Article

Sunscreen enhancement of UV-induced reactive oxygen species in the skin

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Abstract

The number of UV-induced (20 mJ cm(-2)) reactive oxygen species (ROS) generated in nucleated epidermis is dependent upon the length of time the UV filter octocrylene, octylmethoxycinnamate, or benzophenone-3 remains on the skin surface. Two-photon fluorescence images acquired immediately after application of each formulation (2 mg cm(-2)) to the skin surface show that the number of ROS produced is dramatically reduced relative to the skin-UV filter control. After each UV filter remains on the skin surface for t=20 min, the number of ROS generated increases, although it remains below the number generated in the control. By t=60 min, the filters generate ROS above the control. The data show that when all three of the UV filters penetrate into the nucleated layers, the level of ROS increases above that produced naturally by epidermal chromophores under UV illumination.

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... Genotoxic, developmental and other stress related affects were reported for BP-3. Furthermore, BP-3 had been demonstrated to produce ROS in situ and in vitro, instigating antioxidant responses (Hanson et al., 2006). Under UV-radiation, BP-3 is transformed to an excited triplet state, and mutagenicity may involve the transfer of UV energy to DNA. ...
... Photolysis of EHMC results in ROS production (Allen and Gossett, 1996), and EHMC produces ROS in situ and in vivo (Hanson et al., 2006). Oxidative stress effects were found in 100% of cases (Fig. 3E); EHMC altered activity of antioxidant enzymes (GSH, CAT, GPX, SOD), and LPO in D. rerio (Nataraj et al., 2019;Zhou et al., 2019). ...
... Like other OUVFs, OCT can generate ROS during photolysis (Allen and Gossett, 1996;Hanson et al., 2006); however, only two studies investigated this MOA, both in C. riparius. No effects were observed for GST-gene related expression (Gonz alez and Martinez-Guitarte, 2018), or GST or CAT activity (Campos et al., 2017b), but heat shock protein (Hsp70) expression was affected in embryos, but not larvae (Oz aez et al., 2016b). ...
Article
Organic ultraviolet filters (OUVFs) are used in a wide range of manufactured products including personal care (e.g. sunscreens) and plastic items. This review summarizes the available data regarding the toxic effects of OUVFs on marine and freshwater organisms and generates the predicted no-effect concentration (PNEC) values necessary for assessing ecological risk. Through a systematic search of the literature, 89 studies were identified and ecotoxicological data extracted. Collectively, these studies described toxicity testing with 39 OUVF from 10 structural classes, with derivatives of benzophenones (49%) and camphors (16%) most studied. There was a bias towards selecting freshwater species (61%), and evaluating single OUVF effects (87%) rather than OUVF mixtures. Short-term (acute) experimentation (58%) was marginally more common than long-term (chronic) testing (42%). Reproductive, developmental, genetic, and neurological toxicity were the most commonly identified effects in aquatic organism, and were associated with molecular interactions with steroid receptors, DNA, or the production of reactive oxygen species. Species sensitivity distribution and/or assessment factors were used to calculate PNECs for 22 OUVFs and the risk quotients for 12 OUVFs. When using maximum concentrations, high risk was observed for six OUVFs in marine environments (4-methylbenzylidene-camphor, octocrylene, padimate-O, benzophenone-1, and oxybenzone, ethylhexyl-4-methoxycinnamate), and for four OUVFs in freshwater environments (ethylhexyl-4-methoxycinnamate, octocrylene, avobenzone and oxybenzone). When using median concentrations, a risk to marine environments was observed for oxybenzone. The results of this review underline that there is limited knowledge of the pathological effects of OUVFs and their metabolites in aquatic environments, and this inhibits the development of informed water-quality guidelines.
... Allen et al. (1996) found that OMC, OC, and aminobenzoic acid (PABA) produce 1 O 2 in phosphate-buffered saline after UV irradiation (Allen et al. 1996). Hanson et al. (2006) have shown that when OC, OMC, and BP-3 filters penetrate into nucleated cell layers, the level of ROS increases more than that produced naturally by epidermal chromophores after UV exposition (Hanson et al. 2006). The mechanism by which BP derivatives, OC, OMC, and other organic sunscreens generate ROS is not completely understood. ...
... Allen et al. (1996) found that OMC, OC, and aminobenzoic acid (PABA) produce 1 O 2 in phosphate-buffered saline after UV irradiation (Allen et al. 1996). Hanson et al. (2006) have shown that when OC, OMC, and BP-3 filters penetrate into nucleated cell layers, the level of ROS increases more than that produced naturally by epidermal chromophores after UV exposition (Hanson et al. 2006). The mechanism by which BP derivatives, OC, OMC, and other organic sunscreens generate ROS is not completely understood. ...
... The formed singlet oxygen can lead to the formation of O 2 -, followed by H 2 O 2 generation, which can interact with Fe 2þ , leading to OH through Fenton reaction (Gasparro 1997). This indicates that the UV filters are not able to completely protect cells from ROS, either directly formed by UV light when absorbed by skin chromophores, as indirectly by sunscreen UV photon absorption (Hanson et al. 2006). Other effects caused by sunscreen molecules, such as skin penetration, endocrine disruption, and environmental contamination are relevant regarding organic UV filters that should be mentioned. ...
Article
Although sunlight provides several benefits, ultraviolet (UV) radiation plays an important role in the development of various skin damages such as erythema, photoaging, and photocarcinogenesis. Despite cells having endogenous defense systems, damaged DNA may not be efficiently repaired at chronic exposure. In this sense, it is necessary to use artificial defense strategies such as sunscreen formulations. UV filters should scatter, reflect, or absorb solar UV radiation in order to prevent direct or indirect DNA lesions. However, the safety of UV filters is a matter of concern due to several controversies reported in literature, such as endocrine alterations, allergies, increased oxidative stress, phototoxic events, among others. Despite these controversies, the way in which sunscreens are tested is essential to ensure safety. Sunscreen regulation includes mandatory test for phototoxicity, but photogenotoxicity testing is not recommended as a part of the standard photosafety testing program. Although available photobiological tests are still the first approach to assess photosafety, they are limited. Some existing tests do not always provide reliable results, mainly due to limitations regarding the nature of the assessed phototoxic effect, cell UV sensitivity, and the irradiation protocols. These aspects bring queries regarding the safety of sunscreen wide use and suggest the demand for the development of robust and efficient in vitro screening tests to overcome the existing limitations. In this way, Saccharomyces cerevisiae has stood out as a promising model to fill the gaps in photobiology and to complete the mandatory tests enabling a more extensive and robust photosafety assessment. ARTICLE HISTORY
... Additionally, it is undesirable for a sunscreen to degrade into either reactive or toxic products. [6] These combined considerations mean that it is important to (i) determine the factors that affect photostability of individual sunscreen chromophores, and (ii) gain a broader fundamental understanding of the molecular level factors that affect photostability. [7] Octyl methoxycinnamate (OMC: alternatively known as ethylhexyl methoxycinnamate and octinoxate) is a common UV filter used in a variety of sunscreen products. ...
... photodynamics, [6,[10][11][12] and reactive oxygen sensitization, with quantum chemical studies also exploring details of the excited state characteristics. [13][14][15] Intriguingly, a wide variance in the reduction of OMC absorptivity has been reported in the various experimental studies, with absorbance being observed to vary greatly under different experimental conditions. ...
Preprint
Octyl methoxycinnamate (OMC) is a common UVA and UVB filter molecule that is widely used is commercial sunscreens. Here, we use gas-phase laser photodissociation spectroscopy to characterize the intrinsic photostability and photodegration products of OMC, by studying the system as its protonated form, i.e. [OMC·H]+. The major photofragments observed have, m/z 179, 161, and 133, corresponding to fragmentation on either side of the of the ether oxygen of the ester group (m/z 179, and 161) or the C-C bond adjacent to the ester carbonyl group. Additional measurements were obtained using higher-energy collisional dissociation mass spectrometry (HCD-MS), to identify fragments which result from breakdown of the vibrationally hot electronic ground state. We found that the m/z 179 and 161 ions are the main fragments produced by this route. Notably, the m/z 133 ion was not observed through HCD-MS, revealing that this product ion is only produced through a photochemical route. Our results demonstrate that UV photoexcitation of OMC is able to access a dissociative excited state surface that uniquely leads to rupture of the C-C bond adjacent to the key ester carbonyl group.
... In addition, octocrylene is very stable, and it may preserve and augment other UV absorbers while enhancing their skin coating uniformity [1]. Octocrylene may be easily absorbed into the skin and enhance reactive oxygen species [2]. However, as per the study of Matsuoka et al. (1990), sunscreens limit skin's ability to synthesise vitamin D3 by absorbing solar radiation. ...
... Octocrylene 50 mg Available online: https://www.amazon.de/Nivea-Feuchtigkeits-Sonnenlotion-2 00mL-Badartikel/dp/B000PE8B16 (Accessed 14 August 2022) 2 Bana Boat Sport performance Octocrylene 13.76 mg Available online: https://www.amazon.in/Banana-Boat-Performance-Sunscreen The United States Food and Drug Administration has approved octocrylene for the use of sun protection factor (SPF). ...
Article
Full-text available
Octocrylene is a widely used ingredient in sunscreen products, and it has been observed that the use of sunscreen has been increasing over the last few decades. In this paper, we investigated the way in which sunscreen’s ingredient octocrylene may disrupt normal vitamin D synthesis pathway, resulting in an imbalance in vitamin D levels in the body. The key techniques used for this insilico investigation were molecular docking, molecular dynamic (MD) simulation, and MMPBSA-based assessment. Vitamin D abnormalities have become very common in human health. Unknown exposure to chemicals may be one of the important risk factors. In molecular docking analysis, octocrylene exhibited a binding energy of −11.52 kcal/mol with vitamin D binding protein (1KXP) and −11.71 for the calcitriol native ligand. Octocrylene had a binding potency of −11.152 kcal/mol with the vitamin D receptor (1DB1), and calcitriol had a binding potency of −8.73 kcal/mol. In addition, octocrylene has shown binding energy of −8.96 kcal/mol with CYP2R1, and the calcitriol binding energy was −10.36 kcal/mol. Regarding stability, the root-mean-square deviation (RMSD), the root-mean-square fluctuation (RMSF), the radius of gyration, hydrogen bonding, and the solvent-accessible surface area (SASA) exhibited that octocrylene has a stable binding pattern similar to calcitriol. These findings revealed that incessant exposure to octocrylene may disrupt normal vitamin D synthesis.
... HA also has antioxidant properties and it is believed that it can protect against the effects of reactive oxygen species (ROS) [59]. Perhaps this explains the less harmful effect of BP-3 on this component of ECM, because one of the mechanisms of the action of this UV filter is the increase in the production of free radicals and ROS [60,61]. However, it is difficult to explain and relate these much smaller changes in the amount of total HA to significant changes in the expression of enzymes mRNA involved in the synthesis (HAS2) and degradation (HYAL2) of HA. ...
... The mechanisms of the harmful effects of UV radiation on human skin involve mainly the production of free radicals [1,2], hence the fear whether long-term use of BP-3 and other chemical filters may not protect, but intensify their formation [60,61]. It is known that ROS increase the expression of matrix metalloproteinases and serine proteases such as collagenase and elastase, thus contributing to the intensified degradation of ECM components of the skin manifested by the decrease in the skin's resistance to stretching, elasticity and firmness, as well as skin brittleness and wrinkles [2,58]. ...
Article
Full-text available
Benzophenone-3 (BP-3) is one of the most widely used chemical sunscreens. The results of many in vitro and in vivo tests confirm its high percutaneous penetration and systemic absorption, which question the safety of its wide use. The aim of our research was to assess the effect of this compound on components of the skin extracellular matrix, and to investigate whether rosmarinic acid (RA) could reduce BP-3-induced changes in human skin fibroblasts. BP-3 used at concentrations of 0.1–100 µM caused a number of unfavorable changes in the level of type I collagen, decorin, sulfated glycosaminoglycans, hyaluronic acid, elastin, and expression or activity of matrix metalloproteinases (MMP-1, MMP-2), elastase and hyaluronidase. Moreover, the intracellular retention of collagen was accompanied by changes in the expression of proteins modifying and controlling the synthesis and secretion of this protein. Most importantly, RA at a concentration of 100 µM significantly reduced or completely abolished the adverse effects of BP-3. Based on these findings, it can be concluded that this polyphenol may provide effective protection against BP-3-induced disturbances in skin cells, which may have important clinical implications.
