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Topical glycolic acid enhances photodamage by ultraviolet light
Abstract
Alpha-hydroxy acids (AHAs) are widely used as ingredients in cosmetics. Several studies suggest that AHAs can increase the sensitivity of skin to ultraviolet (UV) light.
This study was performed in order to determine whether short-term dermal treatment with glycolic acid, a representative AHA, can enhance the damaging effects of UV light. The duration of the effect of AHAs on the sensitivity of skin to UV light was also examined.
The backs of 29 Caucasian subjects were treated, once daily, 6 days per week with either 10% glycolic acid (pH 3.5) or placebo in a randomized double-blinded study. At the end of 4 weeks, sites within each treated area were exposed to 1.5 MED of UV light, determined on previously untreated skin. Specimens were obtained for enumeration of sunburn cells (SBCs) in the first group of subjects (n = 16), whereas cyclobutyl pyrimidine dimers (CPDs) in DNA were determined in the second group (n = 13). The minimal erythema dose (MED) in each site was also determined in the first group of subjects. Sunburn cells and MEDs were re-evaluated in the first group 1 week after discontinuing AHA applications.
Glycolic acid caused enhanced sensitivity to UV light measured as increased SBC induction and lowered MEDs. Cyclobutyl pyrimidine dimers were elevated but not to a statistically significant level. No differences in SBCs or MEDs were evident after a week of discontinued treatments.
Short-term application of 10% glycolic acid sensitizes the skin to the damaging effects of UV light. This photosensitivity is reversed within a week of terminating treatments.
... Reports have demonstrated that AHAs can prevent ultraviolet (UV)-induced skin tumor development [5], and many dermatologists have suggested that AHAs may also play other roles, such as antioxidant activity [6]. However, other scholars hold opposing views and have published studies that refute these assertions; studies have indicated that topical application of AHAs can increase the photosensitivity of skin to UVB-irradiation When paired with sunlight exposure, and AHAs also induced uneven skin pigmentation [1,7]. The question of whether AHAs are a friend or foe of the skin remains. ...
... Apoptosis and efficient repair mechanisms of DNA damage protect human keratinocytes against UVB [21]. One study determined that that topical application of 10% GA for 12 weeks increased the sensitivity of the skin to UV light and enhanced the formation of sunburn cells (SBCs) [7]. Our previous study demonstrated that cotreatment of AHAs with a high concentration of GA (5 mM) and UVB had a synergistic effect on apoptosis in human keratinocyte HaCaT cells [9]. ...
... A well-known major cause of skin aging is chronic microinflammation triggered by UV irradiation and external pollutants [41]. Many studies have demonstrated that peeling can increase the sensitivity of the skin to UV light, and even more have indicated that UV light combined with AHA-associated peeling leads to more serious skin damage [7]. Lask et al. (2005) reported that patients treated with GA (20-50%) every other day for the removal of the keratin layer experienced serious UV damage [41]. ...
AHAs are organic acids with one hydroxyl group attached to the alpha position of the acid. AHAs including glycolic acid, lactic acid, malic acid, tartaric acid, and citric acid are often used extensively in cosmetic formulations. AHAs have been used as superficial peeling agents as well as to ameliorate the appearance of keratoses and acne in dermatology. However, caution should be exercised in relation to certain adverse reactions among patients using products with AHAs, including swelling, burning, and pruritus. Whether AHAs enhance or decrease photo damage of the skin remains unclear, compelling us to ask the question, is AHA a friend or a foe of the skin? The aim of this manuscript is to review the various biological effects and mechanisms of AHAs on human keratinocytes and in an animal model. We conclude that whether AHA is a friend or foe of human skin depends on its concentration. These mechanisms of AHAs are currently well understood, aiding the development of novel approaches for the prevention of UV-induced skin damage.
... On the contrary, photo-protective, anti-inflammatory effects and anti-oxidant effects of topical GA treatment on UVBirradiated skin have been reported [3,4]. However, it has been concerned that topical application of GA can increase photosensitivity of skin to ultraviolet radiation [5,6]. The US Food and Drug Administration gave caution to the adverse reactions including redness, swelling, burning, and puritus from people using AHAs products [7]. ...
... The US Food and Drug Administration gave caution to the adverse reactions including redness, swelling, burning, and puritus from people using AHAs products [7]. It was demonstrated that topical application of 10% GA may enhance photodamage by UV light in human subjects, which led to the speculation that a subclinical irritation may contribute to photosensitivity induced by topical application of GA [5]. Kornhauser et al. investigated that GA can increase the sensitivity of human skin to solar simulated radiation (SSR) [6]. ...
... It has been known that sunburn cells (SBCs) are keratinocytes undergoing apoptosis after UVB irradiation [6,16,17], and GA has effect to induce SBC formation by investigators [5,6]. Kaidbey et al. prescribed 10% GA, 6 days per week for 4 weeks, in 16 subjects and found that GA enhanced phototoxicity as revealed by increased SBC formation and lowered the minimal erythema dose (MED) [5]. ...
Background:
Glycolic acid (GA) has been widely used in cosmetic agents and superficial chemical peeling in recent years. It has long been concerned that UV irradiation would enhance the photosensitivity of GA on human skin. Therefore, it is mandatory to explore the biologic effects of concomitant exposure of GA and UV irradiation in human keratinocytes.
Objective:
The aim of the study is to explore the effects of concomitant exposure of GA and UVB in a human keratinocyte cell line (HaCaT).
Methods:
We used HaCaT to investigate the effects of GA (5mM), UVB (50mJ/cm(2)), and co-treatment with GA and UVB (GA+UVB) in human keratinocytes. We used a phase contrast microscope to observe morphological changes of the cells, and employed flow cytometry to detect cell viability, cell cycle, and mitochondrial membrane potential (MMP), and intracellular reactive oxygen species (ROS) levels. Cell damage was detected by DAPI stain, and Western blot was used to detect the activities of apoptosis- related and cycle checkpoint-related proteins such as Bax, Bcl-2, caspases-3, -4, -9, Endo G, AIF, and p21, p27, p53, cdk2, cyclin E, cyclin A.
Results:
We found that either GA or UVB alone had inhibitory effect on cell proliferation, and co-treatment with GA and UVB had synergistic anti-proliferative effect. GA alone did not affect the cell cycle, and UVB induced HaCaT cells accumulated at S phase, and co-treatment with GA and UVB arrested cells at S phase more prominently. Moreover, all the treatment with GA, UVB, and GA+UVB in HaCaT cells induced apoptosis. We further demonstrated that GA had synergistic apoptotic effect in human keratinocytes. GA and UVB both had effects on the decline of MMP and increase of ROS release, and GA had synergistic increase in the level of ROS in UVB-treated HaCaT cells. Besides, co-treatment with GA and UVB had synergistic effect on apoptosis through the over-expressions of Bax, p21, p53, caspases-3, -4, -9, Endo G and AIF, and confocal microscopy disclosed translocation of AIF and Endo G from cytoplasm to the nucleus. Therefore, apoptosis induced by co-treatment by GA+UVB was initiated and executed by multiple pathways including mitochondria- and ER-dependent, and caspase-dependent and caspase-independent pathways.
Conclusion:
We demonstrated that GA, UVB, GA+UVB inhibited proliferation and induced apoptosis in HaCaT cells. The mechanisms of apoptosis induced by co-treatment of GA and UVB involve multiple pathways. The synergistic photo-toxicity may be related to cell cycle arrest and apoptosis in UVB-treated HaCaT cells. These results highlight the potential adverse effects of GA-containing cosmetic agents on human skin.
... Lately, glycolic and lactic acids have been reported to affect barrier function integrity, possibly interfering with skin absorption of other cosmetic ingredients, and enhancing potential photodamage to the skin from ultraviolet light exposure, including lowering of the Minimal Erythema Dose (MED), increased sunburn cell (SBC) formation, and/or elevated cyclobutane pyrimidine dimers (CPDs) indicative of DNA damage (Kaidbey et al., 2003;Kornhauser et al., 2009;SCCNFP, 2000SCCNFP, , 2004US FDA, 2005). Increased SBC production and lowered MED were observed after repeated topical treatment with 10% glycolic acid (pH 3.5) followed by exposure to simulated solar radiation (Kaidbey et al., 2003;Kornhauser et al., 2009). ...
... Lately, glycolic and lactic acids have been reported to affect barrier function integrity, possibly interfering with skin absorption of other cosmetic ingredients, and enhancing potential photodamage to the skin from ultraviolet light exposure, including lowering of the Minimal Erythema Dose (MED), increased sunburn cell (SBC) formation, and/or elevated cyclobutane pyrimidine dimers (CPDs) indicative of DNA damage (Kaidbey et al., 2003;Kornhauser et al., 2009;SCCNFP, 2000SCCNFP, , 2004US FDA, 2005). Increased SBC production and lowered MED were observed after repeated topical treatment with 10% glycolic acid (pH 3.5) followed by exposure to simulated solar radiation (Kaidbey et al., 2003;Kornhauser et al., 2009). Based on the data reviewed at the time, the Scientific Committee on Cosmetic Products and Non-Food Products (SCCNFP) recommended levels of lactic acid and glycolic acid be restricted in cosmetic products to 62.5% (pH P 5.0) and 64% (pH P 3.8), respectively (SCCNFP, 2000). ...
... Also postulated is the potential alteration of the physical properties of the epidermis and dermis by the moisturizing and exfoliating effects of glycolic acid that could affect scattering and absorption of ultraviolet radiation, playing a role in the increased sensitivity of the skin (Kornhauser et al., 2009;Yu and Van Scott, 2004). Glycolic acid-induced subclinical (i.e., nonerythematous) skin irritation may also contribute to the increased photosensitivity of skin exposed to such formulations (Hruza and Pentland, 1993;Kaidbey et al., 2003;Zhuang et al., 2000). Furthermore, some formulations containing high levels of AHAs have the potential to be intermittently used over an extended period of time, often for years or decades, resulting in extensive exposure to these chemicals. ...
Alpha-hydroxy acids (AHAs), primarily glycolic and lactic acids, are widely used in cosmetics to alleviate dyspigmentation, photodamage, and other aging skin conditions and as pH adjusters. Glycolic acid reportedly enhances skin damage after repeated ultraviolet light exposure, e.g., increased sunburn cell formation. This study assessed potential in vitro skin penetration of lactic acid and malic acid incorporated into rinse-off personal care products, compared with rinse-off and leave-on exposures to glycolic acid (10%, pH 3.5) in a reference lotion. Radiolabeled AHA-fortified shampoo, conditioner, and lotion were evenly applied as single doses to human epidermal membranes mounted in static diffusion cells (not occluded). Exposures were 1-3 min (rinse-off) or 24 h (leave-on). Epidermal penetration of malic acid and lactic acid from the rinse-off shampoo and conditioner, respectively, was negligible, with >99% removed by rinsing, a negligible portion remaining in the stratum corneum (≤0.15%), and even less penetrating into the viable epidermis (≤0.04%). Glycolic acid penetration from the leave-on reference lotion was 1.42 μg equiv./cm2/h, with total absorbable dose recovery (receptor fluid plus epidermis) of 2.51%, compared to 0.009%, 0.003%, and 0.04% for the rinse-off reference lotion, shampoo (malic acid), and conditioner (lactic acid) exposures, respectively. Dermal penetration of AHAs into human skin is pH-, concentration-, and time-dependent. Alpha-hydroxy acids in rinse-off shampoos and conditioners are almost entirely removed from the skin within minutes by rinsing (resulting in negligible epidermal penetration). This suggests that ultraviolet radiation-induced skin effects of AHA-containing rinse-off products are negligible.
