Sunscreens and phototesting

The last decade has seen numerous advances in the development of photoprotective sunscreens. There have been significant improvements in the sunscreening chemicals as well as vehicle preparations, yielding much higher protection factors and enhanced substantivity. In addition, novel sunscreening chemicals are currently being explored that provide protection against ultraviolet A (UVA) radiation. This chapter briefly describes both traditional and novel methods for evaluating sunscreening agents, discusses the recent evidence supportive of the view that UVA and infrared radiation exert pathologic changes in the skin, and provides the private dermatologist with additional information by which he or she can better understand the sunscreen literature and manufacturers' claims.     

Cutaneous photoprotection from ultraviolet injury by green tea polyphenols

BACKGROUND: In animal models, extracts from green tea have been shown to be remarkably effective at reducing the severity of adverse human health effects of overexposure to ultraviolet (UV) radiation. Although sunscreens and other photoprotective measures have traditionally been used for this purpose, there is a need for additional measures and natural products are increasingly being explored for that purpose. OBJECTIVE: Our purpose was to evaluate the effect of polyphenols from green tea on parameters associated with acute UV injury. METHODS: Areas of skin of normal volunteers were treated with an extract of green tea or one of its constituents. Thirty minutes later, the treated sites were exposed to a 2 minimal erythema dose solar simulated radiation. UV-treated skin was examined clinically for UV-induced erythema, histologically for the presence of sunburn cells or Langerhans cell distributions, or biochemically for UV-induced DNA damage. RESULTS: Application of green tea extracts resulted in a dose-dependent inhibition of the erythema response evoked by UV radiation. The (-)-epigallocatechin-3-gallate (EGCG) and (-)-epicatechin-3-gallate (ECG) polyphenolic fractions were most efficient at inhibiting erythema, whereas (-)-epigallocatechin (EGC) and (-)-epicatechin (EC) had little effect. On histologic examination, skin treated with green tea extracts reduced the number of sunburn cells and protected epidermal Langerhans cells from UV damage. Green tea extracts also reduced the DNA damage that formed after UV radiation. CONCLUSION: Polyphenolic extracts of green tea are effective chemopreventive agents for many of the adverse effects of sunlight on human health and may thus serve as natural alternatives for photoprotection.     

The beneficial role of functional food components in mitigating ultraviolet‐induced skin damage

Excessive exposure to ultraviolet (UV) radiation can chemically alter biological molecules and is one of the major environmental health risks with potential to damage the structure and function of the skin. Numerous dietary supplements are known to optimize the skin's defenses against radiation exposure. Several studies in which the beneficial roles of functional food components, that can protect against UV‐induced skin damage, have been demonstrated. Supplemental dietary sphingomyelin maintains covalently bound ω‐hydroxy ceramides to avert skin barrier defects after UVB irradiation. The oral administration of collagen hydrolysates has been shown to limit decreases in skin elasticity via increases in the dermal hyaluronic acid content. Milk fermented with lactic acid bacteria has been shown to augment DNA repair mechanisms and improve skin immunity in the aftermath of UVB damage. Furthermore, long‐term ingestion of fermented milk containing lactic acid bacteria, collagen hydrolysates and sphingomyelin increases the minimal erythema dose (MED) in human subjects with moderate sunburn or redness and tanned skin after exposure to UV solar radiation. Thus, products containing these functional food components are one means by which the adverse effects of UV radiation on the skin can be mitigated.     

