Cutaneous solar ultraviolet exposure and clinical aspects of photodamage

Solar ultraviolet (UV) radiation reaching the earth is a combination of UVB (290-320 nm) and UVA (320-400 nm) wavelengths. Since UVA is less energetic than UVB, UVB has long been thought to be the factor responsible for the damaging effects of solar radiation. But with modern tools such as in vitro models, it has been proven that UVA plays a major role. The objective of this review is to show how skin may be exposed to UV light and to highlight the clinical aspects of UV-induced skin damages with the respective contribution of UVB or UVA. Even if UVA is less energetic than UVB, it is more abundant and penetrates deeper into the skin, reaching as far as the dermis. Various factors also influence skin exposure to UV light: the latitude, season, and time of the day. Acute as well as chronic sun exposure induces short- and long-term clinical damages. Erythema and pigmentation are immediate responses of normal human skin exposed to UV radiation. The long-term effects are photoaging and photocarcinogenesis. In particular, UVA appears to play a major role in the deterioration of dermal structure leading to the photoaged appearance of the skin.     

Photoprotection: a Review of the Current and Future Technologies

Exposure to ultraviolet (UV) radiation is associated with a variety of harmful effects ranging from photoaging to skin cancer. UVB (290 to 320 nm) directly damages the cellular DNA leading to the formation of the 6-4 cyclobutane pyrimidine dimmers, and UVA (320 to 400 nm) indirectly damages the DNA via the production of oxygen radical species. In this review, we focused on the technological and scientific aspects of photoprotection using sunglasses and clothing while attempting to dispel some of the misconceptions. In addition to the basic knowledge relating to sunscreens, we reviewed the current guidelines for testing and labeling UVA protection around the world, controversies associated with nanoparticles, and future sunscreens actives waiting for the Food and Drug Administration approval. Lastly, we reviewed alternative agents, such as antioxidants, that can be used to supplement and augment photoprotection provided by sunscreens.     

The sun protection factor (SPF) inadequately defines broad spectrum photoprotection: demonstration using skin reconstructed in vitro exposed to UVA,UVBor UV-solar simulated radiation

Wavelength specific biological damage has been previously identified in human skin reconstructed in vitro. Sunburn cell and pyrimidine dimers were found after UVB exposure, and alterations of dermal fibroblasts after UVA exposure. These damages permitted us to discriminate UVB and UVA single absorbers. The present study shows that these biological effects can be obtained simultaneously by a combined UVB + UVA exposure using ultraviolet solar simulated light (UV-SSR), which represents a relevant UV source. In addition, the protection afforded by two broad spectrum sunscreen complex formulations was assessed after topical application. These two formulations displayed the same sun protection factor but different UVA protection factors determined by the persistent pigment darkening (PPD) method. Dose response experiments of UVA or UV-SSR showed that the preparation with the highest PF-UVA provided a better protection with regard to dermal damage compared to the other formulation. Using an original UVB source to obtain the UVB portion of SSR spectrum, the preparations provided the same protection. This study strikingly illustrates the fact that the photoprotection afforded by two sunscreen formulations having similar SPF values is not equal with regard to dermal damage related to photoaging.     

Photoprotection of human skin beyond ultraviolet radiation

Photoprotection of human skin by means of sunscreens or daily skin‐care products is traditionally centered around the prevention of acute (e.g. sunburn) and chronic (e.g. skin cancer and photoaging) skin damage that may result from exposure to ultraviolet rays (UVB and UVA). Within the last decade, however, it has been appreciated that wavelengths beyond the ultraviolet spectrum, in particular visible light and infrared radiation, contribute to skin damage in general and photoaging of human skin in particular. As a consequence, attempts have been made to develop skin care/sunscreen products that not only protect against UVB or UVA radiation but provide photoprotection against visible light and infrared radiation as well. In this article, we will briefly review the current knowledge about the mechanisms responsible for visible light/infrared radiation‐induced skin damage and then, based on this information, discuss strategies that have been successfully used or may be employed in the future to achieve photoprotection of human skin beyond ultraviolet radiation. In this regard we will particularly focus on the use of topical antioxidants and the challenges that result from the task of showing their efficacy.     