... Although the mechanisms underlying oxybenzone toxicity to corals are still unclear, it may involve formation of tissue damaging reactive oxygen species (ROS) (Hanson et al., 2006;He et al., 2019). This mechanism seems similar to the effects elevated seawater temperatures and high light intensity (Dove et al., 2006). ...
Article
Full-text available
Coral bleaching due to global warming currently is the largest threat to coral reefs, which may be exacerbated by altered water quality. Elevated levels of the UV filter oxybenzone in coastal waters as a result of sunscreen use have recently been demonstrated. We studied the effect of chronic oxybenzone exposure and elevated water temperature on coral health. Microcolonies of Stylophora pistillata and Acropora tenuis were cultured in 20 flow-through aquaria, of which 10 were exposed to oxybenzone at a field-relevant concentration of ~0.06 μg L⁻¹ at 26 °C. After two weeks, half of the corals experienced a heat wave culminating at 33 °C. All S. pistillata colonies survived the heat wave, although heat reduced growth and zooxanthellae density, irrespective of oxybenzone. Acropora tenuis survival decreased to 0% at 32 °C, and oxybenzone accelerated mortality. Oxybenzone and heat significantly impacted photosynthetic yield in both species, causing a 5% and 22–33% decrease, respectively. In addition, combined oxybenzone and temperature stress altered the abundance of five bacterial families in the microbiome of S. pistillata. Our results suggest that oxybenzone adds insult to injury by further weakening corals in the face of global warming.
... Additionally, MPs can indirectly affect mitochondrial function by decreasing the mitochondrial membrane potential, leading to oxidative stress (Jeong et al., 2016). The generation of ROS caused by BP-3 has only been reported in human skin cells (Hanson et al., 2006), and the present study is the first to demonstrate ROS generation in D. magna under BP-3 exposure. In this study, co-exposure to MP fragments and BP-3 (MP + BP-3) at a lower concentration (0.10 mg L − 1 ) significantly (p < 0.05) increased ROS levels compared to the levels observed following individual exposure (Fig. 3a). ...
Article
The interactive effect of polyethylene microplastic (MP) fragments and benzophenone‐3 (BP-3) additives on Daphnia magna was assessed in the present study. The 48 h median effective concentration (EC50) revealed that MP fragments (37.24 ± 11.76 μm; 3.90 mg L⁻¹) were over 80 times more acutely toxic than polyethylene microbeads (37.05 ± 3.96 μm; 323 mg L⁻¹), possibly because of their irregular shape and high specific surface area. Moreover, the addition of BP-3 (10.27 ± 0.40 % w/w) to MP fragments (MP + BP-3) resulted in greater acute toxicity to D. magna (EC50 = 0.99 mg L⁻¹) compared to MP fragments (EC50 = 3.90 mg L⁻¹) or BP-3 (EC50 = 2.29 mg L⁻¹) alone. Additionally, MP + BP-3 exposure induced a synergistic increase in reactive oxygen species, total antioxidant capacity, and lipid peroxidation in D. magna. These synergistic effects can be attributed to enhanced bioconcentrations of BP-3 in D. magna caused by MP fragments. These findings suggest that MP fragments containing chemical additives represent a synergistic ecological risk and have the potential to harm aquatic organisms.
... 8 Due to their non-irritating and photo stable behavior, inorganic filters are gaining more attention from the researchers nowadays. Inorganic UV filters show opaque result on skin due to the high refractive index values which decreases their aesthetic charm 9 . The working principle of both types of sunscreens are explained through a systematic diagram ( Fig. 1) 10 . ...
Article
Full-text available
Background: Sunlight exposure causes several types of health issues to humans and in particular it affects especially the skin. Among the most common harmful issues developed by UV exposure are erythema, pigmentation and lesions in DNA, which may lead to cancer. These long-term effects can be minimized with the use of sunscreen. Objective: Use of commercial UV filters cause severe side effects like skin allergy and whitening of the skin etc. Therefore, in this study the effectiveness of Ca2 SiO4 , a compound abundantly present in the soils of certain South Asian regions, has been first time explored as UV filter. This compound leaves a low amount of white residue on the skin and is highly stable. Method: The comparative study of a cosmetic formulation having 5% Ca2 SiO4 , and other formulations containing 5% TiO2 and 5% ZnO as inorganic UV filters were performed to evaluate the physical and chemical stability. Result: The zeta potential and chemical stability of formulations containing these different UV filters were investigated by using UV-Vis spectroscopy, FTIR-ATR and X-ray diffraction. Results indicated Ca2 SiO4 as a promising innovative UV filter with an SPF value of 37.94. One of the reasons is its low interaction with organic filter i.e. PABA as compared to commercial ZnO and TiO2 inorganic UV filters. Biological absorption in organs was studied by ICP-MS on model mice. Conclusion: It also has a low photocatalytic activity; thus, formation of radicals is minimum. Moreover, Ca2 SiO4 showed a recognized ability to leave a low amount of white residue on the skin combined with great stability.
... Radiation of UVA (320−400 nm) and UVB (280−320 nm) from sunlight increases biological damage of skin, degradation of organic compounds, discoloration of dyes and pigments, weathering and yellowing of plastics and films, loss of mechanical properties (i.e., cracking) and other problems associated with UV irradiation [7,[16][17][18]. Manufacturers are interested in offering products that remain unaltered for long periods under severe sunlight exposure conditions [19,20]. ...
Article
Full-text available
Lignin is the by-product of pulp and paper industries and bio-refining operations. It is available as the leading natural phenolic biopolymer in the market. It has chromophore functional groups and can absorb a broad spectrum of UV light in range of 250–400 nm. Using lignin as a natural ingredient in sunscreen cream, transparent film, paints, varnishes and microorganism protection has been actively investigated. Both in non-modified and modified forms, lignin provides enhancing UV protection of commercial products with less than a 10% blend with other material. In mixtures with other synthetic UV blockers, lignin indicated synergic effects and increased final UV blocking potential in compare with using only synthetic UV blocker or lignin. However, using lignin as a UV blocker is also challenging due to its complex structure, polydispersity in molecular weight, brownish color and some impurities that require more research in order to make it an ideal bio-based UV blocker.
... After organic sunscreen compounds penetrate into the living epidermis, UV irradiation of these molecules may produce neoantigens, ultimately inducing a photoallergic contact dermatitis [88]. Additionally, several sunscreen compounds, though they protect against the formation of UV-signature CPDs, have been shown to paradoxically increase the rates of reactive oxygen species resulting in oxidative DNA damage, both in vitro and in vivo, after UV exposure [30,31,33,[89][90][91][92]. Some organic sunscreen compounds have also been reported to modulate estrogenic activity, though the clinical relevance of this remains unclear [93][94][95][96]. ...
Article
Ultraviolet radiation (UVR) exposure is well established as the major environmental risk factor for the development of melanoma, cutaneous squamous cell carcinoma (cSCC), and basal cell carcinoma (BCC). Additional risk factors including genetic mutations, other environmental agents, and immune status are important in modulating the effects of UVR. Dermatologists advocate a multi-pronged approach to minimizing UVR exposure including lifestyle modifications, UVR protective clothing, and topically applied sun-protective products, i.e. sunscreen. New Federal Drug Administration (FDA) regulations on sunscreen have brought certain long-standing ingredients in sunscreen products under scrutiny. The FDA's proposed rule for over the counter (OTC) monograph states that the inorganic sunscreens, zinc oxide and titanium dioxide, were found to be "generally recognized as safe and effective," but cite insufficient evidence to grant organic sunscreens the same designation. This proposed rule by the FDA and our increasing understanding of multifactorial mechanisms of UVR damage are an impetus for innovation and advances in sun protective technology. A complete set of strategies designed to limit the risk of UV-induced skin cell malignant transformation and tumor development must address the fuller consideration of genetic, environmental, and immune factors that cooperatively drive cutaneous carcinogenesis. Recent advances in our understanding of the biochemical processes underpinning UVR associated cutaneous cellular damage, genotoxicity, and clonal expansion provide investigators with a spectrum of opportunities for technologic innovation in the prevention of skin cancer. Strategies to improve upon current topical sunscreen formulations have strived for broader UVR spectral coverage, more favorable aesthetics, increased adherence, and minimal penetration into the living epidermis. In addition to improved sunscreens, future topical therapies may target processes within the epidermis that contribute to carcinogenesis. These include reactive species quenching, delivery of DNA repair enzymes, and targeting of cytokines essential to the proliferation of mutant keratinocytes.
... For instance, one may not get sunburned, but still have several unwanted effects occurring in the skin. The sunscreen actives oxybenzone, octocrylene, octinoxate, PABA, and the European 4-methylbenzyliden camphor have been reported to induce free radicals [6] known to cause caspase enzymes to be produced that are linked to adverse reactions like photosensitization [7], stimulation of melanoma tumor growth [8], and neurotoxicity [8][9][10][11][12] to name just a few. Therefore, it appears that the subversion of sunburn by sunscreen use is not free of the unseen consequences that can lead to the future development of skin cancers and toxicities. ...
Article
Full-text available
According to the Food and Drug Administration, the current scientific literature does not support the safety of organic sunscreen actives currently approved for use in the United States. Furthermore, the International Agency for Research on Cancer cannot find definitive proof that sunscreens prevent skin cancers. The concept that sunscreens prevent skin cancer is predicated on the observation that they inhibit the occurrence of sunburn and that one or two blistering sunburns can lead to skin cancer. Although the latter part of this statement may be true, the prevention statement is not and questions the efficaciousness of current sunscreen technologies in preventing melanoma and carcinomas period. We posit the thesis that current sunscreen technologies fail to protect against the threat of skin cancers when applied in common-occurrence situation(s). Therefore, before any local or global regulatory body approves old or new actives for human use, it is essential that 1) sunscreen actives demonstrate that they have the ability, alone or in combination, to sufficiently absorb/ block the entire ultraviolet spectrum, 2) validated models based on demonstrated toxicologic and exposure-delivery principles need to be developed to evaluate a product's efficacy to inhibit keratinocyte cancers or melanoma, and 3) safety testing as outlined in the Food and Drug Administration's Sunscreen Innovation Act of 2014 or similar tenets must be completed to assure human safety.
... Once in the water column, under UV radiation, O-UVFs can degrade well by direct or indirect photolysis through photoisomerization [11]. Some studies have shown that in aqueous solution and under UV radiation, UVFs can undergo photooxidation processes generating ROS which could produce damage to lipids, proteins, and DNA generating high levels of stress in marine organisms [14,[79][80][81][82][83][84] (Fig. 3). Therefore, this environmental compartment should be considered in any study that aims to address the distribution, accumulation, transformation, rates, mobilization, and bio-uptake of UVFs in marine waters. ...
Chapter
Since ancient times, humans have felt the need to protect their skin from the harmful effects of the sun: first with the use of vegetable oils or mud that were applied on the skin and then with the wearing of clothes, hats, or umbrellas. Today, the use of sunscreens around the world has become widespread. It has been shown that the use of these cosmetics can release large quantities of chemicals into coastal waters, either directly through bathing or indirectly through waste water treatment plants and atmospheric depositions. Due to the nature of the active ingredients of sunscreens, organic and inorganic UV filters, it has been proven that they can bioaccumulate and bioconcentrate in sediments and biota and can enter the food chain, being a problem whose true magnitude is still unknown.
... (43). A report by Hanson et al. (44) in 2006 revealed that OC was able to produce ROS in living human epidermis cell layers following UVR exposure. Given its structure, it was found using two-photon fluorescence microscopy that OC is also able to generate ROS in the cytoplasm of human epidermis nucleated keratinocytes after exposure to UVR. (43) BP-3 is known to exhibit a vast array of toxicological effects and has the highest incidence rate of photoallergic contact dermatitis. ...
Article
Full-text available
UV radiation is one of the critical environmental stress factors for human skin, which can trigger various problems such as pruritus, burning, erythema, premature skin aging, and skin cancer. Hence, UV‐protection has become an indispensable daily routine and the use of topical sunscreen products is rapidly increasing. However, there are emerging concerns over the efficiency and safety of existing chemical and physical UV filters used in consumer products. Furthermore, there is no universally approved method for assessing sun protection efficiency regardless of the immediate end user need to develop safer sunscreen products that afford broad‐spectrum photoprotection. It is evident that the current organic and inorganic UV filters have significant unfavorable impacts on human, environmental, and marine safety. Therefore, effective alternative UV filters should be established. This review article comprehensively describes the properties, safety, health, and ecological concerns of various UV filters including TiO2 and ZnO nanoparticles as well as the limitations of the testing protocols and guidelines provided by major regulatory bodies. The photoreactivity of UV filters used in sunscreen remains a major challenge and it is crucial to develop new sunscreen ingredients, which not only protect the consumer, but also the environment.