Skin nonpenetrating sunscreens for cosmetic and pharmaceutical formulations

Ultraviolet (UV) solar radiation produces harmful effects on the skin including sunburn, local immunosuppression, skin photoaging, and cutaneous malignancies. Although application of sunscreens is the "gold standard" for protecting the skin from UV radiation, studies have shown that currently used sunscreens can cause adverse skin and systemic reactions, owing to their penetration into the viable cutaneous strata and to transdermal absorption. This paper presents new nonpermeating sunscreens (NPSUN) suitable for use in cosmetic and pharmaceutical products. The basic idea behind the design of the new photoprotectors was to immobilize UV-absorbing moieties in the Jojoba oil chemical backbone. The physicochemical characteristics of NPSUNs allow these derivatives to remain confined to the upper stratum corneum where the sunscreen molecule acts, with no further clearance to deeper dermal strata or systemic circulation. As an example, no permeation across the skin of methoxycinnamate-NPSUN was observed during 24-hour in vitro experiments, after topical application of either unformulated substances or of methoxycinnamate-NPSUNs formulated in oil-in-water cream, in water-in-oil cream, or in Jojoba oil. Another approach to increase the photoprotective effect against the UV radiation is targeting the delivery of alpha tocopherol into the deeper skin layers and across the cell membranes. This is necessary for optimal photoprotection and prevention of malignant processes. For this purpose, ethosomal vitamin E compositions were designed, characterized, and tested. Efficient intracellular and dermal accumulation of vitamin E from ethosomes was demonstrated. A good clinical strategy could be the use of NPSUNs during direct UV exposure followed by the application of alpha-tocopherol compositions after short- or long-term solar radiation.     

A review of sunscreens and their adverse reactions

Sunscreens are used to protect the skin from harmful effects of ultraviolet (UV) light but they do not completely prevent photocarcinogenesis, photoaging and photoimmunosuppression. They are useful for protection against UVB and short-wave UVA. Complete protection against long-wave UVA has not been achieved. There is no universally accepted method to evaluate UVA protection. Sun protection factor is a simple and internationally used method to compare sunscreen protection against UVB induced erythema. Adverse reactions to sunscreens are not common but they should be considered especially in persons with pre-existing eczematous conditions or photodermatoses. The use of sunscreens has increased steadily over the last decade; as a result, allergy and photoallergy to UV filters are now more frequent than in the past. Sensitization can occur from the various sunscreening agents and from the excipients included in formulations. An overview of sunscreens, their effectiveness, and adverse reactions is presented.     

Skin photoprotection by natural polyphenols: anti-inflammatory, antioxidant and DNA repair mechanisms

Epidemiological, clinical and laboratory studies have implicated solar ultraviolet (UV) radiation in various skin diseases including, premature aging of the skin and melanoma and non-melanoma skin cancers. Chronic UV radiation exposure-induced skin diseases or skin disorders are caused by the excessive induction of inflammation, oxidative stress and DNA damage, etc. The use of chemopreventive agents, such as plant polyphenols, to inhibit these events in UV-exposed skin is gaining attention. Chemoprevention refers to the use of agents that can inhibit, reverse or retard the process of these harmful events in the UV-exposed skin. A wide variety of polyphenols or phytochemicals, most of which are dietary supplements, have been reported to possess substantial skin photoprotective effects. This review article summarizes the photoprotective effects of some selected polyphenols, such as green tea polyphenols, grape seed proanthocyanidins, resveratrol, silymarin and genistein, on UV-induced skin inflammation, oxidative stress and DNA damage, etc., with a focus on mechanisms underlying the photoprotective effects of these polyphenols. The laboratory studies conducted in animal models suggest that these polyphenols have the ability to protect the skin from the adverse effects of UV radiation, including the risk of skin cancers. It is suggested that polyphenols may favorably supplement sunscreens protection, and may be useful for skin diseases associated with solar UV radiation-induced inflammation, oxidative stress and DNA damage.     

The sunscreening effect of urocanic acid

Urocanic acid (UCA), present in the stratum corneum, is a major absorber of ultraviolet (UV) radiation and, on UV exposure, is induced to isomerize from the naturally occurring trans-isomer to the cis-isomer. Cis-UCA has been shown to have immunosuppressive properties, while trans-UCA may act as a natural sunscreen due to its UV-absorbing properties. The photoprotective capacity of UCA was investigated in this study. Minimal erythema dose (MED) was determined on normal buttock skin in 36 healthy subjects and the concentration of UCA isomers was measured on the skin adjacent to the test site. On the contralateral buttock, MED was determined 20 min after application of trans-UCA 5% in a cream base. The UCA cream gave a sun protection factor of 1.58. The amount of UCA applied was, however, 20–200 times higher than the amount of UCA found in normal skin, making a sunscreening effect of naturally occurring UCA very low This was further supported by a lack of correlation between naturally occurring UCA and the UV sensitivity of each subject determined by the MED.     