... The use of glycolic acids in chemical peeling is strictly correlated with some undesirable side effects such as persistent erythema and pruritus, burning, post-infl ammatory hyper/ hypopigmentation, hypertrophic scarring, and infectious complications (3,11,12). Moreover, recent experimental studies demonstrate that short-term application of glycolic acid sensitizes the skin to the damaging effects of UV light (13). To improve the safety of products, committees set up by associations of cosmetics manufacturers in Europe and in the USA recommend similar guidelines and, in particular, pH values higher than 3.5 and alpha-hydroxy acids contents lower than 7-10% (14). ...
... On the other hand, since the chemical peeling produces an insult to the skin, several side effects, such as erythema and redness, develop after treatment with exfoliating agents (3,9). Moreover, recent studies report that short-term dermal exposure with low concentrations of exfoliating agents results in increased photosensitivity to UV light, measured as increased erythema and tanning (13,24). Skin tolerance to the exfoliating treatment is usually assessed by a visual and subjective record system. ...
... Recent experimental studies have demonstrated that subclinical irritation may be associated with topical exposure to glycolic acid. It is conceivable that the pro-infl ammatory mediators released in irritated skin can affect events leading to UV-light sensitivity (13), increasing the risks of acute and chronic skin reactions. However, it is important to note that the rapid penetration of glycolic acid induces a more rapid skin exfoliation but causes a more intense skin redness and irritation. ...
The aim of the present study was to compare the effectiveness and the safety of different topical agents (glycolic acid, mandelic acid, and grape juice acid mixture) in skin exfoliation by objective instrumental methods. To evaluate the exfoliating effects of these substances, a new experimental in vivo protocol based on DHA (dihydroxyacetone)-induced skin pigmentation was used. Skin acceptability towards acid application was investigated by the evaluation of skin erythema induced by topical application of these substances at increased concentrations. Furthermore, their photosensitizing effects were evaluated by determining the increase in sensitivity to UV-light exposure in cutaneous sites previously treated with acids. These in vivo evaluations were monitored by reflectance spectophotometry. From the results obtained, we observed the differing capacities of the tested acids to increase the rate of skin regeneration, with a significant reduction in the time required to obtain skin renewal. The study pointed out that glycolic acid (10% w/w) induced a faster skin exfoliation, a more intense erythema, and a higher photosensitizing effect in comparison with the mandelic acid and grape juice acid mixtures. Further evidence showed that the mandelic acid and grape juice acid mixtures were able to induce a slower and safer peeling action in comparison with glycolic acid. Finally, our results suggest that the methodologies and protocols used in this study may help in choosing the most appropriate topical agents for skin exfoliating treatments.
... Questions have been raised about the safety of prolonged use of HA-containing products on sun-exposed skin. A number of clinical studies have reported that topical application of glycolic acid can increase the skin's sensitivity to solar simulated radiation (SSR) [4,5], however most of these studies used vehicles which differ significantly from those used in cosmetic products. In addition, a single cutaneous marker for UV-induced damage was usually measured. ...
... In addition, a single cutaneous marker for UV-induced damage was usually measured. In the few cases in which multiple endpoints were used, they were not evaluated in the same subjects [4]. In 1998, the Cosmetic Ingredient Review Expert Panel evaluated the available studies [6] and concluded that αHA ingredients are not mutagenic or carcinogenic, are not reproductive or developmental toxins, and are not skin sensitizers. ...
... SBCs were counted in a blinded manner in approximately 16 sections cut at 50 μm intervals from each specimen. The average number of SBCs was calculated from a minimum of 70 high power fields in each biopsy at 400× magnification [4]. ...
alpha-Hydroxy acids (alphaHAs) are reported to reduce signs of aging in the skin and are widely used cosmetic ingredients. Several studies suggest that alphaHA can increase the sensitivity of skin to ultraviolet radiation. More recently, beta-hydroxy acids (betaHAs), or combinations of alphaHA and betaHA have also been incorporated into antiaging skin care products. Concerns have also arisen about increased sensitivity to ultraviolet radiation following use of skin care products containing beta-HA.
To determine whether topical treatment with glycolic acid, a representative alphaHA, or with salicylic acid, a betaHA, modifies the short-term effects of solar simulated radiation (SSR) in human skin.
Fourteen subjects participated in this study. Three of the four test sites on the mid-back of each subject were treated daily Monday-Friday, for a total of 3.5 weeks, with glycolic acid (10%), salicylic acid (2%), or vehicle (control). The fourth site received no treatment. After the last treatment, each site was exposed to SSR, and shave biopsies from all four sites were obtained. The endpoints evaluated in this study were erythema (assessed visually and instrumentally), DNA damage and sunburn cell formation.
Treatment with glycolic acid resulted in increased sensitivity of human skin to SSR, measured as an increase in erythema, DNA damage and sunburn cell formation. Salicylic acid did not produce significant changes in any of these biomarkers.
Short-term topical application of glycolic acid in a cosmetic formulation increased the sensitivity of human skin to SSR, while a comparable treatment with salicylic acid did not.
... It has been suggested that topical application of glycolic acid can increase the photosensitivity of skin to ultraviolet radiation (Andersen, 1998;Kaidbey et al., 2003). Glycolic acid was demonstrated to inhibit UVinduced skin tumor development in hairless mouse (Hong et al., 2001). ...
... They further suggested that glycolic acid may exert the inhibitory effect on the UVB-induced skin tumor development by blocking the UVB-induced apoptosis through inhibition of c-fos expression and activation of AP-1 in addition to the inhibition of p53-p21 response pathway (Ahn et al., 2002). However, other studies had shown that even short-term topical application of 10% glycolic acid may enhance photodamage by UV light in human subjects (Andersen, 1998;Kaidbey et al., 2003), which prompt the speculation that a subclinical irritation may contribute to photosensitivity induced by topical application of glycolic acid (Kaidbey et al., 2003). It is still obscure whether glycolic acid enhances or decreases photodamage of the skin. ...
... They further suggested that glycolic acid may exert the inhibitory effect on the UVB-induced skin tumor development by blocking the UVB-induced apoptosis through inhibition of c-fos expression and activation of AP-1 in addition to the inhibition of p53-p21 response pathway (Ahn et al., 2002). However, other studies had shown that even short-term topical application of 10% glycolic acid may enhance photodamage by UV light in human subjects (Andersen, 1998;Kaidbey et al., 2003), which prompt the speculation that a subclinical irritation may contribute to photosensitivity induced by topical application of glycolic acid (Kaidbey et al., 2003). It is still obscure whether glycolic acid enhances or decreases photodamage of the skin. ...
Apoptosis is a particular process that leads to the programmed cell death, and it has been a potentially therapeutic target of cancer. In this study, we evaluated the possible apoptotic effects of glycolic acid on human leukemia cell line (HL-60) in vitro. The morphological changes, cell viability, apoptosis induction, and caspase-3 activity were measured by phase microscopy, flow cytometry, and Western blot analysis. Morphological changes including shrinkage of cells were clearly demonstrated in HL-60 cells treated with increasing concentrations of glycolic acid. Cell viability was significantly affected by glycolic acid treatment in a dose- and time-dependent manner. In comparison to the control group, glycolic acid treatment had a profound effect in the induction of apoptosis by flow cytometric assays. In the cell cycle analysis, glycolic acid caused the increased percentage of cells in G2/M phase and the decreased expression of the cyclin A and cyclin B1, suggesting the induction of G2/M arrest of cell cycle by glycolic acid. Moreover, glycolic acid treatment promoted caspase-9 and -3 activity in a dose-dependent manner, but caspse-8 activity was not affected during the same process. Glycolic acid co-administrated with broad-spectrum caspase inhibitor, z-VAD-fmk, caspase-3 activity was blunted and apoptosis was also markedly blocked in HL-60 cells. In conclusion, glycolic acid-induced apoptosis in HL-60 cells may be through the activation of caspase-3. Future studies focusing on cell signaling and biological significance of glycolic acid-induced apoptosis would lead to exploring the mechanisms of chemotherapeutic potency of glycolic acid in human cancers.
... The age range of our study participants was 12 to 19 years with a mean age of 16.3 (±1.48) years. The most represented age group was the [16][17][18][19] year group. The students in Form five constituted the majority class in our sample 31.6% ...
... Although AHA are natural compounds, caution is recommended when using them because of their undesirable effects such as oedema, burns, pruritus and dry skin. Furthermore, their role in worsening photoinduced skin damage is currently becoming more evident, with consequent occurrence of carcinomatous lesions [18]. ...
Introduction: Youths, particularly teenagers in Africa are the target of the growing cosmetics market especially skin-lightening cosmetic products (SLCPs). With an increasing demand, the African adolescent in urban areas is susceptible to engage in skin bleaching (SB). However, little is known about the perceptions of youths on this practice. The objective of our study was to determine the practice of SB and evaluate the perception of users of SLCPs on SB and its complications.
... In vivo human study There are three reports (11)(12)(13) which showed that pretreatment of peeling agents increases UV sensitivity (Table 1). Kaidbey et al. (11) reported that pretreatment with 10% glycolic acid (GA, pH3.5) once daily, 6 days ⁄ week resulted in an increase of sunburn cell (SBC) formation and cyclobutane pyrimidine dimers (CPDs) as well as lowering minimal erythematous dose (MED). ...
... In vivo human study There are three reports (11)(12)(13) which showed that pretreatment of peeling agents increases UV sensitivity (Table 1). Kaidbey et al. (11) reported that pretreatment with 10% glycolic acid (GA, pH3.5) once daily, 6 days ⁄ week resulted in an increase of sunburn cell (SBC) formation and cyclobutane pyrimidine dimers (CPDs) as well as lowering minimal erythematous dose (MED). This change, however, was recovered after a week of discontinued treatments, which means that this enhanced UV sensitivity is tentative and reversal. ...