... These photoproducts, including cyclodimers, have different levels of cellular toxicity and may even be more toxic than OMC itself (Duale et al. 2010;Stein et al. 2017). They can sensitize singlet oxygen ( 1 O 2 ) and lead to ROS formation, but this mechanism needs to be explored (Hanson et al. 2006;Hanson et al. 2015). Some toxicological and genotoxic studies reported that OMC-induced genotoxic effects for both isomers seems to be different (Necasova et al. 2017;Sharma et al. 2017). ...
Article
Full-text available
Background Sunlight is one of the main harmful exogenous factors that induce the reactive oxygen species formation. The human skin is the first line of photoprotection against harmful exogenous factors, such as UV radiations. The topical application of sunscreens, containing UV-B filters, is widely used to protect against UV-induced damage. Octylmethoxycinnamate is the world’s most widely used UV-B filter in sunscreens. However, recent studies have demonstrated that this substance is an endocrine disruptor compound and with potential to damage DNA. Thus, the safety of this organic filter is a current concern for human health, and it was urgent to develop new photoprotective strategies. In this sense, due to the potential to neutralize the UV-induced free radicals, the use of antioxidants as UV filter stabilizers presented as a novel promising strategy. Research The purpose of this review was to assess the use of antioxidants as stabilizers for UV-B filter octylmethoxycinnamate. For this, we discuss the chemical and physical characteristics of UV-B filter octylmethoxycinnamate, emphasizing the stability, photostability, and reactivity of this UV filter. The use of antioxidants in sunscreens will also be addressed, from a perspective of the main characteristics that allowed their use in sunscreen formulations. Then, the concomitant use of both was described from a historical and physical chemical perspective, always emphasizing the advantages and disadvantages of this association. Conclusions The combination of antioxidants with UV-B filter octylmethoxycinnamate in appropriated formulations represents a viable strategy to protect the human skin against UV-induced damage.
... Although the mechanisms underlying oxybenzone toxicity to corals are still unclear, it may involve formation of tissue damaging reactive oxygen species (ROS) (Hanson et al., 2006;He et al., 2019). This mechanism seems similar to the effects elevated seawater temperatures and high light intensity (Dove et al., 2006). ...
Preprint
Full-text available
We studied the effect of chronic oxybenzone exposure and elevated temperature on coral health. Microcolonies of Stylophora pistillata and Acropora tenuis were cultured in 20 flow-through aquaria, of which 10 were exposed to oxybenzone at a field-relevant concentration of ~0.06 μg L ⁻¹ at 26 °C. After two weeks, half of the corals experienced a heat wave culminating at 33 °C. All S. pistillata colonies survived the heat wave, although heat reduced growth and zooxanthellae density, irrespective of oxybenzone. A. tenuis survival was reduced to 0% at 32 °C, and oxybenzone accelerated mortality. Oxybenzone and heat significantly reduced photosynthetic yield in both species, causing a 5% and 22−33% decrease, respectively. In addition, combined oxybenzone and temperature stress altered the abundance of five bacterial families in the microbiome of S. pistillata . Our results suggest that oxybenzone adds insult to injury by further weakening corals in the face of global warming. Highlights ➢ Chronic effect study on corals combining oxybenzone and elevated temperature ➢ Oxybenzone affected photosystem II of coral photosymbionts and altered coral microbiome ➢ Temperature effects were stronger than oxybenzone effects ➢ Sensitivities were species-dependent ➢ Oxybenzone adds insult to injury by weakening corals in the face of global warming
... However, increasing side effects of some sunscreen components has made it indispensable to search for natural photoprotectants. 2 The most commonly utilizing sunscreen ingredients such as oxybenzone linked to sun exposure triggered allergic reactions, generating free radicals, which may be associated with cell damages. 3,4 While the nanoscale TiO 2 and ZnO are responsible for the generation of a substantial amount of reactive oxygen species, which upon UV illumination causes modifications in nucleic acid bases and eventually cell death. 5,6 Consequently, it is the need of an hour to look for other options to replace harmful components of sunscreens. ...
Article
Full-text available
Red and yellow pigments from Monascus purpureus (NMCC-PF01) were evaluated to enhance sun protection factor (SPF) of commercial sunscreens and Aloe vera extract. The extracted Monascus pigments contain rubropunctamine (red pigment) and the mixture of monascin and ankaflavin (yellow pigment) as major components. Antioxidant activity and in-vitro safety of the pigments were assessed by ferric reduction potential and DPPH radical scavenging assays, human keratinocytes (HaCaT), and erythrocytes (RBCs) cytotoxicity assay, respectively. In results, SPF of commercial sunscreens showed an increase of 36.5% with red pigment compared to the 13% increase by yellow pigment. The in-vitro studies showed 67.6% ferric reducing potential and 27% DPPH radical scavenging activity, neither cytotoxic effect against human keratinocytes nor haemolytic activity. These results confirmed the safe nature of the Monascus pigments; however, in-vivo studies merit further research. In conclusion, screened pigments from Monascus purpureus may act as potential candidates to increase SPF of commercial sunscreen naturally.
... Thus, it can be concluded that, in GG-NER deficiency, mutations accumulate in areas of the skin exposed to UV radiation and prompt skin tumorigenesis 117 . By contrast, in most cases, TC-NER serves merely as an auxiliary mechanism against the cytotoxicity of DNA lesions 118 . Edema and erythema, rather than skin cancer, tend to be induced by UV when TC-NER is not intact. ...
Article
Full-text available
The genome of cells is constantly challenged by DNA damages from endogenous metabolism and environmental agents. These damages could potentially lead to genomic instability and thus to tumorigenesis. To cope with the threats, cells have evolved an intricate network, namely DNA damage response (DDR) system that senses and deals with the lesions of DNA. Although the DDR operates by relatively uniform principles, different tissues give rise to distinct types of DNA damages combined with high diversity of microenvironments across tissues. In this review, we discuss recent findings on specific DNA damage among different tissues as well as the main DNA repair way in corresponding microenvironments, highlighting tissue specificity of DDR and tumorigenesis. We hope the current review will provide further insights into molecular process of tumorigenesis and generate new strategies for cancer treatment.
... Zinc oxide (ZnO) and titanium dioxide micro-particles are the most popular inorganic UV reflecting sunscreen ingredients (TiO2) (Suh et al., 2019). Despite having a lower dermal penetration than organic particles, it has been demonstrated that they can nevertheless cause cellular damage and carcinogenesis by increasing the formation of reactive oxygen species after UV exposure (Griffith, 2022;Hanson et al., 2006;Rass & Reichrath, 2008). Benzophenones, This preprint research paper has not been peer reviewed. ...
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The major goal of this work is to formulate and characterize beeswax sunscreen. Five beeswax sunscreens were formulated and characterized according to international standards and protocols such as FDA, IUPAC, COLIPA, and APCC. For all samples, their absorbance, photochemical stability, and physical appearance were tested and measured. In general, the samples have a paleyellowish-white color. Beeswax and zinc oxide are the two main components that have an impact on samples' color. As a result, samples become more yellow or white as beeswax and zinc oxide concentrations rise, respectively. The samples have a paste-like sticky texture and an appealing aroma that resembles the essential oil ingredient's smell. The sun protection factor (SPF) of samples 1 and 2 is lower, and that of samples 4 and 5 is higher. Sample 3 has a sun protection factor between these two extremes. Sample 4 showed a lower water resistance value and maximum protection from (ultraviolet) UVA and UVB. Sample 5 showed higher SPF and good water-resistance properties. However, it exhibits a stickier texture and higher viscosity at room temperature. This impacts how evenly sunscreen covers the skin, which in turn affects how well it protects the skin from UV. Compared to samples 4 and 5, sample 3 exhibits average properties. It exhibits optimal SPF values that are higher than the labeled standard; strong water resistance; and good chemical and photo stability. Thus, sample 3 was chosen as the optimum formulation of beeswax sunscreen with an optimal percentage of 25% zinc oxide and 8.8% beeswax.
... In their study of photoallergic contact dermatitis in 82 patients, Rodriguez and coworkers [132] observed that more than 25% of the patients displayed photoallergic reactions to oxybenzone, while the study of Bryden et al. [133] reported that 20% of those examined in photo-patch tests displayed allergic reactions on exposure to oxybenzone. Besides being able to penetrate the skin, oxybenzone also causes skin damage as it forms free radicals on exposure to UV sunlight [111,134,135]. Oxybenzone also aids other chemicals such as the herbicide 2,4-dichlorophenoxyacetic acid to penetrate the skin [136]. ...
Article
Sunscreens have now been around for decades to mitigate the Sun’s damaging ultraviolet (UV) radiation which, although essential for the existence of life, is a recognized prime carcinogen. Accordingly, have suncreams achieved their intended purposes towards protection against sunburns, skin photo-ageing and the like? Most importantly, however, have they provided the expected protection against skin cancers that current sunscreen products claim to do? In the last two decades, there have been tens, if not hundreds of studies on sunscreens with respect to skin protection against UVB (280‒320 nm)—traditionally sunscreens with rather low sun protection factors (SPF) were intended to protect against this type of radiation—and UVA (320‒400 nm) radiation; a distinction between SPF and UVA protection factor (UVA-PF) is made. Many of the studies of the last two decades have focused on protection against the more skin-penetrating UVA radiation. This non-exhaustive article reviews some of the important facets of what is currently known about sunscreens with regard (i) to the physical UV filters titanium dioxide (TiO2) and zinc oxide (ZnO) and the mostly photo-unstable chemical UVB/UVA filters (e.g., octinoxate (OMC) and avobenzone (AVO), among others), (ii) to novel chemical sunscreen agents, (iii) to means that minimize the breakdown of chemical filters and improve their stability when exposed to UV sunlight, (iv) to SPF factors, and (v) to a short discussion on non-melanoma skin cancers and melanoma. Importantly, throughout the article we allude to the safety aspects of sunscreens and at the end ask the question: do active ingredients in sunscreen products pose a risk to human health, and what else can be done to enhance protection?Graphic abstractSignificant loss of skin protection from two well-known commercial suncreams when exposed to simulated UV sunlight. Cream I: titanium dioxide, ethylhexyl triazone, avobenzone, and octinoxate; Cream II: octyl salicylate, oxybenzone, avobenzone, and octinoxate.
... Moreover, inorganic UVFs enter aquatic organisms and induce ROS generation in vivo, which causes toxicological impacts on Chlorella spp. [144]. The production of ROS, either in vitro or in vivo, directly or indirectly, causes oxidative stress. ...
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An increasing number of inorganic ultraviolet filters (UVFs), such as nanosized zinc oxide (nZnO) and titanium dioxide (nTiO2), are formulated in sunscreens because of their broad UV spectrum sunlight protection and because they limit skin damage. However, sunscreen-derived inorganic UVFs are considered to be emerging contaminants; in particular, nZnO and nTiO2 UVFs have been shown to undergo absorption and bioaccumulation, release metal ions, and generate reactive oxygen species, which cause negative effects on aquatic organisms. We comprehensively reviewed the current study status of the environmental sources, occurrences, behaviors, and impacts of sunscreen-derived inorganic UVFs in aquatic environments. We find that the associated primary nanoparticle characteristics and coating materials significantly affect the environmental behavior and fate of inorganic UVFs. The consequential ecotoxicological risks and underlying mechanisms are discussed at the individual and trophic transfer levels. Due to their persistence and bioaccumulation, more attention and efforts should be redirected to investigating the sources, fate, and trophic transfer of inorganic UVFs in ecosystems.
... The range of UVR bands that reach the earth include UVB (290-320 nm) and UVA (320-400 nm) (Diffey et al. 2000). The most active and dangerous to the skin is UVB, but since only 4-5% of it reaches the earth, the skin is more likely to be intensely exposed to UVA (Afaq et al. 2002;Hanson et al. 2006). Normally, 90% of all the UVR that reaches the earth is UVA, which is far deadlier due to increased dermal inflammatory cells and diminished activity of epidermal antigens and epidermal Langerhans' cells (Svobodová et al. 2003;Sambandan and Ratner 2011;Saewan and Jimtaisong 2015). ...