防晒霜的应用和评价

局部应用防晒霜越来越被公众接受。大部分的防晒霜由物理防晒剂和化学防晒剂组成．可以有效地防止紫外线引起的皮肤红斑反应、免疫抑制、光老化以及皮肤癌的发生。防晒霜应有中波紫外线和长波紫外线的全面防护功能。评价防晒霜要从其吸收光谱，衰减系数，中波紫外线防护功能以及长波紫外线防护功能等方面进行考虑。     

Photodamage to human skin by suberythemal exposure to solar ultraviolet radiation can be attenuated by sunscreens: a review

The effects of acute or repeated suberythemal solar ultraviolet radiation (UVR) exposure on human skin have been insufficiently investigated. Such exposure almost certainly has important long-term consequences that include skin ageing and skin cancer. This review summarizes the published data on the biological effects of suberythemal exposure using a wide range of clinical, cellular and molecular endpoints, some of which may be considered as biomarkers for skin cancer and photoageing. We also include some recent unpublished results from our laboratories. The effects of UVA (320-400 nm), UVB (290-320 nm) and total solar UVR (290-400 nm) are compared. We demonstrate that avoiding sunburn does not prevent many indicators of cutaneous biological damage and that use of low sun protection factor (SPF) sunscreen can inhibit much of the damages induced by suberythemal exposure to UVR. However, even when applied correctly, sunscreen use will result in suberythemal exposure. The degree and spectral quality of such exposure will depend on the SPF and absorption spectrum of the sunscreen, but nonetheless it may contribute to cumulative photodamage. This review may help to determine the level of photoprotection required in sunscreens and daily use products, as well as the ideal ratio of UVB/UVA protection, to improve long-term photoprotection outcomes.     

Sun protection and sunscreen labeling--an update

Sun exposure is today well recognized as having an adverse effect on human skin. Part of sun radiation, ultraviolet radiation A (UVA) and B (UVB), can modify skin structures and induce short-term skin changes (sunburn, tanning, hyperkeratinization, brown spots) and long-term skin damages (accelerated skin aging and skin cancers). Protection against both UVA and UVB is very important, therefore sun protection by clothes, avoiding sun exposure and correct use of sunscreens are important means to reduce short- and long-term solar radiation effects. The recommendation of appropriate sunscreen by doctors and cosmetic professionals (the function of skin type and sun radiation intensity) is today easier due to the recently implemented European uniform labeling system of sunscreens and detailed information for consumers.     

Synergistic effects of long‐wavelength ultraviolet A1 and visible light on pigmentation and erythema

Ultraviolet (UV) radiations from sunlight that reach the surface of the earth are categorized as UVB (wavelength range 280–320 nm) and UVA (320–400 nm). The UVA is further divided into UVA2 (320–340 nm) and UVA1 (340–400 nm). In the United States and other nations, rules have been set outlining how products that are designed to protect against UVB and UVA should be tested, and there are also strict rules about how these products can be labeled. The SPF (sun protection factor) mainly shows the level of protection against UVB only, and SPF along with “Broad Spectrum” on a label shows protection against both UVB and UVA. The criteria that decide whether or not manufacturers can claim a product gives broad spectrum protection, in the US, primarily focus on protection offered below 370 nm. Visible light (VL), which ranges from 400 nm to 700 nm, is a spectrum of wavelengths that are visible to the human eye. To date, only the UV part of sunlight, which is not visible light, has been considered to cause photodamage (damage caused by sunlight) resulting in skin cancers and photoaging (skin ageing due to the sun). The visible part of the sunlight was considered relatively harmless. This study, from the US, investigated skin responses, in terms of sunburn and tanning, caused by visible light in combination with the tail end of long wavelength UVA1 (referred to as VL+UVA1, 370–700 nm) and compared them to those caused by pure visible light (400–700 nm). The findings of the study show that skin responses, in terms of pigmentation (colouring/tanning) and erythema (redness/sunburn), resulting from VL+UVA1 were stronger than those induced by pure visible light alone. This implies that wavelengths that current broad spectrum sunscreens do not cover can affect pigmentation and erythema. These wavelengths may have a role in conditions aggravated by sun exposure such as melasma and post‐inflammatory hyperpigmentation, especially in patients with skin of color. The development of prodcts that protect against visible light and long wavelength UVA1 will be helpful for these, as well as for the management of certain skin disorders triggered by UVA1 and VL.     