Assessment of the skin photoprotective capacities of an organo-mineral broad-spectrum sunblock on two ex vivo skin models

UV irradiation can cause cutaneous damage that may be specific according to the wavelength of UV rays. For example, damage from UVB irradiation manifests itself in the form of sunburn cells and enhancement of the expression of p53, while damage from UVA exposure results in an increase in the expression of vimentin. These reactions to UV irradiation were used in this work to evaluate the photoprotective capacities of two sunblock preparations that were applied to the surface of the skin. One sunblock preparation is a UVB absorber containing zinc oxide (ZnO) and titanium oxide (TiO2) exclusively. The other sunblock preparation is a new organo-mineral sunblock containing Tinosorb M, OCM, ZnO and TiO2. Evaluation of the photoprotective capacities of both preparations on hairless rat skin and on in vitro reconstructed human epidermis revealed that they were effective in preventing UVB-induced damage. In contrast, only the organo-mineral sunblock was effective in the prevention of UVA-specific damage such as dermal alterations characterized by the expression of vimentin. Furthermore, our data support the fact that hairless rat skin and in vitro reconstructed human epidermis are a reliable basis for the evaluation of the photoprotective capacities of various sunscreens against UVB and UVA damage.     

Evaluation of sunscreening agents

Sunscreen preparations are evaluated according to their protection against biological effects of ultraviolet radiation. UV-induced phenomena found on protected skin are compared with those on unprotected skin; thus the sunprotection factor is estimated. In order to assess the photoprotective power of sunscreens, only early UV-induced effects are decisive - such as erythema. PUVA erythema, pigmentation, activation of the ornithine decarboxylase, the influence on Langerhans cells, appearance of 'sunburn' cells, and changes of the DNA metabolism. We report on the various methods to obtain the specific sunprotection factors against UVB and UVA. Water-resistance, photostability, and pharmacokinetics depending on the vehicle are further criteria with regard to the evaluation of sunscreens. We rely on consumers information regarding the following properties of sunscreens: stickness, oily shine, greasiness, discoloration, odor, and tolerance.     

Photoprotective effects of green tea polyphenols

Non-melanoma skin cancer is the most common malignancy in humans and is equivalent to the incidence of malignancies in all other organs combined in the United States. Current methods of prevention depend on sunscreens in humans, efficacy of which is largely undetermined for non-melanoma skin cancers. Green tea polyphenols have the greatest effect with respect to chemoprevention and have been found to be most potent at suppressing the carcinogenic activity of UV radiation. They protect against many of the other damaging effects of UV radiation such as UV-induced sunburn response, UV-induced immunosuppression and photoaging of the skin. They exert their photoprotective effects by various cellular, molecular and biochemical mechanisms in in vitro and in vivo systems. Green tea polyphenols thus have the potential, when used in conjunction with traditional sunscreens, to further protect the skin against the adverse effects of ultraviolet radiation.     

Effect of topical application of antioxidants and free radical scavengers on protection of hairless mouse skin exposed to chronic doses of ultraviolet B

Background/aims: Within the past three decades, there has emerged a greater awareness of the molecular effects of solar rays especially ultraviolet radiation (UV-R), to the extent that the harmful effects of solar radiation are recognized not only by molecular biologists and physicians, but also by the general public (1). Various sunscreen molecules that effectively block the UVB component of the sun are available; however, a large part of Western populations elicits adverse reactions against chemical sunscreens (2). This study was designed to observe the protective effect of antioxidants against the damaging effects of chronic UVB exposure of skin in an attempt to introduce antioxidants and free radical scavengers as topical sun protective agents. Methods: Jackson hairless mice were exposed to suberythemal doses of UVB, three times a week, and topically treated with a cream containing the anti-oxidants vitamin E, butylated hydroxy-toluene, nordihydroguaradinic acid and vitamin C. Results: Treatment with vehicle alone along with UVB exposure resulted in an increase in epidermal thickness showing a 38%, 77% and 112% increase after 4 weeks, 8 weeks and 12 weeks, respectively. Chronic UVB exposed skin treated with the material containing free radical scavengers and antioxidants mix (AO mix) exhibited 39%, 73% and 124% thicker epidermis than the un-treated control after, respectively, 4 weeks, 8 weeks and 12 weeks of treatment. The vehicle did not appear to protect skin against UV irradiation, since there appeared to be more (16%) sunburn cells in vehicle treated skin than the untreated, UV exposed skin after 4 weeks of treatment. After 8 weeks and 12 weeks, there were 33% and 36% less sunburn cells in the vehicle treated skin than the untreated, UV exposed skin. The antioxidant mix was significantly effective (P=<0.001) in protecting against UVB irradiation, having 63%, 71 % and 79% fewer sunburn cells than the untreated, UV exposed skin after 4 weeks, 8 weeks and 12 weeks of treatment, respectively. Conclusion: Data from these studies suggest that low level chronic exposures to UV can lead to alteration of the skin, like epidermal thickening and appearance of sunburn cells. The data also indicates that a mix of common antioxidants and free radical scavengers are photoprotective against chronic skin damage in the hairless mouse skin model.     