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Phlorotannins are polyphenolic compounds in brown algae and can be used as a natural UV filter in sunscreen formulations. The aim of the present study was to characterize the biological activities of phlorotannins-rich fractions from the brown alga Polycladia myrica and to validate the protective effect as well as stability of cream formulation with phlorotannins against UVR. With respect to antioxidant properties, the ethyl acetate fraction (EF) possessed the highest DPPH radical scavenging (65 ± 0.2%), and the highest antioxidant activity (11.2 ± 0.2 μg ASA mg⁻¹). The EF was active against Gram-positive bacteria with EF effectively reducing UVB-induced cytotoxicity in HaCaT keratinocytes. The cream formulation with 5% EF revealed a high sun protective factor (31.79 ± 4.73), UVA/PF (24.67 ± 4.03), critical wavelength (383.2 ± 0.1 nm), and UVA/UVB ratio (0.98 ± 0.01). The cream formulation was completely homogeneous and had a pH close to human skin pH. The cream was stable in the cooling-heating cycle and the DPPH scavenging activity of the cream was not altered for 30 days of storage at temperatures of 4–40 °C. These findings are promising for the use of brown alga P. myrica extract as a valuable source of sunscreen protective substance for pharmaceutical and cosmetic applications.
... Despite the fact that sun light is necessary to generate vitamin D for the body, prolonged sun light UV exposure can cause significant damage to eyes and skin [1]. Based on the wave length, UV radiation is classified into three main categories; UV-A, UV-B and UV-C. ...
... However, most of the time these synthetic absorbers may have negative effects on human health and the environment. Indeed, (1) UV absorption may activate organic filters that consequently interact with cutaneous molecules, cause dermatitis or photosensitivity reactions (Dromgoole and Maibach, 1990), exhibit neurotoxic effects (Ruszkiewicz et al., 2017), pro-carcinogenic activities (Kerdivel et al., 2013), and generate ROS which are potential mutagens when applied topically to the UV-exposed skin (Hanson et al., 2006). Consequently, the terms 'endocrine disruptor' and 'allergenic substance' appeared a few years ago for most of the synthetic sunscreens (Schlumpf et al., 2001;Singh et al., 2011;Birkhäuser, 2016). ...
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Sunscreen oil-in-water emulsions containing few ingredients and two EU-authorized organic filters had been developed in an eco-friendly approach. Based on their photostability, spectroscopic features, and the lack of data on toxicity, BEMT (UVA/B range; bis-ethylhexyloxyphenol methoxyphenyl triazine) and DHHB (UVA; diethylamino hydroxybenzoylhexyl benzoate) were selected and incorporated at minimal concentrations to reduce the risk of impact on human health and coastal marine ecosystems. Despite the inconclusive results previously reported, the use of the w-soluble and largely available Na-lignosulfonate (LiS) had been reconsidered with success. Since BEMT and DHHB alone or in combination were not able to higher the sun protection factor (SPF) value at 50, results showed that it becomes possible by supplementing with LiS at 5% (w/w), ensuring stability, antiradical property, and a non-toxicity of the sun emulsion. After defining the range doses for the three components, minimizing concentrations was achieved by experimental design studies using a response surface methodology in which SPF values before and after irradiation has been considered. Consequently, an SPF30 and SPF50 emulsions containing only 9 and 12% total filter respectively and 5% LiS each had been developed. This high boosting effect led to discussions on how LiS interacts, suggesting the involvement of J aggregation, the formation of LiS micelles that would partly encapsulate the o-soluble filters, and the mode of adsorption at the solid-liquid interface of the poly(methyl-methacrylate) plate or the skin.
... The generation of ROS from exogenous agents is well established, environmental factors such as pollution, [107] ultra violet [108] and ionizing radiation, [109] smoking, [110] and Insecticides [111] are important sources of ROS and free radicals in organisms, which subsequently lead to serious health complications. ...
... Skin erythema can occur as a result of prolonged exposure to UVB (280-320 nm) rays. While exposure to UVA (320-400 nm) has a cumulative effect that ultimately producing photo-aging and/or skin cancer [1,2]. ...
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Annona squamosa is a medicinal plant that has been used in folk medicine since antiquity. The goal of this study is to see how effective Annona squamosa leaf extract (A.S.L.E) or its niosomal-entrapped preparation is at protecting skin from UVA irradiation. The prepared niosomal-entrapped A.S.L.E has been characterized via spectrophotometry and transmission electron microscopy imaging. Furthermore, the entrapment efficiency and in vitro release of A.S.L.E were determined. In this study, ex vivo and freshly prepared samples from the dorsal region of the rats’ skin were used as biological samples, which were divided into five groups: control UVA-unexposed, unprotected UVA-exposed, A.S.L.E-protected UVA-exposed, and niosomal-entrapped A.S.L.E UVA-exposed. UVA irradiation was performed by exposing the skin samples to a UVA-producing lamp for 4 h. Samples from various groups were then examined using FTIR spectroscopy, histopathology, and protein electrophoresis methods. The results showed that A.S.L.E has a skin protective effect against UVA irradiation. The niosomal-entrapped A.S.L.E was more effective than the native plant leaf extract in protecting skin from the damaging effects of UVA. Therefore, the nanotechnologically formulated preparation, niosomal-entrapped A.S.L.E, can be used as an effective photoprotector (sunscreen) against the adverse effects of UVA radiation. Graphical abstract
... Generation of 1 O 2 , O 2 − and • OH radical are being reported in sunscreens and hair dye phototoxicity [31,42]. Cosmetic ingredients in sunscreens induce UV-mediated oxidative stress in skin cells [43]. Earlier studies have reported that some of the hair dye constituents are potential nephrotoxic agents and cause severe nephrotoxicity in humans [44]. ...
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Cosmetics, commonly known as ‘makeup’ are products that can enhance the appearance of the human body. Cosmetic products include hair dyes, shampoos, skincare, sunscreens, kajal, and other makeup products. Cosmetics are generally applied throughout the face and over the neck region. Sunlight has different wavelengths of light, which include UV-A, UV-B, UV-C, and other radiations. Most cosmetic products have absorption maxima (λmax) in the range of visible light and UV-R. The effect of light-induced photosensitization of cosmetic products, which results in the production of free radicals through type-I and type-II photosensitization mechanisms. Free-radicals-mediated DNA damage and oxidative stress are common consequences of cosmetic phototoxicity. Cosmetic phototoxicity may include percutaneous absorption, skin irritation, eye irritation, photosensitization, mutagenicity, and genotoxicity. Oxidative stress induces membrane lipid peroxidation, glycoxidation, and protein covalent modifications, resulting in their dysfunction. Natural antioxidants inhibit oxidative-stress-induced cosmetic toxicity. Sunlight-induced photodegradation and accumulation of cosmetic photoproducts are also a matter of serious concern. India has tropical weather conditions throughout the year and generally, a majority of human activities such as commerce, agriculture, sports, etc. are performed under bright sunlight conditions. Thus, more focused and dedicated research is warranted to explore the effects of cosmetics on oxidative stress, glycoxidation of biomolecules, and photoproducts accumulation for its total human safety.
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In the present study, we explored the adverse effects of Octyl methoxycinnamate (OMC), and its photoproducts, namely 2-ethylhexanol (2-EH) and 4-methoxybenzaldehyde (4-MBA) on the developmental stages of zebrafish using various biomarkers such as developmental toxicity, oxidative stress, antioxidant response, neurotoxicity and histopathological changes. The effective concentrations (EC50) of OMC, 2-EH and 4-MBA were found to be 64.0, 34.0 and 3.5 μg/ml, respectively in the embryo toxicity tests. Embryos exposed to the EC50 of OMC, 2-EH and 4-MBA showed time-dependent increases in the malformation, heart rate and hatching delay. The lipid peroxidation (LPO) level was significantly (p < 0.05) increased and both induction and inhibition of SOD, CAT, GPx and GST activities were observed in the zebrafish larvae exposed to OMC, 2-EH and 4-MBA. GSH activity was significantly (p < 0.05) decreased in the highest exposure groups, for all the exposed compounds when compared with the control. AChE activity was increased in lower concentrations of OMC, 2-EH and 4-MBA exposed embryos whereas, the activity was found to be decreased in highest concentration. Moreover, the histopathological studies showed severe damage to the muscle fibers and yolk sac regions of the larvae with 4-MBA treatment. The photoproducts 4-MBA has the highest toxic effect, following by 2-EH and OMC. Our results provide useful insights into the impacts of OMC and its photoproducts on zebrafish development.
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Photochemical instability and reactivity of organic ultraviolet (UV) filters not only degrade the performance of sunscreen formulations but also generate toxic photodegradation products and reactive oxygen species (ROS). Although the encapsulation of organic UV filters into synthetic polymer particles has been widely investigated, synthetic plastics were recently banned for personal care and cosmetic products due to marine and coastal pollution issues. Here we present a plastic-free, photochemically stable and inactive UV filter platform based on chitosan-coated mesoporous silica microparticles, denoted ‘mSOCPs’, incorporating octyl methoxycinnamate (OMC) as a sunscreen agent. Sunlight induced the degradation of ~80% free OMC in artificial sweat in 1 h at room temperature, while only 20% of OMC degraded for 3 h when encapsulated within mSOCPs. Moreover, mSOCPs efficiently suppressed the photochemical generation of ROS by about 99% through the combined effects of the mesoporous silica structure and chitosan coating. Accordingly, mSOCPs substantially increased the cell viability of fibroblasts exposed to UV irradiation. This work demonstrates that the biopolymer coatings of mesoporous inorganic particles can be a promising approach to the plastic-free encapsulation of organic UV filters for suppressing their photochemical reactivity and degradation.
Chapter
Solar ultraviolet (UV) photons are established environmental carcinogens. Sunscreens (small molecule organic filters that absorb solar UV-photons and particle-sized inorganic filters that reflect and scatter UV-photons) are important topical solar photoprotectants and cancer chemopreventive molecular agents. Based on the emerging consensus that broad-spectrum photoprotection is an effective key component of a sun-safe strategy to reduce lifetime exposure to detrimental cumulative doses of solar UV light, much effort has been directed towards the identification, development, and optimization of photoprotectants that prevent and attenuate solar skin damage, a topic of particular relevance to high-risk patients such as immunosuppressed organ transplant recipients and individuals suffering from conditions associated with extreme photosensitivity. Generally, sunscreen development has aimed at (a) increased absorbance with broadened spectral coverage over the whole UVA/B spectrum, (b) optimized photostability of UV-active chromophores, and (c) prolonged skin residence time with minimal skin penetration and lack of off-target activity and systemic availability upon topical application. Extensive research has focused on the identification of targeted molecular interventions and agents that are expected to synergize with sunscreens and may also provide photoprotective benefit if used in stand-alone topical regimens (referred to as “non-sunscreen photoprotection”) through anti-inflammatory and antioxidant mechanisms. Importantly, recent legislation that responds to ecotoxicological concerns associated with sunscreen use that damages marine environments emphasizes an urgent need for the continuous development of more efficacious and safer molecular and nonmolecular strategies for skin photoprotection.
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Sunscreens (SSs) are highly applied all over the world on large areas of human body. Benzophenone chemical group constitute a major part in most SSs. Benzophenones are reported to induce changes in nucleic acids upon UV-irradiation. These alterations may potentially lead to DNA mutation, cell apoptosis, and eventually skin cancer. This work compares the kinetics of the induced DNA damage by some SSs after UV-irradiation. Six commonly used SSs; 4-t-butyl -4-methoxy dibenzoyl methane, 4-methoxy cinnamic acid, 2-hydroxy-4-methoxybenzophenone (BZ-3), Dibenzoyl methane, 2,2′- dihydroxy-4- methoxy benzophenone (BZ-8) and p-methylbenzoic acid; are investigated. In this work, terbium chloride bioluminescent genosensor is used for sensitive, simple and inexpensive determination of induced DNA-damage. Results reveal that only BZ-3 and BZ-8 induced DNA-damage upon UV-irradiation that are confirmed by both absorption spectroscopy and viscosity measurements. Moreover, viscosity studies indicated the possible intercalation of the SS into DNA prior to initiation of DNA damage. Furthermore, the potency of BZ-3 and BZ-8 to induce DNA damage upon UVA irradiation was assessed on calf thymus DNA. The low cost of the proposed bioluminescent genosensor allows it to be an automatic simple process for the investigation of any DNA-drug interactions without the need of coupling with other analytical methods.