Chemical peeling is one of the dermatological treatments available for certain cutaneous diseases and conditions or improvement of cosmetic appearance of photoaged skin. However, it needs to be clarified whether the repetitive procedure of chemical peeling on photodamaged skin is safe and whether the different chemicals used for peeling results in similar outcomes or not. In this article, we reviewed the effect of peeling or peeling agents on the skin in relation to ultraviolet (UV) radiation. The pretreatment of peeling agents usually enhance UV sensitivity by inducing increased sunburn cell formation, lowering minimum erythematous dose and increasing cyclobutane pyrimidine dimers. However, this sensitivity is reversible and recovers to normal after 1-week discontinuation. Using animals, the chronic effect of peeling and peeling agents was shown to prevent photocarcinogenesis. There is also an in vitro study using culture cells to know the detailed mechanisms of peeling agents, especially on cell proliferation and apoptotic changes via activating signalling cascades and oxidative stress. It is important to understand the effect of peeling agents on photoaged skin and to know how to deal with UV irradiation during the application of peeling agents and treatment of chemical peeling in daily life.
... In vivo human study There are three reports (11)(12)(13) which showed that pretreatment of peeling agents increases UV sensitivity (Table 1). Kaidbey et al. (11) reported that pretreatment with 10% glycolic acid (GA, pH3.5) once daily, 6 days ⁄ week resulted in an increase of sunburn cell (SBC) formation and cyclobutane pyrimidine dimers (CPDs) as well as lowering minimal erythematous dose (MED). ...
... In vivo human study There are three reports (11)(12)(13) which showed that pretreatment of peeling agents increases UV sensitivity (Table 1). Kaidbey et al. (11) reported that pretreatment with 10% glycolic acid (GA, pH3.5) once daily, 6 days ⁄ week resulted in an increase of sunburn cell (SBC) formation and cyclobutane pyrimidine dimers (CPDs) as well as lowering minimal erythematous dose (MED). This change, however, was recovered after a week of discontinued treatments, which means that this enhanced UV sensitivity is tentative and reversal. ...
Chemical peeling is one of the dermatological treatments available for certain cutaneous diseases and conditions or improvement of cosmetic appearance of photoaged skin. However, it needs to be clarified whether the repetitive procedure of chemical peeling on photodamaged skin is safe and whether the different chemicals used for peeling results in similar outcomes or not. In this article, we reviewed the effect of peeling or peeling agents on the skin in relation to ultraviolet (UV) radiation. The pretreatment of peeling agents usually enhance UV sensitivity by inducing increased sunburn cell formation, lowering minimum erythematous dose and increasing cyclobutane pyrimidine dimers. However, this sensitivity is reversible and recovers to normal after 1-week discontinuation. Using animals, the chronic effect of peeling and peeling agents was shown to prevent photocarcinogenesis. There is also an in vitro study using culture cells to know the detailed mechanisms of peeling agents, especially on cell proliferation and apoptotic changes via activating signalling cascades and oxidative stress. It is important to understand the effect of peeling agents on photoaged skin and to know how to deal with UV irradiation during the application of peeling agents and treatment of chemical peeling in daily life.
... Furthermore, only a single cutaneous biomarker for UV-induced damage was usually measured. In the few cases in which multiple endpoints were used, they were not evaluated in the same subject.10 In a previous study using 16 subjects, we reported that 10% glycolic acid, applied 6 days/week for 4 weeks, enhanced the sensitivity to UVB radiation, measured as increased sunburn cell formation, and also lowered the minimal erythemal dose (MED).10 ...
... In the few cases in which multiple endpoints were used, they were not evaluated in the same subject.10 In a previous study using 16 subjects, we reported that 10% glycolic acid, applied 6 days/week for 4 weeks, enhanced the sensitivity to UVB radiation, measured as increased sunburn cell formation, and also lowered the minimal erythemal dose (MED).10 In another cohort group (n = 13), levels of cyclobutane pyrimidine dimers were elevated in αHA-treated skin, but not to a statistically significant level. ...
Hydroxy acids (HAs) represent a class of compounds which have been widely used in a number of cosmetic and therapeutic formulations in order to achieve a variety of beneficial effects for the skin. We review and discuss the most frequently used classes of these compounds, such as α-hydroxy acids, β-hydroxy acids, polyhydroxy acids, and bionic acids, and describe their applications as cosmetic and therapeutic agents. Special emphasis is devoted to the safety evaluation of these formulations, in particular on the effects of their prolonged use on sun-exposed skin. Furthermore, we summarize the very limited number of studies dealing with the modifications evoked by topical application of products containing HAs on photocarcinogenesis. In spite of the large number of reports on the cosmetic and clinical effects of HAs, their biological mechanism(s) of action still require more clarification. Some of these mechanisms are discussed in this article along with important findings on the effect of HAs on melanogenesis and on tanning. We also emphasize the important contribution of cosmetic vehicles in these types of studies. Thus, HAs play an important role in cosmetic formulations, as well as in many dermatologic applications, such as in treating photoaging, acne, ichthyosis, rosacea, pigmentation disorders, and psoriasis.
... Due to the presence of hydroxyl and carboxyl groups, AHAs are well known to possess antioxidant, non-toxicity, and photo-aging properties that reduce wrinkles and protect skin from UV-induced damage. [12][13][14] Furthermore, they are relatively cheap and highly water-soluble, which are convenient for the preparation of carbon dots. However, they are physically and chemically unstable, limiting their capability in commercial products. ...
The exhaustion of the ozone layer in the atmosphere has caused an escalation of dangerous UV radiation penetrating the earth's surface. Reactive oxygen species generated under UV exposure through photocatalytic reactions can lead to severe skin health risks, such as skin cancer and premature aging. Although chemical sunscreens are widely used for protection against UV radiation, their long‐term use poses safety concerns and causes environmental damage. In this regard, we have developed carbon dots (CDs) with excellent UV absorption along with extraordinary antioxidant activity, photostability, and biocompatibility from green tea as the main precursor and alpha‐hydroxy acids (AHA) as the co‐precursors, including gluconic acid (GA), citric acid (CA), and tartaric acid (TA). All CDs have a strong UV absorption, especially in the UVB and UVC regions, with G‐CDs having the highest UV absorption. The G‐CDs also have the highest antioxidant activity, which is also higher than that of their parent green tea, AHAs, and ascorbic acid, a well‐known antioxidant. The photostability and cell viability of the G‐CDs were also excellent. The potential of G‐CDs as multifunctional materials makes them a promising candidate for cosmetic applications, particularly for their ability to absorb UV radiation with exceptionally high antioxidant activity, photostability, and biocompatibility.
... The statement also contains a warning for users to limit sun exposure, use sunscreen, and wear protective clothes, throughout the application of AHAs and for a week after treatment has ceased (Fiume, 2017). Apart from increased phototoxicity, AHAs can cause various other side effects, including redness, swelling, burning, and pruritus (Kaidbey et al., 2003;Tang and Yang, 2018). The Cosmetic Ingredient Review (CIR) Expert Panel, the US self-regulatory body for the cosmetic industry, has concluded that products containing AHAs are safe for use in cosmetic products in concentrations of up to 10% (Fiume, 2017;Kornhauser et al., 2009). ...
Alpha hydroxy acids (AHAs) are used in dermatology for topical treatment of skin disorders. Some regulatory bodies, including Food and Drug Administration (FDA), recommended labeling cosmetic products with sunburn alerts and proposed limitations regarding concentrations of AHAs in cosmetic products. In addition, The Cosmetic Ingredient Review (CIR) Expert Panel recommended 10% of AHAs in products as the maximal safe concentration. With a rapidly increasing trend of online purchasing of cosmetic products, it is important that their labels convey the necessary warnings and that they be harmonized with regulatory bodies regarding the recommended concentrations of AHAs. The aim of this report was to investigate whether or not the sunburn alert, as well as AHA recommendations mostly used for exfoliating cosmetic products, was visible to consumers during the online purchasing. The compliance with FDA and CIR Expert Panel standards was analyzed in the first 50 cosmetic products obtained after the conducted investigation on the Amazon.com e-commerce company website using the search term “AHA anti-aging.” It was found that exfoliating cosmetic products contained AHAs in a broad range of concentrations, from 2.5 up to 70%. Nineteen out of 50 products contained a concentration of AHAs greater than recommended. Twelve products did not contain any data at all regarding the concentration of AHAs. Sunburn alerts were present in 16 out of 50 analyzed product pages. In conclusion, more efforts should be made in providing users with information and the necessity of protection from potential complications after topical AHAs product treatments
... [67][68][69][70] AHA may also induce reversible skin photosensitivity and contact urticaria. 61,71,72 CA and GA (≥3%) can induce apoptosis of keratinocytes that enhances photodamage to the skin. 73 AHA may also decrease melanin deposition in the skin in vivo. ...
Infection preventive practice of using disinfectants against SARS-CoV-2 has become the new normal due to the COVID-19 pandemic. Although disinfectants may not be applied directly to the human body, it remains at high risk of exposure including close skin contact on disinfected surfaces or during handling. This dermal contact, on a regular basis, can induce hazardous skin reactions like irritation, inflammation, and burning in severe conditions. Disinfectants are germicide chemicals that can penetrate the skin and create skin reactions that are usually regarded as irritant and allergic contact dermatitis. More importantly, disinfectants can react with skin components (proteins and lipids) to facilitate their skin penetration and disrupt the skin barrier function. Whereas the antimicrobial actions of disinfectants are well understood, much less is known regarding their dermatologic reactions, including but not limited to irritation and hypersensitivity. We reviewed the skin reactions created by those disinfectants against SARS-CoV-2 approved by the European Chemical Agency and the United States Environmental Protection Agency.
... A clinical study conducted by other investigators evaluated the effects of daily glycolic acid treatment (6 days per week) on the MED, sunburn cells, and cyclobutyl pyrimidine dimers (CPDs). Treatment lasted for 4 weeks, followed by exposure to UV light [21]. Either a 10 % glycolic acid formulation (pH 3.5) or a placebo (formulation without glycolic acid) was applied to the backs of 29 Caucasian volunteers. ...
Cosmetics, a category of consumer products that are sold worldwide, are often referred to as personal care products by industry, to account for some of the diversity of these consumer products. However, not all personal care products marketed in the USA are regulated as cosmetics. This chapter will focus on the use of some categories of personal care products currently marketed to improve the appearance of aging while at the same time discussing the process of how the skin ages, and interventions (not including surgical) by which the appearance of wrinkles may be altered, prevented, or reduced are discussed under more than one regulatory oversight within the USA, such as cosmetics, drugs, or devices. The regulatory authority that has jurisdiction over the specific product categories marketed within the USA is identified and discussed. Specific focus is given to alpha hydroxy acids (AHAs), retinoids, collagen synthesis, moisturizers and skin hydration, sunscreens, hydroquinone, and peels or scrubs, which will embrace the bulk of the products available over the counter (OTC) to consumers. Some products, such as Botox, which are available only through a physician, are also briefly discussed.