Biomelanin antioxidants in cosmetics: assessment based on inhibition of lipid peroxidation

Acute adverse effects of ultraviolet (UV) radiation in humans include sunburn, photosensitivity reactions and immunological suppression. Chronic exposure to UV light, particularly the UVB (290-320 nm) component of the UV radiation, and certain environmental chemicals increase the risk of nonmelanoma skin cancer and play a major role in cutaneous aging. The lipid peroxidation (LPO) of biomembranes, mediated by reactive oxygen species and free radicals, is one of the major causes of cellular damage induced by UV radiation and toxins. Antioxidants, such as vitamin E, vitamin C and melanins, are reactive oxygen and radical scavengers, thereby minimizing the light- and toxin-induced tissue destruction. We examined the influence of 8 biotechnically produced polyphenolic melanins on the LPO of microsomal membranes in comparison with alpha-tocopherol, ascorbate and synthetic melanin. All biomelanins showed better inhibition of peroxidative damage than synthetic melanin. Three of the 8 tested drugs inhibited the LPO at least as effectively as vitamin C and vitamin E. The combination of the most effective biomelanin with both vitamin C and vitamin E resulted in greater LPO inhibition than caused by each agent alone. Our data show that biomelanins are potent inhibitors of the peroxidative destruction of biomembranes, indicating that these compounds may be useful antioxidative agents in cosmetic preparations.     

Photoprotective effect of topical anti-inflammatory agents against ultraviolet radiation-induced chronic skin damage in the hairless mouse

Albino hairless mice (Skh:HR-1) exposed chronically to suberythemal doses of ultraviolet (UV) radiation display visible and histological alterations in the skin. One alteration is an increase in dermal cellularity, including inflammatory cells. This suggested a role for inflammation in chronic photodamage. We evaluated the photoprotective effect of topical hydrocortisone, ibuprofen, and naproxen against photodamage. All 3 agents protected against UVB radiation-induced visible wrinkling, tumor formation, and histological alterations. Hydrocortisone and naproxen were also evaluated for protection against UVA radiation-induced visible skin sagging and histological alterations. Both were very effective. These data indicate that chronic topical application of anti-inflammatory agents provides broad solar UV spectrum photoprotection.     

Topical indomethacin protects from UVB and UVA irradiation

Conclusions Indomethacin is known to decrease the UVB (290–310 nm) induced erythema when applied topically in regular intervals after irradiation [2,5,6], probably via inhibition of prostaglandin synthesis. The absorption spectrum of an IM solution (Fig. 1) suggests that this drug may also exert a high filter capacity in the UVB and UVA range, when applied as a topical suncreen before exposure to UV light. The present study demonstrates that a 2.5% solution of IM indeed protects from UVB induced erythema, and these results are in accordance with those of Lim et al., recently published in abstracted form (1983). The present study demonstrates that topically aplied IM exerts a photoprotective effect also at the cellular level since it prevents UV induced keratinocyte cell death (formation of sunburn cells).Topical application of 2.5% IM decreases the induction of PUVA erythema and inhibits the development of immediate pigment darkening, which demonstrates a potent photoprotective effect also in the UVA range.The photoprotective mechanism of IM when applied prior to irradiation seems to be a filter effect (as to be expected from the absorption spectrum) rather than a biochemical action such as inhibition of prostaglandin synthesis, although the latter explanation cannot be excluded completely from the present results. Preliminary data, however, indicate that sunburn cells do occur in skin irradiated with erythemogenic doses of UVB light and treated with topical IM after exposure, which prevents erythema formation. Before IM can be widely used, it is necessary to evaluate optimal concentration and vehicles and in particular percutaneous absorption and possible systemic toxicity. The UVB screening potency of topical IM seems to be similar to other sunscreens (e.g. para-aminobenzoic acid/PABA), but IM offers a much higher protection against UVA light. This may be important in the treatment of certain photodermatoses and also in the prevention of elastotic skin damage by sunlight.     

