with LDH leakage. Our data also showed that TEGDMA produced damage at mitochondrial level. This is demonstrated by the collapse of mitochondrial membrane potential (MMP) in HGF treated with TEGDMA. The protective effect of carbonylcyanide m-chlorophenylhydrazone (CCCP), an uncoupler of oxidative phosphorylation on lipid peroxidation and LDH leakage suggests that mitochondria can be implicated in these events. Trolox, a soluble derivative of Tocopherol, weakly prevents ATP but not GSH depletion and totally protects the cells against lipid peroxidation, MMP collapse and cell death. Thus, the present results suggest that TEGDMA induces lipid peroxidation and mitochondrial damage, which contribute to cell death.
The aim of the present study was to test the hypothesis that the use of a light curing unit (LCU) with high light power would result in a higher temperature and therefore a statistically significant lower number of living human gingiva fibroblasts within a pulp chamber model than the use of a light emitting diode (LED) LCU.
The composites Admira, Grandio, Filtek Supreme and Filtek Z250 were polymerized with the LCUs Swiss Master Light, Optilux 501 and an LED LCU prototype in a mould on top of a pulp chamber model. The temperature was recorded within the pulp chamber with a thermocouple. The cytotoxicity of the polymerized samples was tested by using the MTT test.
In general there was no considerable difference in the temperature increase within the pulp chamber model for the different LCUs and composites. There was no statistically significant difference in the cell number (p=0.3767) when the different LCUs were used.
Using a high power halogen LCU for a short time or a standard halogen or LED LCU for a longer time did not result in a considerable difference in the temperature increase or the number of living cells within a pulp chamber model. This study indicates not only that the temperature may have an effect on the living cells, but also that cells may be negatively affected by the unpolymerized composite or light of the LCUs.
Oral and systemic cells are permanently exposed to various types of xenobiotics, such as dental restorative materials, which may subsequently cause adverse effects. Objective of the present investigation was to analyze the effects of three important resin monomers on the glutathione metabolism of human gingival fibroblasts after an incubation period of 4h.
Cells were exposed to various concentrations of 2-hydroxyethyl methacrylate (HEMA; 0.1-10 mM), triethylene-glycol dimethacrylate (TEGDMA; 0.05-2.5 mM), and urethane dimethacrylate (UDMA; 0.005-0.25 mM). Subsequently, cellular glutathione (GSH) concentrations were determined after a treatment period of 4h using the monobromobimane assay. Data were statistically evaluated using Tukey ANOVA with p<0.05.
GSH depletion was dependent on the type of the resin monomer: UDMA>TEGDMA>HEMA. The concentrations for a 50%-reduction of cellular GSH varied between 0.1 mM (0.05 mM) (UDMA), 0.33 mM (0.09 mM) (TEGDMA), and 1.6 mM (0.8 mM) (HEMA). Simultaneously, no decrease of cell numbers was found at any tested concentration.
These data indicate that the investigated resins may cause cell damage due to depletion of intracellular GSH level even at low concentrations within a short period of time. The decrease of GSH is an early reaction, which is triggered prior to other cytotoxic alterations.
Previous investigations have shown that 2-hydroxyethyl methacrylate (HEMA) causes reactive oxygen species (ROS) production, which in turn affects cell survival and cell death. The purpose of this study was to evaluate the effects of the antioxidant N-acetyl-L-cysteine (NAC) on HEMA-induced toxicity in human primary gingival fibroblasts (HGF). HGF were treated with various concentrations of HEMA (0-12 mm) in the absence and presence of NAC (1, 5, and 10 mm). The 3-(4,5 dimethyiazol-2-1)-2-5-diphenyl tetrazolium bromide (MTT) assay was used to evaluate the mitochondrial dehydrogenase activity after HEMA exposure. Viability and cell death were determined by flow cytometry using Annexin V and PI staining. ROS production was detected by the increasing fluorescence of the oxidation-sensitive dye 2',7'-dichlorofluorescein diacetate (DCFH-DA) after HEMA treatment. After a 24h incubation period, HEMA concentrations higher then 10mm caused a decrease of cell viability, mitochondrial activity, and an increase of cell death. HEMA concentrations of 4-12 mm markedly increased ROS levels in a dose-dependent manner. High NAC concentrations (5 and 10 mm) significantly reduced cell death, and restored the mitochondrial activity after a 24 h co-treatment, but 1 mm NAC increased HEMA toxicity (p<0.05). All NAC concentrations significantly reduced ROS levels induced by HEMA after a 2 h exposure (p<0.05), but no such reduction was observed after a 4 h treatment. Furthermore, treatment with 10 mm HEMA and 1 mm NAC for 6h caused an increase in ROS levels compared to 10 mm HEMA alone (p<0.05). In conclusion, our results suggest that high NAC concentrations protect HGF against HEMA cytotoxicity by reducing the induced ROS levels.