... Topical treatment of photo-aging skin with alpha-hydroxy acids (AHA) has been reported to improve wrinkling, roughness, hyperpigmentation, acne, and rosacea within months of daily application [9][10][11][12]. However, AHAs may induce photosensitivity, increase the number of sunburn cells, and decrease the minimal erythema dose [8,[13][14][15]. Although the safety concerns of AHAs were announced by the Ministry of Health and Welfare, R.O.C, chemical peeling agents contained higher concentrations of AHAs (20%-70%) and low pH levels were used in the hospitals and local practitioner's clinics [16,17]. ...
Malic acid (MA) has been commonly used in cosmetic products, but the safety reports in skin are sparse. To investigate the biological effects of MA in human skin keratinocytes, we investigated the potential cytotoxicity and apoptotic effects of MA in human keratinocyte cell lines (HaCaT). The data showed that MA induced apoptosis based on the observations of DAPI staining, DNA fragmentation, and sub-G1 phase in HaCaT cells and normal human epidermal keratinocytes (NHEKs). Flow cytometric assays also showed that MA increased the production of mitochondrial superoxide (mito-SOX) but decreased the mitochondrial membrane potential. Analysis of bioenergetics function with the XF 24 analyzer Seahorse extracellular flux analyzer demonstrated that oxygen consumption rate (OCR) was significantly decreased whereas extracellular acidification rate (ECAR) was increased in MA-treated keratinocytes. The occurrence of apoptosis was proved by the increased expressions of FasL, Fas, Bax, Bid, caspases-3, -8, -9, cytochrome c, and the declined expressions of Bcl-2, PARP. MA also induced endoplasmic reticulum stress associated protein expression such as GRP78, GADD153, and ATF6α. We demonstrated that MA had anti-proliferative effect in HaCaT cell through the inhibition of cell cycle progression at G0/G1, and the induction of programmed cell death through endoplasmic reticulum stress- and mitochondria-dependent pathways.
... 21 In this study, all patients experienced discomforts including burning, stinging, redness, and desquamation; and a few patients had to discontinue due to side effects. It has been recognized that repeated use of glycolic acid products makes skin more sensitive to sun, 22 which may enhance suninduced photodamage 23 and lead to an increase in pigmentation even in the absence of noticeable irritation. 24 The present study has some significant limitations, however. ...
Hyperpigmentation and solar damage remains a difficult problem to treat with topical agents.
To evaluate a novel skin-lightening complex (SLC) comprising four actives targeting melanin formation at multiple levels, namely disodium glycerophosphate, l-leucine, phenylethyl resorcinol, and undecylenoyl phenylalanine, in an oil-in-water emulsion cream. PATIENTS ⁄
Skin-lightening complex was evaluated in 80 female subjects of skin types I-III with at least moderate mottled hyperpigmentation. After a wash-out period of 1 month with a sunscreen, the subjects added a cream containing the SLC for 12 weeks twice daily to entire face and continued the sunscreen use.
Whereas there was no significant change during the wash-out period, the primary endpoint mottled hyperpigmentation decreased by 32% after the 12-week treatment period with the SLC cream. Secondary endpoints such as severity and number of lentigines, skin tone, and skin brightness also improved. In all, 57% of the subjects showed at least a moderate response, 17% did not improve, and 3% got worse after the treatment.
The SLC cream was well tolerated, in particular when comparing with exfoliating or peeling agent containing skin-lightening products. When used with a daily sunscreen, this study confirms that the SLC represents an alternative to hydroquinone, retinoids, and many other skin-lightening actives.
... 30 Treatment with glycolic acid has been shown to result in increased sensitivity of human skin to UV, measured as an increase in erythema, DNA damage, and sunburn cell formation. 31 However, it has been shown that SA does not produce significant changes in any of these biomarkers in human skin; 32 this observation was recently confirmed by Mammone et al. who showed that SA inhibited ultraviolet B (UVB) induced Nuclear Factor Kappa B (NF-kb) activation in keratinocytes, reduced UVB-induced sunburn cell formation, and increased DNA repair. 33 The only other acid that we are aware of that does not induce photosensitivity following UV irradiation is glucanolactone. ...
Anti-aging effects of high concentrations of salicylic acid (SA) peels are commonly known. Like all acids, SA can produce somatosensory and visible irritation to the skin and as such may be unsuitable for subjects with sensitive skin.
To provide evidence that sodium salicylate (SS) obtained from neutralization of 1% SA by sodium hydroxide can deliver significant anti-aging benefits.
The effects of SS were examined using three approaches: (1) evaluating its effects on stimulating the synthesis of fibrillin and collagen-1 in vivo; (2) examining its efficacy by using Fast Optical in vivo Topometry (FOITS) in a double-blind, placebo-controlled clinical study; (3) determining its effects on both expert and naïve grader assessement of wrinkles in a double-blind, placebo-controlled study.
In the first study SS produced significant increases of the fibrillin and collagen-1 anti-aging biomarkers compared with the untreated skin control. A commercially available retinol cream delivered similar effects to SS. In the second study using FOITS we showed that the SS formulation significantly reduced wrinkle depth (Rz) and skin roughness (Ra) after 4 and 8 weeks of daily application vs. placebo (Rz: -8.2 ± 1.40% and -11.4 ± 1.07%; Ra: -7.8 ± 1.33% and -11.9 ± 0.61%; P < 0.01). In the third study reductions in wrinkle depth were observed by expert assessment at both 4 and 8 weeks for the SS-containing formulation compared to its placebo (P < 0.05). Equally, non-expert graders recorded the SS formulation superior to its placebo.
Although the mechanism of action is not completely understood, we believe the benefits of SS are derived from its intrinsic stratum corneum exfoliation effects. All three studies demonstrate the significant anti-aging effects of SS that are especially suitable for subjects with sensitive skin.
... Topical ointment containing 2% 2-hydroxy-5-octanoyl benzoic acid (b-lipohydroxy acid, lipophylic derivative of salicylic acid) has been reported to improve photo-damaged epidermis. 31 Therefore, chemical peeling with glycolic acid and salicylic acid might have the advantage of improving photo-aged skin compared to TCA. However, as was shown in our study, there was no significant difference in the preventive effect on skin carcinogenesis between chemical peeling with 35% glycolic acid, 30% salicylic acid and 10% TCA. ...
Chemical peeling is one of the dermatological treatments available for certain cutaneous diseases and conditions or improvement of cosmetic appearance of photo-aged skin. We assessed the photo-chemopreventive effect of several clinically used chemical peeling agents on the ultraviolet-irradiated skin of hairless mice. Chemical peeling was done using 35% glycolic acid dissolved in distilled water, 30% salicylic acid in ethanol, and 10% or 35% trichloroacetic acid in distilled water at the right back of ultraviolet-irradiated hairless mice every 2 weeks for glycolic acid, salicylic acid and 10% trichloroacetic acid, and every 4 weeks for 35% trichloroacetic acid for a total of 18 weeks after the establishment of photo-aged mice by irradiation with ultraviolet B range light three times a week for 14 weeks at a total dose of 6.66 J/cm(2) . Tumor formation was assessed every week. Skin specimens were taken from treated and non-treated area for evaluation under microscopy, evaluation of p53 expression and mRNA expression of cyclooxygenase-2. Serum level of prostaglandin E(2) was also evaluated. All types of chemical peeling reduced tumor formation in treated mice, mostly in the treated area but also in the non-treated area. Peeling suppressed retention of p53-positive abnormal cells and reduced mRNA expression of cyclooxygenase-2 in treated skin. Further, serum prostaglandin E(2) level was decreased in chemical peeling treated mice. These results indicate that chemical peeling with glycolic acid, salicylic acid and trichloroacetic acid could serve tumor prevention by removing photo-damaged cells.
... Those characterized by antioxidant properties (i.e., LBA, GL) were superior to glycolic or lactic acid (Berardesca et al, 1997). Additionally, topical treatment with either glycolic and lactic acid appears to enhance UVB-and UVA-induced tanning (Tsai et al, 2000;Kaidbey et al, 2003), which does not seem to occur with GL (Green et al, 1999;Rona et al, 2004). SC acidification, however, can influence mechanisms taking place in the viable epidermis, at least at the SG level. ...
We have previously shown that the Na+/H+ antiporter (NHE1) is an essential endogenous pathway responsible for stratum corneum (SC) acidification. Since the epidermis must re-establish its epidermal barrier after acute barrier perturbations, we asked whether the NHE1 was, in turn, regulated by changes in barrier status. We found that in vivo epidermal NHE1 expression was upregulated within hours of barrier disruption. We next asked whether NHE1 was regulated by barrier status per se, or by the SC alkalinization that accompanies barrier perturbation. NHE1 was upregulated by alkalinizing SC pH, whereas this antiporter was downregulated by acidifying SC pH, independent of changes in barrier status. Moreover, acidifying SC pH overrode the effects of barrier break in regulating NHE1 expression, suggesting that SC alkalinization is the major stimulus for increased NHE1 expression. Finally, we confirmed that the keratinocyte NHE1 antiporter is regulated by extracellular pH independent of barrier status, by demonstrating that NHE1 was upregulated in cultured keratinocytes exposed to pH 8.3 medium and downregulated in cultured keratinocytes exposed to pH 6.3 medium. These data suggest that the keratinocyte NHE1 is regulated by extracellular pH. SC barrier break also upregulates NHE1 expression, but this response seems to be mediated by concomitant changes in SC pH.
... Toluidine blue-azure II. Scale bar: 50 mm (A, C, E), 100 mm (B, D, F). damaging effects of UV light (Kaidbey et al., 2003). This photosensitivity is reversed within a week of terminating treatment. ...
Use of alpha hydroxy acids (AHA) to ameliorate specific dermatological problems with keratinization has become fairly widespread. The aim of this study was to evaluate the effects of the AHA derivative of glycolic acid, applied in different dosages, on rat skin using light and electron microscopy. Skin biopsies were taken from the dorsal side of rats (n=16) and at the end of each week after applying solutions containing AHA: week 1, 8% (n=5); week 2, 50% (n=5); week 3, 70% (n=6). The skin samples were fixed in 10% formalin for histology and 2.5% glutaraldehyde solution for electron microscopy and processed using routine protocols. Histological sections were stained with hematoxylin and eosin (H&E), Masson's trichrome and were also labelled for binding of a primary antibody against collagen I using the avidin-biotin-peroxidase method. The epidermal thicknesses were measured and the fibroblast count of the dermis was taken and the results compared using the statistical ANOVA test. Semi-thin sections were stained with toluidine blue-azure II solution and ultrathin sections were contrasted with uranyl acetate and lead citrate. Histochemical and immunohistochemical observations demonstrated that AHA treatment resulted in statistically significant increased thickness of the epidermis and an increase in numbers of active fibroblasts and in the amount of dense collagen, especially at higher dosages of AHA. Ultrastructural examination of rat skin from AHA-treated groups showed cytoplasmic vacuolization in epidermal keratinocytes, intercellular dysjunctions, and increased quantities of organized bundles of collagen fibers in the dermis. The use of AHA in appropriate dosages has been found to play an important role in the treatment of specific skin disorders, however, the harmful effects of use of AHAs at higher concentrations should not be ignored. We conclude that alpha hydroxyl acids have a wide spectrum of use in the field of dermatology but, due to side-effects, their use, dosage, and time frame should be restricted to the advice of dermatologists.