Effect of pre-treatment of almond oil on ultraviolet B-induced cutaneous photoaging in mice

Background Ultraviolet (UV) radiation has been implicated in photoaging and various types of skin carcinomas. Although the human skin has evolved several defense mechanisms to survive the insults of actinic damage like keratinization, melanin pigmentation, etc., it is still subjected to the harmful effects of sunlight. Aims In this study, the role of almond oil in reducing the degradative changes induced in skin upon exposure to UV radiation was investigated. Methods Mice were divided in four groups of 20 animals. Group I was the control group. Group II was negative control, which received almond oil treatment alone. Group III was exposed to UV radiation only and Group IV received both UV treatment and almond oil treatment. Visible skin grading assessed the changes based on a rating scale, biochemical tests (glutathione estimation and lipid peroxidation), and histopathologic studies. Results Upon exposure of mice to UV radiation, it was found that pronounced visible skin changes were seen after 12 weeks of exposure. The results of the biochemical tests, glutathione estimation, and lipid peroxidation showed that almond oil reduced the effect of UV light–induced photoaging on the skin. Histopathologic studies also indicated a photoprotective effect of almond oil on the skin after UV exposure. Conclusions It was concluded that topical almond oil is capable of preventing the structural damage caused by UV irradiation and it was also found useful in decelerating the photoaging process.     

Erythema and melanogenesis action spectra in heavily pigmented individuals as compared to fair-skinned Caucasians

The protective role of epidermal melanin pigmentation against chronic exposure to ultraviolet radiation is widely accepted, although its photoprotective effect against acute exposure is less certain. In this study, the action spectra of erythema and melanogenesis in heavily pigmented individuals (skin type V) were determined at 295, 305, 315, and 365 nm, and compared with those of skin types I and II. When the erythema and melanogenesis action spectra for skin type V were normalized to 295 nm, they were identical to the corresponding action spectra for fair-skinned individuals, indicating that the photoprotection of epidermal melanin pigmentation is essentially independent of wavelength. The ratio of values for the minimum erythema dose (MED) between skin type V and skin types I and II was 2.29, which is close to the ratio of pigment in these skin types, as measured by diffuse reflectance spectroscopy in the visible range. The minimum immediate pigment darkening dose (IPD) and the minimum melanogenic dose (MMD) at 365 nm, and the MED and MMD at 315 nm were the same for all skin types, while the variation of MED for every skin type was maximum at 305 and 365 nm. The results provide circumstantial evidence that erythema and melanogenesis have the same mechanism at short-wavelength UVB (295 and 305 nm), and different mechanisms in UVA (365 nm). Furthermore, the 24 h MED at 305 nm appears to be a sensitive indicator of skin type.     

In vivo and in vitro evaluation of the use of a newly developed melatonin loaded emulsion combined with UV filters as a protective agent against skin irradiation

BackgroundMelatonin has attracted attention because of their high antioxidant and anticarcinogenic activity. Otherwise, the use of sunscreens is recommended for patients after chemotherapy and radiotherapy treatments or to prevent UV radiation-induced skin damages that may result in pre-cancerous and cancerous skin lesions.ObjectiveTo evaluate the beneficial influence of melatonin in topical sunscreen emulsions combined with three common ultraviolet filters.MethodsAfter the formulation characterization in terms of rheology, stability studies were performed. Release studies let us to evaluate its mechanism of delivery and ex vivo permeation study through human skin, the amount of melatonin retained. The antioxidant activity assay was also carried out, and finally the in vivo photoprotective effect in rats was tested as transepidermal water loss and erythema formation.ResultsThe rheological behaviour of formulations was pseudoplastic fluid, all emulsions had good physical stability. Release studies showed a trend of enhancement in melatonin release from emulsions incorporating UV filters and followed a Weibull model. Melatonin permeation was higher from the emulsion containing melatonin combined with a mixture of three ultraviolet filters (MMIX) formulation. Equally this formulation exhibited the highest radical scavenging activity. Finally the photoprotective assay showed that only skin areas treated with this formulation were statistically equivalent to the unirradiated control area.ConclusionMMIX formulation would be a promising formulation for preventing the undesirable adverse effects of UV skin irradiation because melatonin not only acts as a potent antioxidant itself, but also is capable of activating an endogenous enzymatic protective system against oxidative stress.     