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Ultraviolet (UV) filter is the core component of sunscreen and protects skin from various photo damages. Current UV filters are hampered by skin penetration, poor photo-stability, photocatalytic generation of harmful reactive oxygen species (ROS), and potential environmental risks. In this work, manganese dioxide nanoclusters were developed as an eco-friendly UV filter by a facile two-step synthesis, using colloid silica as support under ambient condition. These nanoclusters show better UV-shielding profile than commercial titanium dioxide nanoparticles and capability to scavenge various ROS. They can be easily incorporated by a sunscreen formula, and demonstrate excellent skin photo-protection performance both in vitro and in vivo.
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Although several short-term assays are available for cosmetic photosafety assessment, cell models are usually highly sensitive to UV radiation, tending to overestimate both phototoxic and photomutagenic risks. In addition, these assays are performed with UV doses/fluences that do not correspond to actual environmental conditions. In this sense, Saccharomyces cerevisiae has already proved to be an interesting tool to predict photomutagenic potential of several compounds, including sunscreens. Yeast can support environmental UVB doses compatible with human daily sunlight exposure, allowing the use of irradiation sources to faithfully mimic the external conditions of ambient sunlight. Herein, we used a set of S. cerevisiae mutant strains sensitive to UVA, UVB and Solar Simulated Light sources in order to evaluate their potential as bioindicators for sunscreen development. The bioindicator potential of the strains was tested with the widely-used titanium dioxide inorganic sunscreen. The AWP001 (yno1) and LPW002 (ogg1yno1) strains obtained in this study stood out as promising experimental tools for the validation of this assay. Overall, our results evidenced a set of S. cerevisiae strains particularly useful for evaluating both photoprotective (efficacy) and photo/antiphotomutagenic (safety) potential of UV filters, meeting the industries and regulatory agencies demand for robust and efficient in vitro screening tests.
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Taro mucilage, a hydrocolloid present in the rhizome of Colocasia esculenta (L.) Schott, was extracted and characterized by infrared spectroscopy, X-ray diffraction, scanning electron microscopy, thermal analysis, and proximal composition. In addition, cosmetic formulations based on extracted mucilage were developed and studied. The mucilage presented a semicrystalline structure with high thermal stability, the presence of granules along its surface area, and good emulsifying activity. High physical-chemical stability was also found in the mucilage and the cosmetic formulations during storage. All cream samples presented pseudoplastic behavior, with a flow behavior index lower than 1, which is a desirable characteristic for cosmetics, as it improves its applicability. The mucilage demonstrates potential for application in cosmetic products, and its commercial use as an ingredient in cosmetics could be a strategic tool for the creation of a new product chain and adding value to the culture of Colocasia0 esculenta.
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Organic and inorganic ultraviolet (UV) filters possess itself advantages, respectively, while suffer from different limitations including photostability, penetration and cytotoxicity. Integrating organic and inorganic UV filters in single unit holds great potential for enhanced UV protection. Herein, the dendritic silicon dioxide microspheres (DSM) are encapsulated with Bi2Ti2O7 nanocomposites (BTO-DSM), an inorganic filter, and decorated with organic filters including sinapoyl malate (SM) and baicalin (BS/BTO-DSM) to enhance UV protection while significantly reducing ROS and skin permeability under UV exposure. The inorganic BTO-DSM component presents expanded UV shield range and suppressed photocatalytic properties while preventing the organic filters SM direct contact with the epidermis and penetration behaviors. The baicalin efficiently scavenges the ROS generated from SM and reduce the transmittance of blue light. Notably, the results show that the proposed combined system significantly broaden the UV absorption region. Thus, the BS/BTO-DSM presents advanced in vitro anti-UV performance and in vivo UV protection against keratinocyte apoptosis and epidermal hyperplasia without long-term toxicity. The excellent anti-UV properties coupling with the suppressed photocatalytic capability and minimal epidermal penetration of BS/BTO-DSM make it promise in skin protection.
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In the case of a suspicious mole on the skin, the question always arises as to whether it is benign or malignant. Is it a harmless mole, a capillary malformation or a basal cell carcinoma, squamous cell carcinoma or even a melanoma? Often the nevus can be assessed just by a close examination of the lesion and a few questions about its origin. However, every dermatologist knows all too well the problem that very different lesions can look extremely similar to the naked eye and even on dermatoscopy. Therefore, the question arises: how should dermatology deal with and communicate in such cases? This article identifies ways forward in this difficult situation, which occurs tens of thousands of times a day around the globe.
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Background The interest in ultraviolet (UV) radiation from the sun and artificial sources has been recently increasing due to its toxic effects, including sunburn, erythema, photodamage, and photocarcinogenesis. In this study, we aimed to develop a valuable nanomaterial that can block total UV rays using an undervalued, yet profitable marine organism. We successfully developed carbon nanodots (CNDs) and a CNDs-polyvinyl alcohol (PVA) composite film that effectively protect against UV-A, UV-B, and UV-C radiation based on a common brown algae, sea cauliflower (Leathesia difformis), through simple hydrothermal synthesis in aqueous solution. Results CNDs-PVA film protected rhodamine B from photobleaching and polydiacetylene vesicles with 10,12-tricosadiynoic acid from polymerization. As-fabricated CNDs in aqueous solution blocked >99% of UV-A light, which causes photoaging and skin cancer. The CNDs-PVA film showed excellent transparency, with >84% transmittance of visible light, and effectively blocked >60% of UV-A/B and >30% of UV-C rays under direct and strong irradiation. Conclusions This preliminary work indicates that CNDs based on underutilized marine brown algae have strong potential for application in technologies for wide UV protection.
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The discovery of environmentally friendly and inexpensive plant growth regulators (PGRs) for agronomically important crops is a necessity and must be considered a priority worldwide. This study provides the synthesis, structure determination and the biological evaluation of two binary organic salts as potential PGRs. New compounds have dual biological activity and are based on natural metabolite p-aminobenzoic acid (pABAH) and different alkanolamines. Studied compounds exhibit hydrogen-bonded 3D supramolecular architectures with different crystal packing due to the formation of one homosynthon and various heterosynthons. The biological profile of new compounds was investigated in laboratory and greenhouse on Solanum lycopersicum L., revealing the efficiency in promoting plant rooting and plant productivity. The results may have a positive impact on agricultural economics, developing new sustainable PGRs for tomatoes.
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Melanin is considered a bio-inspired dermo-cosmetic component due to its high UV absorption and antioxidant activity. Among various melanin sources, fungal melanin is a promising candidate for sunscreen because of its sustainability and scalability; however, quantitative assessment of its function has not yet been sufficiently explored. In this study, melanin samples derived fromAmorphotheca resinaewere prepared, followed by the evaluation of their sunscreen performance, antioxidant activity, and cytotoxicity. Melanin-blended cream was prepared by blending a melanin suspension and a pure cream. The cream showed anin vitrosun protection factor value of 2.5 when the pigment content was 5%. The cream showed a critical wavelength of approximately 388 nm and a UVA/UVB ratio of more than 0.81, satisfying the broad-spectrum sunscreen requirement. Oxygen radical absorbance capacity assays indicated that fungal melanin had antioxidant activity similar to ascorbic acid but higher than reduced glutathione. Fungal melanin had no statistically significant cytotoxicity to human keratinocyte cell lines until 72 h of exposure, even at a concentration of 4 mg mL⁻¹. Consequently, melanin pigment can be used as a biocompatible broad-spectrum sunscreen with high antioxidant activity and as a practical alternative in dermo-cosmetic formulations.
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Background: Although chemical sunscreens have traditionally been at the forefront of sun protection, safety concerns and increasing awareness of the environmental impact of personal-care products have led to greater interest in the use of mineral blockers as photoprotective agents. Objective: To examine the safety and efficacy of mineral-based sunscreens to allow patients to make informed choices about ultraviolet (UV) protection. Materials and methods: A review of the literature was performed using the PubMed database. Results: This article provides an overview of physical blockers and focuses on the efficacy of mineral sunscreens in offering broad-spectrum UV protection and safety concerns, including the controversy surrounding the use of nanoparticles. Practical tips for application are also reviewed. Conclusion: Mineral sunscreens are an attractive, efficacious option for consumers who prefer alternative choices in sun protection.
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4-tert-Butyl-4'-methoxydibenzoylmethane (BMDM) is widely used throughout the world as a highly effective UVA absorber that can prevent the progression of photoaging in skin. However, due to its low photostability, BMDM is also known for the disadvantage of having a reduced capability to absorb UVA during prolonged exposure to sunlight. Although many studies have been carried out to overcome this disadvantage of BMDM, little attention has been paid to how the radicals generated from BMDM during UV exposure influence the skin. Therefore, the purpose of this study was twofold: One goal was to clarify the influence of radicals on human skin using cytotoxicity as a parameter. The second was to propose a solution that could reduce the radical formation while taking photostability into consideration. Using ESR spin trapping and superoxide dismutase (SOD) treatment, the radicals produced by the UV exposure of BMDM were shown to be superoxide anion radicals (•O2–). HaCaT keratinocytes exposed to UVA in the presence of BMDM showed a significant reduction in cell viability, indicating that the radicals produced from BMDM have a harmful influence on the skin. UVA exposure coincidently led to a reduction of UVA absorbance by BMDM. Interestingly, 2-hydroxy-4-methoxybenzophenone (Benzophenone-3; BP3) reduced both the radical formation and the cytotoxicity resulting from the UVA-exposure of BMDM, while also restoring its UVA absorbance. In conclusion, the results show that BMDM and BP3 is an effective combination to reduce the influence of UVA-exposed BMDM on the skin and to prevent the loss of UVA absorbance by BMDM during UV exposure.
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Use of agri-biomass is a promising sustainable approach for the generation of functional materials. Such approach allows the generation of useful materials while utilizing agro-biomass at the same time. In this respect, lignin derivable from agri-biomass is an economic source to generate functional biomaterials with the biocompatibility and sustainability. As such, lignin has been favorably utilized as a raw material for the preparation of various substances including metal oxide nanocomposites (MONCs). In light of the potential utility of MONCs in numerous industrial products (e.g., coatings, paints, and cosmetics), the lignin-derived MONCs also show versatile applicability in many fields [e.g., Ultraviolet (UV) protection, photocatalysis, and antimicrobial agents] due to their beneficial properties such as biocompatibility, economical production, and low toxicity. Fabrication of an environment friendly and economically viable synthetic procedure employing lignocellulosic biomass as a raw material should be a plausible option for the development of UV protective material from the industrial perspective. This review aims to highlight the notable research findings (e.g., in viewpoint of lignin as an economically and environmentally better alternative to the raw chemical material for MONCs synthesis) made over the past few years. In this respect, our emphasis was placed on the development of lignin-based ZnO and TiO2 composites for UV protective applications. The use of lignin for the synthesis of MONCs is thus found as a significant technological advancement over the existing chemical-based methods. This review will also aid in expanding the future applications of lignin-based MONCs, especially with an emphasis on UV-protecting agents in diverse product forms (e.g., coatings, films, and sunscreen) with great marketing potential.
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The effects of ultraviolet (UV) radiation trigger human skin reaction, which can result in erythema, photoaging, and/or skin cancer. Sunscreens play an important role against the negative effects of UV radiation on the human skin. However, they should satisfy certain criteria, with the main one being photostability, to avoid the formation of health-threatening reactive intermediates. It has to be kept in mind, however, that photo-stable UV fi lters have the undesirable propensity to transfer energy to molecular oxygen and generate the very reactive singlet oxygen. They should also be well tolerated, while at the same time, they should not permeate into the skin and cause toxic effects. Thus, there is an ongoing need to develop effective and safe non-penetrating sunscreen formulations. The search for innovative active substances, effi cacious combinations, and the design of vehicles or carriers has led to the implementation of advanced delivery systems. This study intended to review the commonly used UV radiation thwarting agents (organic and inorganic UV fi lters), compile the relevant toxicity studies, evaluate their margin of safety, and assess the current situation on innovative sunscreen formulations.