Purpose:
We aimed to find active substances to help relieve the symptoms caused by increased photosensitivity after alpha hydroxy acid (AHA) peeling.
Methods:
A questionnaire survey was provided to 66 patients who received AHA peeling therapy to understand if increased photosensitivity existed and its specific symptoms. We verified increased photosensitivity after AHA peeling by monitoring cell viability to detect the combined toxicity of glycolic acid (GA) and UVB in HaCaT cells. The ELISA method was used to determine the expression of KLK7, FLG, IL-1β, and IL-8 to correlate damage to the skin barrier and inflammation induced by GA and UVB and the relieving effects of Portulaca oleracea extract.
Results:
Our survey results showed that 6.06% of people were more sensitive to sunlight after AHA peeling than before. Experiments at the cellular level showed that UVB induced cytotoxicity on HaCaT cells pre-treated with GA. Combined exposure of GA and UVB induced up-regulation of KLK7 and down-regulation of FLG and increased inflammatory cytokines of IL-1β and IL-8. P. oleracea extract inhibited the reduction of FLG and increased KLK7, IL-1β, and IL-8 expression caused by combined exposure.
Conclusions:
Our study found that combined exposure to GA and UV disrupted the skin barrier and induced significant inflammation. These results provided a theoretical basis for increased photosensitivity after chemical peeling. P. oleracea extract ameliorated GA and UVB-induced impaired skin barrier function and inflammation in HaCaT cells and may have the potential to relieve photosensitivity after AHA peeling.
The cosmeceutical market is a vast and rapidly growing global industry with hundreds of new products introduced each year. Patients often turn to cosmeceuticals to address their skin problems since these products are more accessible and affordable than prescription products. Unlike most drugs, cosmeceuticals do not undergo strict safety or efficacy testing by the FDA since they are classified as cosmetics. While the marketed properties of some ingredients are thoroughly researched and supported by clinical studies, not all ingredients have been tested to this standard, with some having only molecular or in vitro evidence and hardly any clinical authentication to support their use. Given these characteristics of the industry, dermatologists need to be familiar with cosmeceuticals in order to provide appropriate recommendations to their patients. The goal of this review was to explain the mechanism of action and evaluate the efficacy of popular cosmeceutical ingredients.
Background
Topical application of polyunsaturated fatty acids (PUFAs) has shown satisfactory results in dogs and humans with allergic skin diseases. Urea and glycolic acid act as keratolytics and moisturizers. Culicoides hypersensitivity is the most common equine hypersensitivity disorder and only limited treatment options exist.
Objectives
To evaluate the effect of a cream containing topical PUFAs, humectants and emollients on clinical signs of equine Culicoides hypersensitivity.
Animals
Privately owned horses (n = 28) with clinical signs of Culicoides hypersensitivity.
Methods and materials
For a period of four weeks, one half of the horse's body (left or right) was treated with a cream containing concentrated fish oil and several moisturizing and emollient ingredients in a randomized, single‐blinded fashion to evaluate the influence of the treatment on skin lesions. In the subsequent four weeks, the lesional areas of the entire body were treated to assess the treatment effect on pruritus. Additionally, the quality of the hair coat, an overall assessment and adverse effects were recorded.
Results
Twenty‐one horses completed the study. Skin lesions on the treated side improved significantly between days 0 and 28 (P < 0.0001) in comparison to the untreated side. Neither pruritus scores nor coat quality improved significantly between days 0 and 56. Overall condition improved during the study. Five horses showed adverse effects.
Conclusions and clinical importance
The cream improved Culicoides‐induced skin lesions in affected horses, but anti‐pruritic effects were less prominent.
Exposure to UVB radiation induces inflammation and free radical-mediated oxidative stress through reactive oxygen species (ROS) that play a crucial role in the induction of skin cancer. Glycolic acid (GA) is frequently used in cosmetics and dermatology. The aim of the study was to analyze the photoprotective mechanisms through which GA retards UVB-induced ROS accumulation and inflammation in normal human epidermal keratinocytes (NHEKs) and mice skin, respectively. NHEK cell line and C57BL/6J mice were treated with GA (0.1 or 5 mM) for 24 h followed by UVB irradiation. ROS accumulation, DNA damage, and expression of inflammasome complexes (NLRP3, NLRC4, ASC, and AIM2) were measured in vitro. Epidermal thickness and inflammasome complex proteins were analyzed in vivo. GA significantly prevented UVB-induced loss of skin cell viability, ROS formation, and DNA damage (single and double strands DNA break). GA suppressed the mRNA expression levels of NLRC4 and AIM2 among the inflammasome complexes. GA also blocked interleukin (IL)-1β by reducing the activity of caspase-1 in the NHEKs. Treatment with GA (2%) inhibited UVB-induced inflammation marker NLRC4 protein levels in mouse dorsal skin. The photoprotective activity of GA was ascribed to the inhibition of ROS formation and DNA damage, as well as a reduction in the activities of inflammasome complexes and IL-1β. We propose that GA has anti-inflammatory and photoprotective effects against UVB irradiation. GA is potentially beneficial to the protection of human skin from UV damage.
INTRODUCTION From time immemorial, people have tried to maintain healthy skin or to treat skin problems with such topical applications as mud, urine, animal products, oils, plants, or plant extracts and resins, and others. All of these were virtually ineffective except mud applications, which did have the advantage of providing UV protec- tion. Generally, cosmetics developed into applications of colored substances on the skin to disguise the problems beneath. Over time, simple creams came into use and with them a burgeoning industry that today makes a fortune selling creams, gels, and other topical products largely produced from inexpensive ingredients such as simple fats or oils and emulsifiers or gelling agents, with colors and added per- fumes to disguise the natural smell. The industry was built on selling “hope in a jar” because the most that these products could do was to create a surface barrier or oil that would inhibit the natural loss of water through the epidermis and thereby alleviate dry skin. Mesmerizing advertisements to promote the latest magical ingre- dient promising eternal youth and beautiful skin were the only effective ingredients in the whole package. There has never been a shortage of gullible buyers, and so the cosmetics industry eventually became an industry driven by seductive titles and fanciful packages containing ineffective serums or creams laden with inviting colors and perfumes.
INTRODUCTION Alpha hydroxy acids (AHAs) and retinol (free or palmitate ester) are frequently used ingredients in cosmetic products. These products are often advertised to reduce fine lines and wrinkles and to improve skin condition in general. Chemically, the two classes of ingredients are quite different. AHAs are generally smaller, more hydrophilic molecules, whereas retinol and its esters, such as retinyl palmitate, are much more lipophilic. Skin absorption studies of these chemicals have increased our understanding of the potential local and systemic exposure from topical use of products containing these ingredients. In addition, studies have been conducted to evaluate the effect of hydroxy acids on skin sensitivity to UV light.
Cosmetics are a category of consumer products that is sold worldwide. Many trade and regulatory agencies now refer to cosmetics as personal care products to try and better account for some of the diversity of these products; however not all personal care products marketed in the USA are regulated as cosmetics. For the 12-month period up to December 2008, the personal care products industry worldwide sales grew by 4% to 247 billion [1]. The use of some categories of personal care products to improve the appearance of aging is discussed here.
In western societies, a rapidly increasing number of people visit dermatologists for treatment and prevention of aging skin and the demand for cosmetic dermatology is growing. In between an arena of formulations that commercially promise reversal of aging, lie the few, so far proved to have an effect, topical treatments for aging skin. These include drugs and cosmeceuticals and are the focus of this review. Retinoids are the drugs histologically and clinically proven to reverse skin aging. Cosmeceuticals are available to consumers without prescription, yet these preparations can alter the structure and function of the skin. The hydroxy acids and topical vitamins fit into this category.
Moisturizer is such a commonplace term undoubtedly meaning many things to different people. So while the common feature of skin needing moisturization is a loss of the natural stratum corneum moisture content, the quantitative and qualitative extent will vary. According to Marie Lodén, moisturizers should be tailored with respect to the dermatological abnormality [1]. Defining the dermatological abnormality may help understand the consumer need, but acceptance by the end user, whether patient or cosmetic user, may be driven by other factors. Individuals with a xerosis arising from pathology - e.g. ichthyosis or eczema - may have similar needs to someone with senile xerosis, but the intensity, persistence and cosmetic properties of the treatment may vary, as may the appropriate ingredients. Likewise, there may be subtle differences between the needs of those who seek improvement in skin moisturization as a result of environmental challenges such as surfactant drying, short-term sun exposure and ageing. The concept of the dry-skin cycle has shifted thinking on the dermatological abnormality from a dry versus moisturised state to a dynamic model [2, 3]. This helps explain why moisturization remains the top unmet consumer skin needs, a constant point of reference in this chapter and further defined in Sect. 21.2. © 2012 Springer-Verlag GmbH Berlin Heidelberg. All rights are reserved.
The harmful effects of solar radiation on the organism originate mainly from Ultraviolet rays. Sun burn, an acute and visible reaction arising from skin exposure to such radiation, can cause serious coetaneous lesions, cellular des- truction and harmful effects on connective tissue, and may even be accompanied by oedema and loss of liquids. The aims of this work have been to describe and assess the effects of skin reactions to exposure to ultraviolet radiation, to elucidate on different prevention strategies and/or treatment of the sunburn. In general, it seems to be necessary to stress the importance of adopting healthy habits with regard to ultraviolet radiation exposure, especially important in fi rst eighteen y cars of live, and to carry out educational campaigns to prevent the appearance and/or worsening of conditions arising from such.
The harmful effects of solar radiation on the organism originate mainly from Ultraviolet rays. Sun burn, an acute and visible reaction arising from skin exposure to such radiation, can cause serious coetaneous lesions, cellular destruction and harmful effects on connective tissue, and may even be accompanied by oedema and loss of liquids. The aims of this work have been to describe and assess the effects of skin reactions to exposure to ultraviolet radiation, to elucidate on different prevention strategies and/or treatment of the sunburn. In general, it seems to be necessary to stress the importance of adopting healthy habits with regard to ultraviolet radiation exposure, especially important in first eighteen y cars of live, and to carry out educational campaigns to prevent the appearance and/or worsening of conditions arising from such.
A rapidly increasing number of people visit dermatologists for the prevention and treatment of aging skin. Sun avoidance and sunscreen use are widely accepted strategies of primary prevention against photoaging. Convincing evidence shows that topical application of retinoids has an effect on reversing, at least partially, mild to moderate photodamage. Antioxidants and α-hydroxy acids can alter the skin structure and function. Enzymes that repair DNA damage or oligonucleotides that enhance the endogenous capacity for DNA damage repair may prove to be future preventive/therapeutic interventions for aging skin.