Irradiation of skin with visible light induces reactive oxygen species and matrix-degrading enzymes

Daily skin exposure to solar radiation causes cells to produce reactive oxygen species (ROS), which are a primary factor in skin damage. Although the contribution of the UV component to skin damage has been established, few studies have examined the effects of non-UV solar radiation on skin physiology. Solar radiation comprises <10% of UV, and thus the purpose of this study was to examine the physiological response of skin to visible light (400-700 nm). Irradiation of human skin equivalents with visible light induced production of ROS, proinflammatory cytokines, and matrix metalloproteinase (MMP)-1 expression. Commercially available sunscreens were found to have minimal effects on reducing visible light-induced ROS, suggesting that UVA/UVB sunscreens do not protect the skin from visible light-induced responses. Using clinical models to assess the generation of free radicals from oxidative stress, higher levels of free radical activity were found after visible light exposure. Pretreatment with a photostable UVA/UVB sunscreen containing an antioxidant combination significantly reduced the production of ROS, cytokines, and MMP expression in vitro, and decreased oxidative stress in human subjects after visible light irradiation. Taken together, these findings suggest that other portions of the solar spectrum aside from UV, particularly visible light, may also contribute to signs of premature photoaging in skin.     

Update on sunscreens

Sunscreens have been around for more than 70 years. Designed originally to protect against sunburn, recognition of the various harmful effects of ultraviolet (UV) radiation has broadened the use of sunscreens. The addition of effective UVA sunscreen agents has enabled claims beyond protection against sunburn to include prevention of idiopathic photodermatosis, actinic keratoses, skin cancer, and photoaging. This article will review some of the recent advances in photoprotection, including the development of sunscreen formulations offering higher and broader protection against solar radiation.     

Prevention of ultraviolet-induced skin pigmentation

BACKGROUND/PURPOSE: Exposure to ultraviolet (UV) radiation increases skin pigmentation and usually results in an even darkening of the skin. However, it may also occasionally lead to the development of hyperpigmented lesions due to a local overproduction of pigment. Skin pigmentation is induced both by UVB and UVA rays. METHODS: The in vivo protection by sunscreens against pigmentation was studied using the determination of a level of protection against pigmentation based on the standardized sun protection factor (SPF) test method. The method includes delayed UVB and UVA pigmentations. The level of prevention against pigmentation was determined 7 days after exposure to solar-simulated radiation by visual assessment. It was calculated using the ratio of the minimal pigmenting dose on protected skin to the minimal pigmenting dose on unprotected skin. Broadspectrum UVB/UVA filters, Mexoryl SX and Mexoryl XL, and complete formula were tested. RESULTS: Protection against pigmentation correlates with the concentration of Mexoryl SX. The levels of protection obtained show a synergetic effect of Mexoryl SX when associated with Mexoryl XL. When different products having the same SPF (same protection against erythema) and different levels of UVA protection are compared, only sunscreen products with a high level of UVA protection show a similar level of protection against sunburn and pigmentation. Products with low UVA protection have a lower capacity of preventing induced pigmentation compared with their efficacy against erythema. CONCLUSIONS: These studies have evidenced that SPF determination was not sufficient to account for the efficiency in preventing pigmentation and that UVA protection was an essential part of this prevention.     

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.     

Effects of UVA radiation on an established immune response in humans and sunscreen efficacy

Abstract: It is well established that ultraviolet radiation has immunomodulatory effects which may be involved in skin cancer. Recent studies have shown that UVA radiation (320–400 nm) as well as UVB (290–320 nm) is immunosuppressive. This means that sunscreens which mainly absorb UVB (protection against erythema) may be less effective in preventing UVR-induced immunosuppression than broad-spectrum products. We have studied the effects of UVA exposure on the human delayed-type hypersensitivity response (DTH) and compared the efficacy of sunscreens having different levels of UVA protection under both solar-simulated radiation (SSR) chronic exposures or acute exposure and outdoor real-life solar exposure conditions. DTH was assessed using recall antigens. Our studies clearly demonstrate the role of UVA in the induction of photoimmunosuppression together with the need for sunscreen products providing efficient photoprotection throughout the entire UV spectrum. These data suggest that sun protection factor may not be sufficient to predict the ability of sunscreens for protection from UV-induced immune suppression. Determining the level of UVA protection is particularly necessary, because UVA seems to have a relatively low contribution to erythema but is highly involved in immunosuppression.     