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Alzheimer's disease (AD) is a neurodegenerative disorder characterized by dementia, memory impairment, cognitive dysfunction, and speech impairment. The utility of cholinergic replacement by acetylcholinesterase (AChE) inhibitors in AD treatment has been well documented so far. Recently, studies have also evidenced that human carbonic anhydrases (hCAs) serve as an important target for AD treatment. In this direction, the improvement of new multitarget drugs, which can simultaneously modulate several mechanisms or targets included in the AD pathway, may be a potent strategy to treat AD. In light of these data for understanding and developing AD‐related multitarget AChE and hCAs inhibitors, in this study, novel methylene‐aminobenzoic acid and tetrahydroisoquinolynyl‐benzoic acid derivatives (4a–g and 6a–g) were designed. The synthesized analogs were experimentally validated for their effects by in vitro and direct enzymatic tests. Also, the compounds were subjected to in silico monitoring with Schrödinger Suite software to assign binding affinities of potential derivatives based on Glide XP scoring, molecular mechanics‐generalized Born surface area computing, and validation by molecular docking. The results revealed that 6c (1,3‐dimethyldihydropyrimidine‐2,4‐(1H,3H)‐dione‐substituted, KI value of 33.00 ± 0.29 nM), 6e (cyclohexanone‐substituted, KI value of 18.78 ± 0.09 nM), and 6f (2,2‐dimethyl‐1,3‐dioxan‐4‐one‐substituted, KI value of 13.62 ± 0.21 nM) from the benzoic acid derivatives in this series were the most promising derivatives, as they exhibited a good multifunctional inhibition at all experimental levels and in the in silico validation against hCA I, hCA II, and AChE, respectively, for the treatment of AD.
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Green, biocompatible, and biodegradable antioxidants represent a milestone in cosmetic and cosmeceutical applications. Lignin is the most abundant polyphenol in nature, recovered as a low-cost waste from the pulp and paper industry and biorefinery. This polymer is characterized by beneficial physical and chemical properties which are improved at the nanoscale level due to the emergence of antioxidant and UV shielding activities. Here we review the use of lignin nanoparticles in cosmetic and cosmeceutical applications, focusing on sunscreen and antiaging formulations. Advances in the technology for the preparation of lignin nanoparticles are described highlighting structure activity relationships.
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Reactive oxygen species (ROS) are generated and consumed in living organism for normal metabolism. Paradoxically, the overproduction and/or mismanagement of ROS have been involved in pathogenesis and progression of various human diseases. Here, we reported a two-dimensional (2D) vanadium carbide (V2C) MXene nanoenzyme (MXenzyme) that can mimic up to six naturally-occurring enzymes, including superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), glutathione peroxidase (GPx), thiol peroxidase (TPx) and haloperoxidase (HPO). Based on these enzyme-mimicking properties, the constructed 2D V2C MXenzyme not only possesses high biocompatibility but also exhibits robust in vitro cytoprotection against oxidative stress. Importantly, 2D V2C MXenzyme rebuilds the redox homeostasis without perturbing the endogenous antioxidant status and relieves ROS-induced damage with benign in vivo therapeutic effects, as demonstrated in both inflammation and neurodegeneration animal models. These findings open an avenue to enable the use of MXenzyme as a remedial nanoplatform to treat ROS-mediated inflammatory and neurodegenerative diseases. Materials with enzymatic-like activities are of interest for a wide range of applications. Here, the authors report on 2D vanadium carbide MXene nanozymes capable of mimicking multiple enzymes and demonstrate application to treat reactive oxygen species-mediated inflammatory and neurodegenerative diseases.
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Lignin-protected TiO2 can reduce the release of free radicals photogenerated by TiO2. This can be achieved through the intrinsic absorption of lignin that acts as an antioxidant strategically located on the surface of TiO2 particles while retaining – and to some degree improving – the light absorbing and scattering properties of TiO2. A 1-3% loading of lignin is sufficient to achieve this protection, with the coating produced photochemically taking advantage of the intrinsic free radical photogeneration capacity of TiO2. The process has been scaled up to amounts around 50 g per day by developing a large (10-25 liters) flow photoreactor. As industry tends to use larger particles, our studies show that radical generation is lower with 100 nm, compared with 25 nm TiO2 particles; further, rutile is less reactive than anatase, a desirable characteristic in the fields of sunscreen, cosmetic and health applications.
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In this study, we used the improved extreme-difference normalization method to calculate the comprehensive evaluation values of bioenrichment and toxicity of benzophenone UV light absorbers(BPs). Based on this parameter, a 3D-QSAR(QSAR=quantitative structure activity relationship) pharmacophore model was constructed using Discovery Studio software and applied to the molecular modification of BPs. With three commonly used ingredients in sunscreen 2-hydroxy-4-methoxybenzophenone(BP-3), 2,2′-dihydroxy-4,4′-dimethoxybenzophenone(BP-6) and 2,2′-dihydroxy-4-methoxybenzophenone(BP-8) as target molecules, we performed BPs substitution reaction based on the binding positions of characteristic elements of the pharmacophore model and designed BP derivatives with reduced bioenrichment and toxicity. Stability and function evaluation showed that while the stability of 6 BP derivatives was enhanced, the light absorption capacity was also significantly enhanced(from 9.16% to 43.16%). Molecular dynamics simulation results showed that the binding ability of BP-609 molecule with serum albumin was reduced by 16.37% compared with BP-6, and the binding with collagen could not occur spontaneously, which could be used as an explanation for the simultaneous reduction of its bioenrichment and toxicity. Besides, through the simulation of human metabolism, it was found that the liver metabolites of BP-609 were less toxic, which reduced the potential risk of human metabolism. It proved that the molecular modification scheme of BPs was environment-friendly.
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Malignant neoplasms of the skin are among the most common types of cancer worldwide. These include malignant melanoma and neoplasms of epithelial origin such as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). In recent decades, the incidence of these diseases has been steadily rising, making skin cancer increasingly important at the population level. The main reason for this increase in the incidence rate is the increasing exposure of the skin to UV radiation caused by changes in leisure time behavior, the use of solariums and the thinning of the ozone layer. This development must be counteracted by primary and secondary prevention strategies in order to reduce morbidity and mortality (especially for malignant melanoma) in the long term.
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The quantum yields for the photosensitized formation of singlet oxygen in air-saturated solutions of rhodamine 123 and its mono-, di-, and tetrabromo derivatives in water and ethanol were measured. The solubility of the dyes in these media and the spectral and luminescence characteristics of the solutions were studied. It was shown that, of mono-, di-, and tetrabromo-rhodamines, tetrabromorhodamine 123 is most efficient in generating singlet oxygen. The bromination results in a decrease in the solubility and small (2-3 nm per bromine atom) bathochromic shifts of the absorption and fluorescence spectra.
Chapter
Two-photon fluorescence microscopy is used to detect ultraviolet-induced reactive oxygen species (ROS) in the epidermis and the dermis of ex vivo human skin and skin equivalents. Skin is incubated with the nonfluorescent ROS probe dihydrorhodamine, which reacts with ROS such as singlet oxygen and hydrogen peroxide to form fluorescent rhodamine-123. Unlike confocal microscopic methods, two-photon excitation provides depth penetration through the epidermis and dermis with little photodamage to the sample. This method also provides submicron spatial resolution such that subcellular areas that generate ROS can be detected. In addition, comparative studies can be made to determine the effect of applied agents (drugs, therapeutics) upon ROS levels at any layer or cellular region within the skin.
Chapter
While an awareness of the harmful effects of sunlight are more appreciated today than ever before, more and more humans are exposing themselves to greater and greater doses of UV light. For the most part the source of this exposure is the sun, but exposure to artificial sources cannot be ignored. Fortunately public health messages warning about overexposure have become prominent and widespread and hence, over the past 10 years or so there has been an effort to increase sun protection either by recommending covering up or by recommending sunscreen use by people who need (or want) to spend more time outdoors.
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Para-aminobenzoic acid (PABA), once considered a vitamin, is a precursor of folate for certain bacteria and is used as a sunscreen because of its UV-absorbing property. In addition to its mild anti-inflammatory activity, recent studies demonstrate that PABA protects against photocarcinogenesis in hairless mice and nephrotoxicity of cis--diamminedichloroplatinum(II) in rats. However, little is known regarding the mechanism by which PABA exerts these effects. We have hypothesized that PABA may be an effective scavenger of reactive oxygen species. In this report, we showed that PABA reacted with hypochlorite in a ratio of reaction of 1:2, as measured by a spectrofluorometric method developed in this study. PABA reacted with hvdroxyl radicals (·OH) by inhibiting deoxyribose oxidation induced by a Fenton-type reaction system (Fe3+ + EDTA/H2OO2//ascorbic acid). The second-order rate constant for the reaction of PABA with ·OH was approximated 1.07 × 1010 M−1 s−1.. Electron spin resonance studies further demonstrated the reaction of PABA with ·OH. The Fenton-type reaction system also caused damage to calf thymus DNA, and concurrent treatment with UV (254 nm) enhanced the damage by 3 fold. PABA tested at 1.0 mM afforded 58% protection against such damage. Using rose bengal as a singlet oxygen (1OO2)) generator and ESR techniques, we showed that PABA scavenged 1OO2 more effectively than sodium azide, a known quencher of 1OO2.. However, PABA did not scavenge superoxide onions or react with H2OO2.. Thus, in addition to its UV absorbing ability, PABA effectively scavenges certain reactive oxygen species, an effect that may be relevant to its protection against photocarcinogenesis, inflammation, and drug toxicity.
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In addition to the four isomers of cyclobutane thymine dimer, two non-dimer photoproducts of thymine (5,6-dihydrothymine and 5-hydroxymethyluracil) were detected when free thymine base was irradiated at 324 nm in the presence of p-aminobenzoic acid (PABA) at pH 7.0. The yields were found to be enhanced in the presence of phosphate buffer. Irradiation of thymidine at 324 nm in the presence of PABA lead to the formation of 5,6-dihydrothymidine.
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Photoexcitations of aromatic carbonyl compounds possessing hydroxy groups ortho to the carbonyl group yield long-lived (∼10 -3 sec) triplet states only if the compounds are dissolved in solvents which are both rigid and relatively polar (especially if capable of hydrogen bonding). The results are consistent with the proposal 2,3 that in the molecules possessing an intramolecular hydrogen bond between the carbonyl oxygen and the hydroxyl hydrogen, very fast radiationless decay (perhaps from the singlet state precluding intersystem crossing) takes place.
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Use of sunscreens is widely advocated as a preventive measure against sun-induced skin cancers. However, to date, no epidemiologic study has reported a decreased melanoma risk associated with sunscreen use. We have conducted a case-control study aimed at evaluating the influence of sunscreen use on the occurrence of cutaneous malignant melanoma. In 1991 and 1992, 418 melanoma cases and 438 healthy controls were interviewed in Germany, France and Belgium. The questionnaire used differentiated between regular sunscreens, psoralen sunscreen (prepared with 5-methoxypsoralen, a tanning activator and photocarcinogen), and self-tanning cosmetics (which produce a tan without ultraviolet radiation). After adjusting for age, sex, hair colour and holiday weeks spent each year in sunny resorts, the melanoma risk was of 1.50 (95% CI:1.09–2.06) for regular sunscreens, and of 2.28 (95% CI: 1.28–4.04) for psoralen sunscreens. No melanoma risk was associated with use of self-tanning cosmetics. Among subjects with a poor ability to tan, psoralen sunscreen users displayed a melanoma risk of 4.45 (95% CI: 1.25–15.8) when compared with regular sunscreen users. There was a significant negative interaction between regular sunscreen use and sunburns experienced in adulthood. Use of sunscreens, especially psoralen sunscreen, was associated with higher density of pigmented lesions of the skin. Although we cannot exclude the presence of an unknown confounding factor, our results support the hypothesis that sunscreens do not protect against melanoma, probably because of their ability to delay or avoid sunburn episodes, which may allow prolonged exposure to unfiltered ultraviolet radiation. Serious doubts are raised regarding the safety of sunscreens containing psoralens. © 1995 Wiley-Liss, Inc.
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Topical sunscreens provide a means of sun protection and function by the absorption of light effecting an electronic excitation of the sunscreen, molecule (from its ground state to a first excited singlet state). Effective sunscreens are those that absorb strongly in the appropriate UV region, display good photostability and exhibit minor spectral modifications upon exposure to UV radiation and thermally dissipate the absorbed energy harmlessly. The most effective deactivation routes are internal conversion, vibrational relaxation and photoisomerisation. However, organic UV absorbers have the potential to form relatively long-lived triplet states, which can stimulate singlet oxygen production, effect transformations in biological substrates, such as thymine or in constituents of sunscreen formulations. This chapter is concerned with a critical assessment of the photochemical and photophysical properties of a range of commercially available organic (UVA and UVB) and inorganic sunscreens with respect to their efficacy and suitability as common sunscreen ingredients. We focus on the positive and negative attributes of the photochemical properties of sunscreens and consider the impact of published findings on sunscreen manufacturers and the development of new sunscreen agents. We conclude that may organic suncreens function by photoisomerisation, where isomeric mixtures serve as the major sun protection components. However, a number of sunscreens also form triplet states and singlet oxygen. Furthermore, inorganic sunscreens such as titanium dioxide and zinc oxide are known to degrade organic materials and produce hydroxyl radicals, although this is somewhat overcome by the use of surface treatment. Photoactivity testing of inorganic sunscreens is at an early stage of development and further work is required to achieve suitable protocols.