For treating irregular skin pigmentation, a hallmark of premature skin aging, safe and effective alternatives to hydroquinone and kojic acid are being researched.
Four skin-brightening actives targeting melanin formation at multiple levels, namely disodium glycerophosphate, L-leucine, phenylethyl resorcinol, and undecylenoyl phenylalanine, in an oil-in-water emulsion cream were evaluated.
Twenty female patients with mild-to-moderate epidermal melasma were included. After a washout period of 1 month with a sunscreen, they continued using the sunscreen and added the novel skin-brightening cream for 12 weeks twice daily to entire face.
Whereas there was no significant change in skin pigmentation during the washout, signs for uneven skin tone including melasma area and severity and appearance of lentigines significantly decreased by up to 43% after the 12-week treatment period with the skin-brightening cream. The skin-brightening complex is well tolerated, which should allow its continued use over a prolonged period of time, in particular, when comparing skin-brightening approaches with exfoliating or peeling agents.
When used with a daily sunscreen, the skin-brightening complex represents a valuable alternative to hydroquinone products and can be used for maintenance or adjunct skin care with lightening therapies.
Chemical peeling is one of the dermatological treatments available for certain cutaneous diseases and conditions or improvement of cosmetic appearance of photoaged skin.
We assessed the photochemopreventive effect of several clinically used chemical peeling agents on the ultraviolet (UV)-irradiated skin of hairless mice.
Chemical peeling was done using 35% glycolic acid dissolved in distilled water, 30% salicylic acid in ethanol, 10% or 35% trichloroacetic acid (TCA) in distilled water at the right back of UV-irradiated hairless mice every 2 weeks in case of glycolic acid, salicylic acid, and 10% TCA and every 4 weeks in case of 35% TCA for totally 18 weeks after the establishment of photoaged mice by irradiation with UVA+B range light three times a week for 10 weeks at a total dose of 420 J/cm(2) at UVA and 9.6 J/cm(2) at UVB. Tumor formation was assessed every week. Skin specimens were taken from treated and non-treated area for evaluation under microscopy, evaluation of P53 expression, and mRNA expression of cyclooxygenase (COX)-2. Serum level of prostaglandin E(2) was also evaluated.
All types of chemical peeling reduced tumor formation in treated mice, mostly in the treated area but also non-treated area. Peeling suppressed clonal retention of p53 positive abnormal cells and reduced mRNA expression of COX-2 in treated skin. Further, serum prostaglandin E(2) level was decreased in chemical peeling treated mice.
These results indicate that chemical peeling with glycolic acid, salicylic acid, and TCA could serve tumor prevention by removing photodamaged cells.
Alpha-hydroxy acids (AHAs) have been widely used in cosmetic industry. However, knowledge on cytotoxicity of AHAs in human keratinocytes is limited.
Lactic acid (LA) is one of the most commonly used AHAs in skin care and peeling formulations. We investigated the antiproliferative effects of LA in a human keratinocyte cell line (HaCaT).
HaCaT cells were treated with LA at 7.5 approximately 17.5mM for various time periods. The molecular mechanisms of anti-proliferation through cell cycle arrest and apoptosis were investigated by 4,6-diamidino-2-phenylindole dihydrochloride (DAPI) stain, flow cytometry, Western blot and confocal microscopy.
Viability of HaCaT cells decreased on exposure to LA. Flow cytometry showed apoptosis was closely related to the increase of reactive oxygen species (ROS) and calcium release, and to the decline of mitochondrial membrane potential (MMP). Western blotting showed an increase in the levels of P21, P27 and a decrease in the levels of Cyclin E, Cyclin A, and CDK 2, indicating cell cycle arrest at G1/S. The occurrence of apoptosis was proved by the increased expressions of Fas, Bax, caspase-3, -8, and -9, apoptosis-inducing factor (AIF), and endonuclease G (EndoG), and the declined expressions of Bcl-2 and Bcl-xL. In addition, the intracytosolic release of AIF, EndoG, and cytochrome c contributing to the occurrence of apoptosis was demonstrated by confocal microscopy.
We demonstrated that LA had antiproliferative effect in HaCaT cell through the inhibition of cell cycle progression at G1/S, and the induction of programmed cell death through caspase-dependent and caspase-independent pathways.
Intense pulse light (IPL) treatment currently represents one of the most popular non-ablative photodamage skin treatments. Recent anecdotal evidence suggests that aminolevulonic acid (ALA) photodynamic therapy using IPL as a light source is superior to IPL alone for photorejuvenation.
Seven adult subjects (six women, one man) with minimal photodamage were treated with full face IPL treatment. Half of the face was pre-treated with topical ALA. Pre-and post-treatment biopsies were analyzed for changes in collagen by electron microscopic ultrastructural analysis.
An increase in type I collagen fibers was seen after treatment in all subjects. There was a greater increase in type I collagen formation in those subjects who were pre-treated with topical ALA.
This small pilot study is the first to focus on the ultrastructural changes seen after ALA-IPL photorejuvenation. We found a greater shift toward type I collagen synthesis in the ALA-IPL group compared to the IPL group. The addition of ALA to IPL treatment for photorejuvenation may be superior to IPL alone.
Unlabelled:
Aging is a complex, multifactorial process resulting in several functional and esthetic changes in the skin. These changes result from intrinsic as well as extrinsic processes, such as ultraviolet radiation. Recent advances in skin biology have increased our understanding of skin homeostasis and the aging process, as well as the mechanisms by which ultraviolet radiation contributes to photoaging and cutaneous disease. These advances in skin biology have led to the development of a diversity of treatments aimed at preventing aging and rejuvenating the skin. The focus of this review is the mechanism of photoaging and the pathophysiology underlying the treatments specifically designed for its prevention and treatment.
Learning objectives:
At the conclusion of this learning activity, participants should be familiar with the mechanism of photoaging, the treatments for photoaging, and the data that supports the use of these treatments.
The aim of this study was to develop hydrogel patch using crosslinked chitosan–starch as polymeric matrix for controlling the release of the natural alpha-hydroxy acid (AHA) contained in the extract of tamarind's fruit pulp. The chitosan (MW 100 000) was blended with corn, tapioca or rice starch in various ratios and then crosslinked with glutaraldehyde. The physical characteristics, mechanical resistance, bio-adhesion property and surface morphology of the prepared hydrogel patches with and without the extract were investigated. The release patterns of the hydrogel patches containing the extract were investigated by measuring the amount of tartaric acid, a major AHA present in the tamarind's fruit pulp extract, accumulated in the receptor medium of the vertical diffusion cell at various time intervals over a period of 6 h. The results indicated that the formulations of chitosan : corn starch 4.5 : 0.5 with glutaraldehyde 0.02% w/w (C4.5C0.5G0.02) or 0.04% w/w (C4.5C0.5G0.04), chitosan : tapioca starch 4.5 : 0.5 with glutaraldehyde 0.04% w/w (C4.5T0.5G0.04) or 0.05% w/w (C4.5T0.5G0.05), and chitosan : rice starch 4.5 : 0.5 with glutaraldehyde 0.04% w/w (C4.5R0.5G0.04) and chitosan : rice starch 4.0 : 1.0 with glutaraldehyde 0.03% w/w (C4.0R1.0G0.03) provided the flexible and elastic patches with good bio-adhesive property. The tensile strength values ranged from 5 to15 N mm−2 and the elasticity ranged from 30 to 60%. The addition of the extract in these formulations significantly increased the tensile strength values of the obtained patches. The patch of C4.0R1.0G0.03 formulation containing the extract showed relatively highest porosity, corresponding to its highest amount (12.02 ± 0.33 mg) and rate (0.452 ± 0.012 mg mm−2 min−1/2) of tartaric acid released. The amounts of tartaric acid released from the developed hydrogel patches were proportional to a square root of time (Higuchi's model), particularly the release from C4.0R1.0G0.03 (R2, 0.9978 ± 0.0020) and C4.5R0.5G0.04 (R2, 0.9961 ± 0.0024) patches.
Le but de cette étude était de développer un patch hydrogel en utilisant, en tant que matrice polymère, un mélange chitosane/amidon réticulé pour le contrôle du relargage d’α-hydroxyacide naturel contenu dans l'extrait de la pulpe du fruit du tamarinier. Du chitosane (MW 100 000) a été mélangéà des farines de maïs, de tapioca ou de riz dans différentes proportions, les mélanges ont été réticulés avec du glutaraldéhyde. Les caractéristiques physiques, résistance mécanique, propriétés de bio adhésion et morphologie de surface des patchs hydrogels préparés avec et sans extrait ont étéétudiées. Le profil de relargage des patchs hydrogels contenant l'extrait a étéétudié en mesurant la quantité d'acide tartarique, α-aminoacide majoritaire présent dans l'extrait, accumulé dans le milieu récepteur d'une cellule à diffusion verticale en fonction du temps sur une période de 6 heures. Les résultats ont montré que les formulations contenant:
• un mélange chitosane/amidon de maïs dans un rapport 4.5 : 0.5 réticulé avec 0.02% ou 0.04% poids/poids de glutaraldéhyde (respectivement C4.5C0.5G0.02 et C4.5 C0.5 G0.04) ou
• un mélange de chitosane/amidon de tapioca dans un rapport 4.5 : 0.5 réticulé avec 0.04% ou 0.05% poids/poids de glutaraldéhyde (C4.5T0.5 G0.04ou C4.5 T0.5 G0.05)
• ainsi que le mélange chitosane/amidon de riz dans un rapport 4.5 : 0.5 réticulé avec 0.04% poids/poids de glutaraldehyde (C4.5R0.5 G0.04)
• et le mélange chitosane/amidon de riz dans un rapport 4.0 : 1.0 réticulé avec 0,03% poids/poids de glutaraldehyde (C4.0 R1.0 G0.03)
conduisaient à des patchs flexibles et élastiques avec de bonnes propriétés bio adhésives. Leur résistance mécanique varie de 5 à 15 N/m2 et leur élasticité de 30 à 60%. L'addition de l'extrait de fruit à ces formules augmente significativement la résistance mécanique des patchs. Le patch C4.0R1.0 G0.03 contenant l'extrait montre la plus grande porosité correspondant à la quantité d'acide tartarique relargué la plus élevée (12.02 ± 0.33 mg), ainsi qu’à la plus grande vitesse de relargage (0.452 ± 0.012 mg mm-2 mn-1/2). Les quantités d'acide tartarique relarguées à partir de patchs hydrogels développés sont proportionnelles à la racine carrée du temps (modèle d'Higuchi), en particulier pour les patchs C4.0 R1.0G0.03 (R2, 0.9978 ± 0.0020) et C4.5R0.5 C0.004 (R2, 0.9061 ± 0.0024).