Photoprotective effect of calcipotriol upon skin photoreaction to UVA and UVB

It has been shown that 1,25-dihydroxyvitamin D₃ has a photoprotective effect against UVB injury in mouse skin and cultured rat keratinocytes by induction of metallothionein (MT). Calcipotriol is a synthetic analogue of 1,25-dihydroxyvitamin D₃ with equipotent cell regulating properties, but with a lower risk of calcium-related side effects. The aim of the present study was to see whether calcipotriol has a photoprotective property both in vitro and in vivo. We examined the effect of calcipotriol on UV-induced damage of cultured human keratinocytes through a cell viability assay, and measurement of DNA synthesis by cultured keratinocytes, on UV-induced damage of mouse skin and on minimal erythema dose (MED). We found that calcipotriol was protective against UVB-induced reduction in DNA synthetic activity of cultured keratinocytes in relatively low doses (20 and 40 mJ/cm²) of UVB. With phototesting following application of calcipotriol, five subjects among 10 healthy volunteers and three among six psoriasis patients showed an increase in MED compared with the vehicle-treated site. These findings imply that calcipotriol may be photoprotective and that more extensive studies with various doses of UV irradiation and modes of calcipotriol delivery are required.     

Topical isoflavones provide effective photoprotection to skin

Background/purpose: Isoflavones, one main group of phytoestrogens, have antioxidative and photoprotective effects in cellular and mouse studies. The aim of this study is to obtain a more comprehensive understanding of the isoflavone‐mediated photoprotection with the pig skin model, a more human‐resembling model. Methods: The pig skin was treated with five well‐known isoflavone compounds (genistein, equol, daidzein, biochanin A, and formononetin) and one antioxidant combination solution of 15% vitamin C and 1% vitamin E and 0.5% ferulic acid (CEF) daily for 4 days. Skin was irradiated with solar‐simulated UV irradiation, 1 to 5 minimal erythema dose (MED) at 1‐MED intervals. Evaluation was carried out 24 h later by colorimeter‐measured erythema and sunburn cell numbers. Results: Topical application of 0.5% solutions of three individual phytoestrogens – genistein, daidzein, biochanin A – are better than similar solutions of equol or formononetin in protecting pig skin from solar‐simulated ultraviolet (SSUV)‐induced photodamage, as measured by sunburn cell formation and/or erythema. However, the protection was less than that provided by a topical combination antioxidant standard containing 15% L‐ascorbic acid, 1%α‐tocopherol, and 0.5% ferulic acid. Conclusion: Isoflavones provide effective photoprotection and are good candidate ingredients for protection against ultraviolet (UV) photodamage.     

Botanical antioxidants in the prevention of photocarcinogenesis and photoaging

Exposure of the skin to ultraviolet (UV) radiation, particularly its UV-B component (280-320 nm), from the sun results in erythema, edema, hyperplasia, hyperpigmentation, sunburn cells, immunosuppression, photoaging, and skin cancer. Amongst these various adverse effects of UV-B radiation, skin cancer and photoaging are of great concern. More recent changes in lifestyle have led to a significant increase in the amount of UV-B radiation people receive leading to a surge in the incidence of skin cancer and photoaging. As these trends are likely to continue in the foreseeable future, the adverse effect of UV-B has become a major human health concern. Therefore, development of novel strategies to reduce the occurrence of skin cancer and delay the process of photoaging are highly desirable goals. One approach to reduce their occurrence is through photochemoprevention, which we define as the use of agents capable of ameliorating the adverse effects of UV-B on the skin. Photochemoprevention via use of botanical antioxidants, present in the common diet of human have gained considerable attention as photochemopreventive agents for human use. Many such agents have also found a place in skin care products. This review will focus on the effects of selected botanical antioxidants in the prevention of photocarcinogenesis and photoaging.