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Synopsis The application of a mathematical model to estimate the extent of transdermal absorption of UV-filters commonly used in sunscreen formulations is described. Percutaneous penetration is not a factor that has been properly addressed in the literature and the penetration/time profiles generated here suggest that significant amounts of certain of these compounds may penetrate the skin and enter the systemic circulation. The results presented indicate that further research in this area is necessary and the authors suggest that in vitro experiments with human skin are conducted with both current and new UV filters to quantify the degree of dermal penetration of these substances.
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Literature on the biological (mutagenesis) and molecular (DNA lesions and their cellular processing) events resulting from exposure of cells to solar ultraviolet and visible radiations is discussed. The problems encountered with research in this area are presented. Our sparse understanding of the complex mixture of events caused in cells by solar radiation and the mechanisms subserving these events is outlined.
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Several endogenous cellular constituents were tested for their ability to produce superoxide anion (O2-) from ground-state molecular oxygen upon irradiation by solar radiation. The pyridine cofactors NADPH and NADH, riboflavin, and the nucleosides 2-thiouracil and 4-thiouridine were found to sensitize the transmission of photon energy from solar radiation and monochromatic radiation (290, 334, 365, and 405 nm) to oxygen, resulting in O2- formation, as detected by superoxide dismutase-inhibitable cytochrome c reduction. Quantum yields for the production of O2- indicate that NADPH is the most efficient and riboflavin the least efficient of the compounds tested. These data indicate that endogenous compounds may participate in the production of O2- by solar radiation and imply that O2- may play a role in sunlight-induced erythema and dermal carcinogenesis.
Article
Exposure to ultraviolet radiation is the principle cause of basal and squamous cell carcinomas of the skin, which are the most frequent tumors occurring in white residents of the United States. Using a mathematical model based on epidemiologic data, we quantified the potential benefits of using a sunscreen with a sun protective factor of 15 and estimate that regular use of such a sunscreen during the first 18 years of life would reduce the lifetime incidence of these tumors by 78%. Additional benefits of sunscreen use during childhood include reduced risk of sunburn, retarding the pace of skin aging, and possible reduction in melanoma risk. We recommend that pediatricians encourage sunscreen use and sun avoidance as a regular part of pediatric preventive health care.
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In the presence of sunlamp radiation, p-aminobenzoic acid sensitizes pyrimidine dimer formation in the DNA of human skin fibroblasts. It also sensitizes the sunlamp-induced transformation of such cells to anchorage-independent growth.
Article
Use of sunscreens is widely advocated as a preventive measure against sun-induced skin cancers. However, to date, no epidemiologic study has reported a decreased melanoma risk associated with sunscreen use. We have conducted a case-control study aimed at evaluating the influence of sunscreen use on the occurrence of cutaneous malignant melanoma. In 1991 and 1992, 418 melanoma cases and 438 healthy controls were interviewed in Germany, France and Belgium. The questionnaire used differentiated between regular sunscreens, psoralen sunscreen (prepared with 5-methoxypsoralen, a tanning activator and photocarcinogen), and self-tanning cosmetics (which produce a tan without ultraviolet radiation). After adjusting for age, sex, hair colour and holiday weeks spent each year in sunny resorts, the melanoma risk was of 1.50 (95% Cl:1.09-2.06) for regular sunscreens, and of 2.28 (95% Cl: 1.28-4.04) for psoralen sunscreens. No melanoma risk was associated with use of self-tanning cosmetics. Among subjects with a poor ability to tan, psoralen sunscreen users displayed a melanoma risk of 4.45 (95% Cl: 1.25-15.8) when compared with regular sunscreen users. There was a significant negative interaction between regular sunscreen use and sunburns experienced in adulthood. Use of sunscreens, especially psoralen sunscreen, was associated with higher density of pigmented lesions of the skin. Although we cannot exclude the presence of an unknown confounding factor, our results support the hypothesis that sunscreens do not protect against melanoma, probably because of their ability to delay or avoid sunburn episodes, which may allow prolonged exposure to unfiltered ultraviolet radiation. Serious doubts are raised regarding the safety of sunscreens containing psoralens.
Article
Disruption of the zinc-thiolate center at the active site of yeast alcohol dehydrogenase results in inactivation and zinc release. Measurements of activity, zinc release, and thiol/thiolate oxidation were used to assess the effects of biologically relevant oxidants on alcohol dehydrogenase. Alcohol dehydrogenase was inactivated by 1 mM hydrogen peroxide at a rate of 1.3 M-1 s-1. Peroxynitrite, the near diffusion-limited reaction product of nitric oxide and superoxide, inactivated alcohol dehydrogenase with an IC50 = 0.95 microM when catalytic concentrations of alcohol dehydrogenase subunit (0.074 microM) were present. Slow, continuous production of peroxynitrite from decomposition of SIN-1 inactivated alcohol dehydrogenase as effectively as bolus addition. The rate constants for reaction of peroxynitrite with alcohol dehydrogenase at 23 degrees C as determined by two different competition assays were 2.6 x 10(5) M-1 s-1 and 5.2 x 10(5) M-1 s-1. The reaction with alcohol dehydrogenase represents one of the fastest reactions yet determined for peroxynitrite. Hypochlorite inactivated alcohol dehydrogenase at a rate of 4 x 10(3) M-1 s-1. The rate constant for inactivation by taurine choramine, the reaction product of taurine and hypochlorite, was only slightly slower at 2.7 x 10(3) M-1 s-1. Zinc release and thiol/thiolate oxidation were correlated with inactivation by either peroxynitrite or hypochlorite. At the concentrations of peroxynitrite or hypochlorite producing total inactivation, 0.85 zinc atom was released per subunit and 3 thiol/thiolates per subunit were oxidized.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
Nitric oxide reacts with superoxide to form peroxynitrite, which may be an important mediator of free radical-induced cellular injury. Oxidation of dihydrorhodamine to fluorescent rhodamine is a marker of cellular oxidant production. We investigated the mechanisms of peroxynitrite-mediated formation of rhodamine from dihydrorhodamine. Peroxynitrite at low levels (0-1000 nM) induced a linear, concentration-dependent, oxidation of dihydrorhodamine. Hydroxyl radical scavengers mannitol and dimethylsulfoxide had minimal effect (< 10%) on rhodamine production. Peroxynitrite-mediated formation of rhodamine was not dependent on metal ion catalyzed reactions because studies were performed in metal ion-free buffer and rhodamine formation was not enhanced in the presence of Fe3+ ethylenediaminetetraacetic acid (EDTA). Thus, rhodamine formation appears to be mediated directly by peroxynitrite. Superoxide dismutase slightly enhanced rhodamine production. L-cysteine was an efficient inhibitor (KI approximately 25 microM) of dihydrorhodamine oxidation through competetive oxidation of free sulfhydryls. Urate was also an efficient inhibitor (KI approximately 2.5 microM), possibly by reduction of an intermediate dihydrorhodamine radical and recycling of dihydrorhodamine. Under anaerobic conditions, nitric oxide did not oxidize dihydrorhodamine and inhibited spontaneous oxidation of dihydrorhodamine. In the presence of oxygen, nitric oxide induces a relatively slow oxidation of dihydrorhodamine due to the formation of nitrogen dioxide. We conclude that dihydrorhodamine is a sensitive and efficient trap for peroxynitrite and may serve as a probe for peroxynitrite production.
Article
Imaging techniques, such as confocal microscopy and fluorescent activated cells scan are facilitating the study of responses at the single-cell level. Superoxide is reported to oxidise the non-fluorescent dihydrorhodamine 123 (DHR) to rhodamine 123. The generation of rhodamine 123 by human neutrophils, stimulated by the phorbol ester phorbol 12-myristate 13-acetate was inhibited slowly by diphenylene iodonium and rapidly by azide, but not by superoxide dismutase. In the absence of enzymes H2O2 (but not O2-.) oxidised DHR slowly but the rate was greatly enhanced by peroxidases. The rhodamine 123 generated by phorbol-ester-stimulated neutrophils was observed to be located within the cell despite the fact that neutrophils failed to accumulate external rhodamine 123. This stimulated rise in cellular fluorescence was eliminated by excess extracellular catalase. It appears that H2O2, released on the outside, crosses the plasma membrane where oxidation of DHR is catalysed by cellular peroxidases. Since in a mixed population DHR failed to distinguish between O2-.-producing and non-producing HL60 cells it is not a suitable probe for single-cell observations. We conclude that DHR oxidation reports only the presence of H2O2 and intracellular peroxidases, and not the generation of O2-. by any one cell. Only peroxidase-containing cells fluoresce.
Article
Incidence rates of melanoma have risen especially steeply since the mid-1970s. The two principal strategies for reduction of risk of melanoma and other skin cancers are sun avoidance and use of chemical sunscreens. Rising trends in the incidence of and mortality from melanoma have continued since the 1970s and 1980s, when sunscreens with high sun protection factors became widely used. Commonly used chemical sunscreens block ultraviolet B (UVB) but are virtually transparent to ultraviolet A (UVA), which makes up 90 to 95% of ultraviolet energy in the solar spectrum. Because sunscreens prevent erythema and sunburn, and inhibit accommodation of the skin to sunlight, their use may permit excessive exposure of the skin to portions of the solar spectrum other than UVB. If melanoma and basal cell carcinoma are initiated or promoted by solar radiation other than UVB, as laboratory data suggest, then UVB sunscreens might not be effective in preventing these cancers, and sunscreen use might increase the risk of their occurrence. Alternative explanations for the rapid rise in the incidence and mortality rates of melanoma, such as changes in patterns of recreational sun exposure, are discussed. Traditional means of limiting overexposure to the sun, such as wearing of hats and adequate clothing and avoidance of prolonged sunbathing, may be more prudent than reliance on chemical sunscreens.
Article
2',7'-Dichlorofluorescein and dihydrorhodamine 123 were evaluated as probes for detecting changes in intracellular H2O2 in cultured endothelial cells. Stable intracellular levels of these probes were established within 15 min of exposure to the probe in culture medium. With continued presence of the probe in the medium, intracellular levels were unchanged for 1 h. However, if medium without the probes was used after intracellular loading had occurred, there was a greater than 90% loss of intracellular dichlorofluorescin, dichlorofluorescein, and dihydrorhodamine 123 while intracellular rhodamine 123 decreased by only 15%. Exposure of endothelial cells to exogenous 100 microM H2O2 for 1 h increased intracellular rhodamine 123 by 83%, but there was a reproducible decrease of 53% in intracellular dichlorofluorescein. Exposure to 0.05 mM BCNU plus 10 mM aminotriazole for 2 h increased intracellular rhodamine 123 by 111%. In vitro studies of dihydrorhodamine 123 oxidation were similar to previous reports of dichlorofluorescin oxidation. Oxidation of dihydrorhodamine 123 does not occur with H2O2 alone, but is mediated by a variety of secondary H2O2-dependent intracellular reactions including H2O2-cytochrome c and H2O2-Fe2+. Our results suggest that detection of increased oxidation of these probes in endothelial cells is most useful as a marker of a change in general cellular oxidant production.
Article
Evidence is presented for the photochemical formation of singlet molecular oxygen (1O2) in air-saturated buffered aqueous solutions of p-aminobenzoic acid (PABA) using sunlight-range illumination. This is significant because PABA is widely used as an active ingredient in sunscreen preparations that are applied to the surface of the skin and 1O2 is known to cause oxidative damage to cells via the formation and subsequent reactions of lipid peroxides. Furfuryl alcohol (FFA), a well known chemical trap for 1O2, was added to aqueous PABA solutions prior to illumination. The FFA was consumed when the solution was illuminated, but no loss of FFA occurred in the dark and loss by direct photolysis was negligibly slow. Further evidence for the formation of 1O2 in illuminated aqueous PABA solutions is provided by the results of experiments in which individual solutions containing PABA and FFA that were diluted with D2O exhibited an increased rate of FFA consumption due to the increased lifetime and concentration of 1O2 in this solvent.