The efficacy of lactic acid-containing products is linked to their ability to deliver it to specific skin strata. The penetration of L+ lactic acid to different skin layers of porcine skin from various emulsions was measured in vitro using flow-through diffusion cells. The effects of pH, propylene glycol, product structure, and mode of application on percutaneous absorption of lactic acid were investigated. The absorption of lactic acid from oil-in-water (o/w) emulsions was measured at pH 3.8 and 7.0. The effect of propylene glycol (5%) as a penetration enhancer for lactic acid was also investigated from an o/w emulsion. The emulsion was applied either as a finite-dose 2-pl topical film or as a 75-pl "infinite"-dose occluded patch on a 0.64-cm 2 skin disc. A key finding was that the effects of changes in product compositions such as vehicle pH and propylene glycol on percutaneous absorption of lactic acid depended on the application mode. Increasing the aqueous phase acidity in an oil-in-water emulsion enhanced lactic acid delivery in the finite dose but not in the infinite-dose application. Finite-dose films were significantly more efficient than infinite dose for lactic acid delivery to tissue compartments. The penetration enhancer propylene glycol was more efficacious at the infinite-dose application. However, it also significantly enhanced lactic acid delivery to viable epidermis in the finite-dose application. Finally, the effect of emulsion phase structure on lactic acid uptake was investigated by comparing delivery from oil-in-water (o/w), water-in-oil (w/o), and water-in-oil-in- water (w/o/w) multiple emulsions with identical compositions. The total tissue delivery of lactic acid from the three emulsions was in the order of o/w > w/o/w > w/o.
Synopsis Alpha hydroxy acids (AHAs) are used in many cosmetic products as exfoliants, moisturizers, and emollients. The activity of AHAs on skin is likely influenced by their ability to be absorbed into the different layers of skin. The absorption of a homologous series of AHAs was measured through hunnan skin by using in vitro diffusion cell techniques. The (4C) radiolabeled compounds were applied to the skin in an oil-in-water emulsion vehicle. The absorption of the AHAs was measured at pH 3.0, to simulate the pH of the most acidic cosmetic formulations, and at pH 7.0, to observe the effect of complete ionization of AHAs on skin penetration. Much greater absorption of the AHAs was seen at pH 3.0. We also observed substantial absorption into the various skin layers (stratum corneum, viable epidermis and dermis) as well as the receptor fluid. Total absorption of glycolic acid and lactic acid was similar (27-30%). Absorption of the longer-chain AHAs decreased to 21.0% and 19.3%, for 2-hydroxyoctanoic and 2-hydroxydecanoic acids, respectively. At the end of the 24-h studies, these longer-chain AHAs did not form a depot in the skin. The stratum corneum was shown to have a pH gradient with an average pH near 7 at the viable epidermal layer. Therefore, the AHAs ionize to polar molecules as they enter and diffuse through the stratum corneum.
UV light is considered an important contributor to skin cancer, but methods have been lacking to quantify specific UV-induced lesions in human skin in situ. We applied a newly developed 32P-postlabeling technique to measure specific UV-induced cyclobutane dimers and 6-4 dipyrimidine lesions in the skin of healthy volunteers. At a dose of 400 J/m2, solar-simulated radiation caused at least 20 cyclobutane dimers/10(6) nucleotides, which is much higher than any known DNA adducts induced by specific external chemical exposure in human target tissues. This may explain why patients with DNA repair syndromes, such as xeroderma pigmentosum, preferentially develop skin cancer. We applied the 32P-postlabeling technique to study rates of DNA repair in healthy individuals. The obtained data indicated a base sequence dependence of the repair process. The applied method has potential for the study of DNA repair as a determinant of individual susceptibility to skin cancer.
An agarose plug method for isolating high-molecular-length DNA from mammalian tissues has been developed, including from those that are difficult, such as skin. It gives high yields of DNA that contain a minimum of single-strand breaks and is readily digested by restriction and other nucleases. The method requires only simple equipment and is readily adaptable to field or clinical studies.
Several commonly used emollients were studied as to their effectiveness in absorbing and filtering erythema-causing ultraviolet radiation in the 280 to 315 nm range (UVB). Planter's Peanut Oil (Standard Brands) and Mazola Corn Oil (Best Foods Inc) had no effect; Alpha Keri Bath Oil (Westwood Pharmaceuticals), mineral oil, and Johnson's Baby Oil (Johnson & Johnson Co) had minimal effects. Vaseline Petroleum Jelly (Chesebrough-Ponds Inc), petrolatum, and hydrophilic ointment substantially reduced the erythema that was induced by exposure to low doses of UVB radiation. Therefore, these emollients may interfere with the therapeutic effects of the ultraviolet radiation component of the Goeckerman treatment when it is administered in low doses to patients with psoriasis.
(Arch Dermatol 115:1188-1191, 1979)
This report provides a review of the safety of Glycolic Acid, Ammonium, Calcium, Potassium, and Sodium Glycolates, Methyl, Ethyl, Propyl, and Butyl Glycolates, Lactic Acid, Ammonium, Calcium, Potassium, Sodium, and TEA-Lactates, and Lauryl, Myristyl, and Cetyl Lactates. These ingredients belong to a group known as alpha-hydroxy acids (AHAs). Products containing these ingredients may be for consumer use, salon use, or medical use. This report does not address the medical use. In consumer and salon use, AHAs can function as mild exfoliants, but are also used as pH adjusters and skin-conditioning agents. AHAs are absorbed by the skin; the lower the pH, the greater the absorption. Metabolism and distribution studies show expected pathways and distribution. Consistent with these data, acute oral animal studies show oxalate-induced renal calculi, an increase in renal oxalate, and nephrotoxic effects. No systemic effects in animals were seen with dermal application, but irritation at the sight of application was produced. While many animal studies were performed to evaluate AHA-induced skin irritation, it was common for either the AHA concentration or the pH of the formulation to be omitted, limiting the usefulness of the data. Clinical testing using AHA formulations of known concentration and pH was done to address the issue of skin irritation as a function of concentration and pH. Skin irritation increased with AHA concentration at a given pH. Skin irritation increased when the pH of a given AHA concentration was lowered. Repeat insult patch tests using lotions and creams containing up to 10% Glycolic or Lactic Acid were negative. Glycolic Acid at concentrations up to 10% was not comedogenic and Lactic Acid at the same concentrations did not cause immediate urticarial reactions. Glycolic Acid was found to be nonirritating to minimally irritating in animal ocular tests, while Lactic Acid was found to be nonirritating to moderately irritating. In vitro testing to predict ocular irritation suggested Glycolic Acid would be a minimal to moderate-severe ocular irritant, and that Lactic Acid would be a minimal to moderate ocular irritant. Developmental and maternal toxicity were reported in rats dosed by gavage at the highest dose level used in a study that exposed the animals on days 7-21 of gestation. No developmental toxicity was reported at levels that were not maternally toxic. AHAs were almost uniformly negative in genotoxicity tests and were not carcinogenic in rabbits or rats. Clinical reports suggested that AHAs would enhance the penetration of hydroquinone and lidocaine. Animal and clinical tests were done to further evaluate the potential ofAHAs to enhance the skin penetration of other chemical agents. Pretreatment of guinea pig skin with Glycolic Acid did not affect the absorption of hydroquinone or musk xylol. Clinical tests results indicated no increase in penetration of hydrocortisone or glycerin with Glycolic Acid pretreatment. Because AHAs can act to remove a portion of the stratum corneum, concern was expressed about the potential that pretreatment with AHAs could increase skin damage produced by UV radiation. Clinical testing was done to determine the number of sunburn cells (cells damaged by UV radiation that show distinct morphologic changes) produced by 1 MED of UV radiation in skin pretreated with AHAs. A statistically significant increase in the number of sunburn cells was seen in skin pretreated with AHAs compared to controls. These increases, however, were less than those seen when the UV dose was increased from 1 MED to 1.56 MED. The increase in UV radiation damage associated with AHA pretreatment, therefore, was of such a magnitude that it is easily conceivable that aspects of product formulation could eliminate the effect. Based on the available information included in this report, the CIR Expert Panel concluded that Glycolic and Lactic Acid, their common salts and their simple esters, are safe for use in cosmetic products at concentrations ≤10%, at final formulation pH≥3.5, when formulated to avoid increasing sun sensitivity or when directions for use include the daily use of sun protection. These ingredients are safe for use in salon products at concentrations ≤30%, at final formulation pH ≥3.0, in products designed for brief, discontinuous use followed by thorough rinsing from the skin, when applied by trained professionals, and when application is accompanied by directions for the daily use of sun protection.
The influence of UVA and visible radiation on the acute damage by short-wave ultraviolet radiation (UVR) (λ < 320 nm) was investigated in human volunteers, using delayed erythema and sunburn cell production as markers of injury. It was found that subsequent exposure to UVA + visible radiation produced a significant reduction of the threshold erythema dose by short-wave UVR, in a dose-dependent manner. Subsequent exposures to varying doses of UVA + visible radiation, as well as to visible light alone failed to influence sunburn cell production. It is concluded that there is a positive interaction between short-wave UVR and UVA in the induction of delayed erythema, but this may not apply to epidermal cell injury. Photorecovery was not observed.
We assessed the in situ time-dependent loss of epidermal thymine dimers and 6-4 photoproducts in skin types I and H after exposure to two minimal erythema doses of solar-simulating radiation on previously unexposed buttock skin. Using quantitative image analysis, we evaluated biopsy sections stained with monoclonal antibodies. We then made comparisons, in the same volunteers, with unscheduled DNA synthesis, which is a direct marker of overall excision repair. Removal of thymine dimers was slow (half-life = 33.3 h), with high levels of lesions still present 24 h post-irradiation; some lesions were still present at 7 d. In contrast, removal of 6-4 photoproducts was rapid (half-life = 2.3 h), the decay kinetics of which correlated better with the decline in epidermal unscheduled DNA synthesis (half-life = 7.1 h). These data show that as in mouse, monkey, and in vitro models, the 6-4 photolesion is repaired preferentially in human epidermis in situ. They also raise the possibility that poor thymine dimer repair may be a feature of skin types I and II, who are more prone to skin cancer than are types III and IV. There was an inverse relationship between the onset of erythema and 6-4 photoproduct repair, suggesting that this repair process initiates erythema.Keywords: DNA photodamage, DNA photolesions, DNA repair
Several commonly used emollients were studied as to their effectiveness in absorbing and filtering erythema-causing ultraviolet radiation in the 280 to 315 nm range (UVB). Planter's Peanut Oil (Standard Brands) and Mazola Corn Oil (Best Foods Inc) had no effect; Alpha Keri Bath Oil (Westwood Pharmaceuticals), mineral oil, and Johnson's Baby Oil (Johnson & Johnson Co) had minimal effects. Vaseline Petroleum Jelly (Chesebrough-Ponds Inc), petrolatum, and hydrophilic ointment substantially reduced the erythema that was induced by exposure to low doses of UVB radiation. Therefore, these emollients may interfere with the therapeutic effects of the ultraviolet radiation component of the Goeckerman treatment when it is administered in low doses to patients with psoriasis.