Blue light from dental photopolymerization devices has significant biological effects on cells. These effects may alter normal cell function of tissues exposed during placement of oral restorations, but recent data suggest that some light-induced effects may also be therapeutically useful, for example in the treatment of epithelial cancers. Reactive oxygen species (ROS) appear to mediate blue light effects in cells, but the sources of ROS (intra- versus extracellular) and their respective roles in the cellular response to blue light are not known. In the current study, we tested the hypothesis that intra- and extracellular sources of blue light-generated ROS synergize to depress mitochondrial function. Normal human epidermal keratinocytes (NHEK) and oral squamous cell carcinoma (OSC2) cells were exposed to blue light (380-500 nm; 5-60 J/cm(2)) from a dental photopolymerization source (quartz-tungsten-halogen, 550 mW/cm(2)). Light was applied in cell-culture media or balanced salt solutions with or without cells present. Intracellular ROS levels were estimated using the dihydrofluorescein diacetate (DFDA) assay; extracellular ROS levels were estimated using the leucocrystal violet assay. Cell response was estimated using the MTT mitochondrial activity assay. Blue light increased intracellular ROS equally in both NHEK and OSC2. Blue light also increased ROS levels in cell-free MEM or salt solutions, and riboflavin supplements increased ROS formation. Extracellularly applied ROS rapidly (50-400 muM, <1 min) increased intracellular ROS levels, which were higher and longer-lived in NHEK than OSC2. The type of cell-culture medium significantly affected the ability of blue light to suppress cellular mitochondrial activity; the greatest suppression was observed in DMEM-containing or NHEK media. Collectively, the data support our hypothesis that intra- and extracellularly generated ROS synergize to affect cellular mitochondrial suppression of tumor cells in response to blue light. However, the identity of blue light targets that mediate these changes remain unclear. These data support additional investigations into the risks of coincident exposure of tissues to blue light during material polymerization of restorative materials, and possible therapeutic benefits.
To review current knowledge of tooth whitening with respect to external bleaching methods.
The scope is the external bleaching of vital teeth and focuses on mechanisms; in vivo and in vitro measurement methods, and factors influencing the efficacy of the whitening process.
"Medline" and "ISI Web of Science" databases from 1966 and 1974, respectively were searched electronically with key words tooth, teeth, colo*r, white*, bleach* and peroxide.
The importance of tooth whitening for patients and consumers has seen a dramatic increase in the number of products and procedures over recent years, with a concomitant rise in publications on this topic. Literature suggests that the mechanisms of tooth whitening by peroxide occur by the diffusion of peroxide through enamel to cause oxidation and hence lightening of coloured species, particularly within the dentinal regions. A number of approaches are available for measuring changes in tooth colour. These include visual measurements by trained clinicians and instrumental measurements using spectrophotometry, chromameters and digital image analysis. The key factors that affect tooth whitening efficacy by peroxide containing products are concentration and time. In general, higher concentrations are faster than lower concentrations. However, lower concentrations can approach the efficacy of higher concentrations with extended treatment times. Alternative bleach systems to peroxide have received only minor attention. The efficacy of light activated systems versus non-light activated controls in clinical studies is limited and conflicting. Other factors which can influence tooth bleaching outcome include type of stain, initial tooth colour and subject age.
Oral manifestations of Down syndrome include high susceptibility to gingival inflammation with early onset and rapidly progressive periodontitis. The influence of reactive oxygen species (ROS) on periodontitis of Down syndrome is unclear. The aim of this study was to characterize ROS formation in Down syndrome-gingival fibroblasts (DS-GF) using electron spin resonance (ESR) spin trapping with 5,5-dimetyl-1-pyrolline-N-oxide (DMPO), and to determine whether ROS generation plays a role in the pathogenesis of periodontitis in Down syndrome patients. We observed formation of the DMPO-OH spin adduct, indicating HO* generation from cultured DS-GF and non-DS-GF. The increased HO* generation in cultured DS-GF was strongly decreased in the presence of the H2O2 scavenger, catalase, or the iron chelator, desferal. This may due to the enzymatic ability of over-expressed CuZn-superoxide dismutase in Down syndrome to catalyze the formation of H2O2 from O2*-, thereby increasing the availability of substrate H2O2 for the iron-dependent generation of HO* via the Fenton reaction, suggesting that HO* generated from DS-GF may be involved in progressive periodontitis of Down syndrome.
External bleaching procedures utilizing highly concentrated 30-35% hydrogen peroxide solutions or hydrogen peroxide releasing agents can be used for tooth whitening. To enhance or accelerate the whitening process, heat-activation of the bleaching agent by light, heat or laser is described in the literature. The aim of the present review article was to summarize and discuss the available information concerning the efficacy, effects and side effects of activated bleaching procedures.
Information from all original scientific full papers or reviews listed in PubMed or ISI Web of Science (search term: (bleaching OR brightening OR whitening OR colour) AND (light OR laser OR heat OR activation)) were included in the review.
Existing literature reveals that activation of bleaching agents by heat, light or laser may have an adverse effect on pulpal tissue due to an increase of intra-pulpal temperature exceeding the critical value of 5.5 degrees C. Available studies do not allow for a final judgment whether tooth whitening can either be increased or accelerated by additional activation.
Therefore, application of activated bleaching procedures should be critically assessed considering the physical, physiological and patho-physiological implications.
Bleaching Techniques in Restorative Dentistry: An Illustrated Guide
- L Greenwall
- G Fredman
- V V Gordan
L. Greenwall, G. Fredman, V.V. Gordan, Bleaching Techniques in Restorative Dentistry: An Illustrated Guide, Martin Dunitz, 2001.
The role of oxidative stress in the pathogenesis of age-related macular degeneration
- Beatty