Article
Evidence is presented for the photochemical formation of singlet molecular oxygen (1O2) in air-saturated aqueous solutions of several sunscreen active ingredients using sunlight-range illumination. This is of significance because (1) 1O2 is known to be cytotoxic, and (2) there have been several reports of toxic effects associated with the use of some sunscreens; most notably, with p-aminobenzoic acid (PABA). Illuminated aqueous solutions of PABA, 2-ethylhexyl p-(dimethylamino)benzate (ODPABA), 2-hydroxy-4-methoxybenzophenone (BZ3), 2,2'-dihydroxy-4-methoxybenzophenone (BZ8), 2-ethylhexyl 2-cyano-3,3-diphenylacrylate (OCR), 2-ethylhexyl p-methoxycinnamate (OMC), and 2-ethylhexyl salicylate (OCS) were evaluated individually for 1O2 formation. Furfuryl alcohol (FFA), a well-known chemical trap for 1O2, was added to each of the aqueous sunscreen solutions. The FFA was consumed when solutions of PABA, ODPABA, OMC, and OCR were illuminated, but no loss of FFA other than by direct photolysis occurred in solutions of BZ3, BZ8, or OCS. There was also no significant loss of FFA in any of these solutions kept in the dark. Further evidence for the formation of 1O2 in illuminated aqueous sunscreen solutions is provided by the results of experiments in which individual solutions containing sunscreen active ingredients and FFA that were diluted with D2O exhibited an increased rate of FFA consumption while the addition of azide ion (N3-) reduced the rate of FFA consumption. Continuous sunlight-range illumination of aqueous PABA solutions produced significantly higher steady-state concentrations of 1O2 than in solutions containing any of the other sunscreen active ingredients evaluated. The substituted benzophenone compounds (BZ3 and BZ8) and the salicylate-based compound (OCS) not only appear to produce no 1O2, but they also appear to produce no other reactive oxidant species that are capable of consuming FFA. This indicates that BZ3, BZ8, and OCS may be peferable, from the standpoint of toxic oxidant formation, for use as sunscreen active ingredients when compared to the other compounds evaluated in this study.
Article
In order to improve our knowledge on the efficacy and safety of sunscreen products, we measured the skin penetration profiles of ultra-violet (UV) filters in vitro and in vivo, and the corresponding sun protection factors (SPF) from two vehicles (an O/W emulsion-gel and petroleum jelly). The UV filters tested were oxybenzone (5%, A), 2-ethylhexyl 4-methoxycinnamate (7.5%,B), and 2-ethylhexylsalicylate (3%,C). Two mg/cm(2) were applied for 2 min to 6 h. In vitro penetration measurements were performed with static diffusion cells. In vivo, horny layer concentrations were measured after stripping and the SPF evaluated as recommended by the COLIPA-guidelines. Significant differences between vehicles were noticed in vitro as well as in vivo. In vitro, the emulsion-gel generated higher epidermal concentrations than petroleum jelly. Values at 6 h, expressed as percent of the applied dose for A, B, and C were 4, 9, and 7% for the emulsion-gel and 2, 1, and 2% for petroleum jelly. An opposite trend was noticed, mainly for A, in the deeper skin layers with concentrations of 2% in the dermis and 5% in the receptor fluid for petroleum jelly and 0.6% and 1% for the emulsion-gel respectively. In vivo, for each UV filter, maximal stratum corneum levels (15 strips) were obtained at 0.5 h with percentages of the applied doses of 50% for the emulsion-gel and 15 percent for petroleum jelly. SPFs, measured 0.5 h after application amounted to 14 for the emulsion-gel and 5 for petroleum jelly, and decreased in both cases by a factor 2.2 after removal of non penetrated product. These preliminary results demonstrated that UV filters penetration and retention as well as expected SPF could be optimized by a suitable vehicle.
Article
Ultraviolet radiation produces free radicals in Skh-1 mouse skin, contributing to photoaging and carcinogenesis. If a mouse model is a general indicator of free radical processes in human skin photobiology, then radical production observed in mouse and human skin should be directly comparative. In this work we show that UV radiation (lambda > 300 nm, 14 microW/cm2 UVB; 3.5 mW/cm2 UVA) increases the ascorbate free radical (Asc.-) electron paramagnetic resonance (EPR) signal in both Skh-1 mouse skin (45%) and human facial skin biopsies (340%). Visible light (lambda > 400 nm; 0.23 mW/cm2 UVA) also increased the Asc.- signal in human skin samples (45%) but did not increase baseline mouse Asc.-, indicating that human skin is more susceptible to free radical formation and that a chromophore for visible light may be present. Using EPR spin-trapping techniques, UV radiation produced spin adducts consistent with trapping lipid alkyl radicals in mouse skin (alpha-[4-pyridyl 1-oxide]-N-tert-butyl nitrone/alkyl radical adduct; aN = 15.56 G and aH = 2.70 G) and lipid alkoxyl radicals in human skin (5,5-dimethylpyrroline-1-oxide/alkoxyl radical adduct; aN = 14.54 G and aH = 16.0 G). Topical application of the iron chelator Desferal to human skin significantly decreases these radicals (approximately 50%), indicating a role for iron in lipid peroxidation; Desferal has previously been shown to decrease radical production in mouse skin. This work supports the use of the Skh-1 mouse as a predictive tool for free radical formation in human skin. These results provide the first direct evidence for UV radiation-induced free radical formation at near physiological temperatures in human skin and suggest that iron chelators may be useful as photoprotective agents.
Article
The relationship between mitochondrial membrane permeability transition (MPT) and the toxic effects of the alkyl esters of p-hydroxybenzoic acid (parabens) has been studied in mitochondria and hepatocytes isolated from rat liver. MPT has been proposed as a common final pathway in acute cell death through mitochondrial dysfunction. In isolated mitochondria, propyl-paraben (0.1 to 0.5 mM) in the presence of Ca2+ (50 microM) elicited a concentration-dependent induction of mitochondrial swelling dependent on MPT. This was prevented by pretreatment with a specific inhibitor of MPT, cyclosporin A (0.2 microM). For the other parabens tested, the induction of MPT depended on the relative elongation of alkyl side-chains in their molecular structure and was associated with the partition coefficients. In contrast, the induction caused by p-hydroxybenzoic acid was more potent than that of methyl- or ethyl-paraben. The pretreatment of freshly isolated hepatocytes with cyclosporin A (5 microM) and trifluoperazine (10 microM), which inhibit MPT in a synergistic manner, partially but not completely prevented propyl-paraben (1 mM; plus diazinon, 100 microM)-induced cell death, ATP loss, and decreased mitochondrial membrane potential. These results suggest that the onset of paraben-induced cytotoxicity is linked to mitochondrial failure dependent upon induction of MPT accompanied by the mitochondrial depolarization and depletion of cellular ATP through uncoupling of oxidative phosphorylation.
Article
In recent years it has become apparent that the oxidation of lipids, or lipid peroxidation, is a crucial step in the pathogenesis of several disease states in adult and infant patients. Lipid peroxidation is a process generated naturally in small amounts in the body, mainly by the effect of several reactive oxygen species (hydroxyl radical, hydrogen peroxide etc.). It can also be generated by the action of several phagocytes. These reactive oxygen species readily attack the polyunsaturated fatty acids of the fatty acid membrane, initiating a self-propagating chain reaction. The destruction of membrane lipids and the end-products of such lipid peroxidation reactions are especially dangerous for the viability of cells, even tissues. Enzymatic (catalase, superoxide dismutasse) and nonenzymatic (vitamins A and E) natural antioxidant defence mechanisms exist; however, these mechanisms may be overcome, causing lipid peroxidation to take place. Since lipid peroxidation is a self-propagating chain-reaction, the initial oxidation of only a few lipid molecules can result in significant tissue damage. Despite extensive research in the field of lipid peroxidation it has not yet been precisely determined if it is the cause or an effect of several pathological conditions. Lipid peroxidation has been implicated in disease states such as atherosclerosis, IBD, ROP, BPD, asthma, Parkinson's disease, kidney damage, preeclampsia and others.
Article
Sunscreen is used as a primary strategy to prevent sunburn and later skin cancer. However, sunscreen use has paradoxically been associated with the increasing incidence of skin cancer. One explanation for this puzzling observation is sunscreen failure (sunburn in the setting of sunscreen). Our purpose was to evaluate mechanisms of sunscreen failure in a sunscreen-using population. We carried out an epidemiologic comparison of sunburned and nonsunburned beachgoers who used sunscreen. We found that men were less likely to use sunscreen than women (chi(2) = 11.3, df = 1, P = .001), and when it was used, men were less likely to apply sunscreen to all sunlight-exposed skin (chi(2) = 18.4, df = 1, P = .0001). Swimmers who used sunscreen were significantly more likely to be sunburned compared with nonswimming sunscreen users (Fisher exact test, df = 1). Sunscreen may fail to prevent sunburn if it is washed off during swimming or if it is not applied to all exposed skin. Epidemiologic studies that link sunscreen use to skin cancer should evaluate whether sunburn occurred in this setting.
Article
The sunscreen agent 2-phenylbenzimidazole-5-sulfonic acid (PBSA) and its parent 2-phenylbenzimidazole (PBI) cause DNA photodamage via both Type-I and Type-II mechanisms when UVB irradiated. We have studied the photophysical and photochemical properties of these compounds and their ability to photogenerate reactive oxygen species including free radicals. PBI and PBSA exhibit both oxidizing and reducing properties in their excited state. The absorption and fluorescence properties of PBSA depend strongly upon pH, and hence the photochemistry of PBSA was studied in both neutral and alkaline solutions. PBSA showed strong oxidizing properties when UV irradiated in neutral aqueous solution (pH 7.4) in the presence of cysteine, glutathione and azide, as evidenced by the detection of the corresponding S-cysteinyl, glutathiyl and azidyl radicals with the aid of the spin trap, 5,5-dimethyl-1-pyrroline N-oxide (DMPO). However, when an aqueous anaerobic solution (pH 10) of PBSA and either nitromethane (NM) or 4-nitrobenzoic acid (4-NBA) were irradiated, the corresponding nitro anion radicals were observed. This finding suggests that both NM and 4-NBA are reduced by direct electron transfer from the excited state PBSA. During UV irradiation of an aerobic solution of PBSA, O2*- and *OH radical were generated and trapped by DMPO. Further, PBI (in ethanol) and PBSA (in ethylene glycol : water 2: 1 mixture) showed low temperature (77 K) phosphorescence (lambdamax = 443, 476 and 509 nm) and also an electron paramagnetic resonance half-field transition (deltaMs = +/-2), which is evidence for a triplet state. This triplet produced singlet oxygen (1O2) with quantum yields 0.07 and 0.04 in MeCN for PBI and PBSA, respectively. These studies demonstrate that UV irradiation of PBSA and PBI generates a variety of free radicals and active oxygen species that may be involved in the photodamage of DNA.
Article
Cutaneous malignant melanoma is the most serious form of skin cancer and accounts for about three-quarters of all skin cancer deaths. Over the last few decades the incidence and mortality rates of melanoma have been increasing worldwide. The risk of melanoma is higher in individuals with both phenotypic susceptibility and a history of sun exposure. Therefore, recommended sun protection behaviours include wearing long-sleeved clothing, seeking shade, avoiding the sun when it is strongest, and using sunscreen lotion with a sun protection factor of 15 or higher. It has been reported, however, that the use of sunscreens does not protect against melanoma and seems to increase the duration of recreational sun exposure. Published epidemiological studies examining sunscreen use and melanoma have been reviewed from an epidemiological point of view, taking into account potential biases. We have classified case-control studies into four categories: (1) inconclusive studies because of major bias in control population and/or the lack of multivariate analysis; (2) no association between sunscreen use and melanoma after controlling for confounders; (3) negative association (i.e. protective effect of sunscreen); and (4) positive association. Various other epidemiological studies were also analysed. These results are controversial. Two case-control studies show a protective effect of sunscreen use, while three studies showed a significant risk associated with sunscreen use. However, the discordant results, the low relative risks, the lack of dose-effect relationship and the numerous biases, especially the uncertainty that exposure (sunscreen use) preceded melanoma do not suggest a causative association between sunscreen use and melanoma. Several hypotheses could partly explain these contradictory results.