Cyclobutyl pyrimidine dimers are major photoproducts formed upon irradiation of DNA with ultraviolet light. We have developed a method for detecting as few as one pyrimidine dimer per million bases in about 50 ng of non-radioactive DNA, and have used this method to quantitate dimer yields in human skin DNA exposed in situ to UV. We found that UVA radiation (320–400 nm) produces detectable levels of dimers in the DNA of human skin. We also measured UVB-induced dimer yields in skin of individuals of differing sun sensitivity and found higher yields in individuals with higher UVB minimal erythema doses and greater sun sensitivity. These approaches should provide important information on damage induced in human skin upon exposure to natural or artificial sources of ultraviolet radiation.
The influence of UVA and visible radiation on the acute damage by short-wave ultraviolet radiation (UVR) (lambda less than 320 nm) was investigated in human volunteers, using delayed erythema and sunburn cell production as markers of injury. It was found that subsequent exposure to UVA + visible radiation produced a significant reduction of the threshold erythema dose by short-wave UVR, in a dose-dependent manner. Subsequent exposures to varying doses of UVA + visible radiation, as well as to visible light alone failed to influence sunburn cell production. It is concluded that there is a positive interaction between short-wave UVR and UVA in the induction of delayed erythema, but this may not apply to epidermal cell injury. Photorecovery was not observed.
The inflammation produced by exposure to ultraviolet (UV) light has been well documented clinically and histologically. However, the mechanisms by which mediators induce this clinical response remain poorly defined. It is clear that photochemistry occurring after UV absorption must be responsible for initiating these events. Some of these underlying mechanisms have been defined. After exposure to UV light, the formation of prostaglandins and the release of histamine are increased. In addition to an increase in the quantity of these mediators, an increase in sensitivity of irradiated tissue to agonist stimulation also occurs. This increased sensitivity may cause tissue to respond to agonist levels previously present. Phospholipase activity also increases, making more substrate available for prostaglandin formation. Oxygen radical-induced peroxidation of membrane lipids caused by irradiation may contribute to increased phospholipase activity. Oxygen-free radicals also participate in sunburn cell formation and in UV-induced decreases in Langerhans cell numbers. Several enzymatic and non-enzymatic mechanisms are present in skin for reducing these highly reactive oxygen species.
Concerns about photosensitizing potential of alpha hydroxy acids have been expressed. A previous study, however, reported topical glycolic acid showing the opposite potential, that is, photoprotective. This study was designed to test the antiinflammatory and photoprotective capabilities of glycolic acid.
The effects of short-wave ultraviolet light (UVB) on skin treated with glycolic acid were evaluated in two different studies at two different locations.
In the first study the antiinflammatory potential of topical glycolic acid was tested on erythematous templates on the backs of human volunteers. Erythema was induced by exposure to three times the minimum erythema dose (MED) of UVB. Glycolic acid cream in an oil-in-water vehicle at 12% partially neutralized with ammonium hydroxide to a pH of 4.2 was applied to the template beginning 4 hours postirradiation four times a day. A second template on the same subject was used as a vehicle control. After 48 hours a marked reduction of erythema was noted when compared with the vehicle control site. In the second study, four test sites were exposed to UVB light in the following manner. Site 1 was a nontreated control site and was used to establish the MED for the subjects being tested; site 2 was also exposed to a MED series but was treated 24 hours postirradiation for 7 days with two glycolic acid-based products (cleanser and oil-free moisture lotion, both containing 8.0% glycolic acid at a pH of 3.25); site 3 was treated first with the two glycolic acid-based formulas for 3 weeks prior to being exposed to UVB light; and site 4 was treated as outlined in site 3, with the inclusion that the site was chemically peeled for 6 minutes (with a 50% glycolic solution at a pH of 2.75) 15 minutes prior to UVB exposure.
When UVB-burned skin was treated with glycolic acid daily for 7 days (site 2), a 16% reduction in irritation was observed compared to nontreated skin (site 1), implying that skin healed sooner when treated with glycolic acid. When a comparison of nontreated skin was made to skin treated with glycolic acid for 3 weeks prior to UVB exposure (site 1 vs site 3), a sun protection factor (SPF) of 2.4 was achieved. When a comparison of skin treated for 3 weeks was made to skin treated for 3 weeks and chemically peeled (site 3 vs site 4) the data implied that the chemical peel reduced the SPF value of skin treated with glycolic by approximately 50%, however, an SPF trend of 1.7 was still obtained when compared with untreated skin. CONCLUSIONS. The studies demonstrated that topical glycolic acid provides a photoprotective effect to pretreated skin yielding an SPF of approximately 2.4. In addition, when glycolic acid is applied to irradiated skin, it accelerates resolution of erythema. The data obtained from both studies support the hypothesis that glycolic acids acts as an antioxidant.
This article reviews advances in the study of the molecular mechanisms for ultraviolet (UV)-induced keratinocyte apoptosis, with particular reference to the cytokines tumor necrosis factor-alpha (TNF-alpha) and Fas ligand (FasL). TNF-alpha and FasL induce their respective receptors and then activate caspase enzymes that are critically involved in the apoptotic process. This activation is further amplified by intracellular mitochondria-associated mechanisms. Using gene-targeted knockout mice lacking either the TNF-Rp55 or the TNF-Rp75, we have shown that TNF-alpha plays an important role in UV-induced keratinocyte apoptosis via TNF-Rp55. TNF-Rp55 shares homology with Fas and contains an intracellular death domain. UV seems to directly stimulate cross-linking of Fas, resulting in the engagement of the death machinery. Fas-associated death domain protein (FADD) acts as an adapter protein in both the TNF-Rp55 and Fas death-inducing cascades and is responsible for downstream signal transduction by recruiting caspases. Moreover, signaling of p53 contributes to the induction of apoptosis by regulating Bcl-2 family expression and increasing surface Fas expression. In addition to induction mechanisms of apoptosis, there are numerous inhibitory molecules that play a role in restricting the apoptotic pathway. Thus, the ultimate determination of whether or not a cell undergoes apoptosis after UV radiation is based on the balance between agonist and antagonist pathways.
Topical use of alpha-hydroxy acid (AHA) may increase skin photosensitivity, as demonstrated by increased numbers of sunburst cells. However, effects of AHA on tanning have not been studied.
Our purpose was to study whether short-term use of glycolic acid hastens resolution of pre-existing light-induced pigmentation and whether the skin becomes tan more easily in Asian and Caucasian subjects after such treatment.
Six Asian and six Caucasian volunteers received separate irradiations of UVB and UVA to both sides of the lower back. In a double-blind fashion, patients then applied a 10% glycolic acid gel, pH 3.52, to one side of the back, including the irradiated area, and the contralateral extensor forearms once daily for 7 days and then twice daily for 2 weeks. A placebo gel, pH 5.75, was applied to the opposite sides. The subjects returned for measurement of residual tanning with a colorimeter and received additional irradiation to forearms and a second site on the back. Resulting pigmentation was measured immediately after irradiation, at 2 hours, and at 1 week.
Increased UVB-induced skin tanning occurred on the forearm and the lower back in both races in areas pretreated with glycolic acid. UVA also caused increased tanning, but only on the extensor forearms in Asian subjects. Treatment with glycolic acid for 3 weeks had no effect on pre-existing light-induced pigmentation.
Short-term topical treatment of glycolic acid caused an increase in UVB tanning as well as in UVA tanning in some subjects, even in the absence of overt irritation. The inclusion of UVB, and even UVA, sunscreen in AHA products may be warranted.
A linear correlation between erythema intensity and DNA damage upon exposure to UV has not been firmly established. Many of the deleterious effects of UV exposure do occur after exposure to suberythemal doses. After DNA damage, cells undergo DNA repair. It is commonly accepted that when the burden of damage is beyond the repair capacities, the cell undergoes programmed cell death or apoptosis. The aim of this study is to quantify the amount of UV-induced DNA damage (estimated via the measurement of DNA repair or unscheduled DNA synthesis or UDS) and cellular damage (estimated via the determination of the density of sunburn cells or SBC). If DNA damage and erythema are correlated, similar intensity of UDS and similar density of SBC should be found in volunteers irradiated with a UV dose equal to two minimal erythema doses (MED). Our results show that in 15 different individuals the same relative dose (2 MEDs) provokes UDS values, which vary within a factor of 4. An even larger variability affects SBC counts after the same relative dose. When DNA damage or SBC are plotted versus the absolute dose (i.e. the dose expressed in J/m(2)), there is a rough correlation (with several exceptions) between dose and extent of UDS and SBC counts. It seems possible to divide the volunteers into two subpopulations with different susceptibilities to UV damage. It is well known that UDS and SBC measurements are often affected by large experimental indeterminacy, yet, the analysis of our results makes it plausible to suggest that for the triggering of erythema, a common threshold value for DNA damage or for SBC count are not to be found. In conclusion, the erythema response seems to be loosely correlated with DNA damage. This suggests that the protection offered by the sunscreens against DNA damage, the molecular basis of UV-induced mutagenesis, might not be related to the sun protection factor (SPF) indicated on the label of sunscreens, which is evaluated using the erythema as an endpoint.
Effects of topically applied glycolic acid (GA) on the sensitivity of human skin to UVinduced damage
- Sutherland K Bm Kaidbey
- Bennett
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Kaidbey K, Sutherland BM, Bennett PV, et al. Effects of topically applied glycolic acid (GA) on the sensitivity of human skin to UVinduced damage. In: Holick MF, ed. Biological Effects of Light 2001. Proceedings of a Symposium, Boston, Massachusetts, June 16±18, 2001. Boston: Kluwer Academic Publishers, 2001: 129±137.
The influence of UVA and visible radiation on acute damage by short-wave UVR (l < 320) Pyrimidine dimer formation in human skin
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- Kligman
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Nonaka N, Kaidbey KH, Kligman AM. The influence of UVA and visible radiation on acute damage by short-wave UVR (l < 320). J Invest Dermatol 1983; 81: 524±527. 13. Freeman SE, Gange RW, Sutherland JC, Sutherland BM. Pyrimidine dimer formation in human skin. Photochem Photobiol 1987; 46: 207±212.
Molecular mechanism of ultra-violet-induced keratinocyte apoptosis
- Wang L B Zhuang
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Zhuang L, Wang B, Sauder DN. Molecular mechanism of ultra-violet-induced keratinocyte apoptosis. J Interferon Cytokine Res 2000; 20: 445±454.
AHA‐type products proliferate in 1993
- Jackson EM
Jackson EM. AHA-type products proliferate in 1993. Cosmet Dermatol 1993; 6: 22±26.
Announcement of nominated chemicals approved and under consideration for toxicological studies by the National Toxicology Program (NTP)-Request for comments
Announcement of nominated chemicals approved and under
consideration for toxicological studies by the National Toxicology
Program (NTP)-Request for comments. Federal Register 1997; 62:
19348.
Molecular mechanism of ultraviolet-induced keratinocyte apoptosis
- Zhuang