The development of efficient sunscreens

Skin exposure to acute or repetitive ultraviolet light induces risks which are now well identified. An efficient photoprotection is thus required for both UVB and UVA radiation. In particular, increasing evidence of the detrimental effects of UVA on skin has led to the development of a new generation of sunscreens that provide effective protection throughout the whole UV radiation spectrum. Many new UV filters have been introduced in the last decade, particularly UVA filters, with improved efficacy and safety. Sunscreen filters must be carefully combined to achieve esthetically pleasing products offering photostable and well-balanced photoprotection.     

A review of inorganic UV filters zinc oxide and titanium dioxide

Photoprotection has become integral in the prevention of keratinocyte cancer and photoaging. Organic ultraviolet (UV) filters such as oxybenzone and octinoxate have become controversial due to their potential impact on the environmental and their potential human health risks. As such, inorganic UV filters, zinc oxide (ZnO) and titanium dioxide (TiO₂)_, have become paramount in discussions about photoprotection. ZnO and TiO₂ are used in sunscreens as nanoparticles, which denotes a size <100 nm. The smaller size of these mineral particles increases their cosmetic acceptability by users as they are much less visible after application. ZnO has a broad UVA‐UVB absorption curve, while TiO₂ provides better UVB protection. Overall, the human health risks with inorganic filters are extremely low given a lack of percutaneous absorption; however, there is potential risk when exposed via inhalation, prompting recommendations against spray sunscreen products with nanoparticles. At this time, the known risk to the environment is low though the risk stratification may evolve with increasing usage of these filters and higher environmental concentrations. The continued practice of photoprotection is critical. The public should be counseled to seek shade, use photoprotective clothing including hats and glasses in addition to sunscreens on sun‐exposed skin. For those concerned about emerging evidence of environmental impact of organic UV filters, based on current evidence, ZnO and TiO₂‐containing sunscreens are safe alternatives.     

Sunburn cell formation, dendritic cell migration, and immunomodulatory factor production after solar-simulated irradiation of sunscreen-treated human skin explants in vitro

Using human skin explants, we investigated the effects of two different sunscreen preparations containing a chemical UVB filter alone [sun protection factor (SPF) 5.2] or UVA+UVB filter [SPF 6.2] on sunburn cell formation, dendritic cell (DC) migration, CD86- and CD1a-positive cell number, and tumor necrosis factor alpha (TNFalpha) and interleukin (IL)-1, IL-10, and IL-12 production in the skin after irradiation with different doses of solar-simulated UV radiation. Sunscreen- or placebo-treated skin explants were irradiated with solar-simulated UV radiation at 0.5, 1, and 2 minimal erythematous dose equivalents (MEDE) (as determined in an in vivo human study) multiplied by the SPF of the placebo or sunscreens. After irradiation, skin explants were floated on RMPI medium for 48 h. Cells that had emigrated and the skin explants were histologically analyzed, and the soluble mediators were measured in the supernatants by ELISA. Exposure to UV radiation led to concentration-dependent increases in sunburn cell formation and TNFalpha production but a concentration-dependent decrease in DC migration and CD86- and CD1a-positive cell number in the epidermis. Both chemical sunscreens protected against those alterations. The immunoprotective capacity of the sunscreens correlated with their SPF but was independent of the sunscreens' UVA protection capacity, suggesting that UVA is not a major factor for immunosuppression under the conditions used in the model. UV irradiation did not significantly affect the vitality of emigrated DC; the expression of HLA, CD80, and lag on emigrated cells; the number of CD1a-positive cells in the dermis; or the production of IL-1, IL-10, and IL-12. We conclude that our model may be useful in determining the immunoprotective capacity of sunscreens.     

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.     

Evaluating the UVA photoprotection of sunscreens with murine skin edema.

The acute and chronic deleterious effects of UVA on skin have prompted a growing interest in developing effective UVA-photoprotective sunscreens. The quantification of their UVA photoprotection remains, however, a major problem. In the present study, murine skin edema induced by 8-methoxypsoralen plus UVA (PUVA) is evaluated as a screening method for quantifying the UVA photoprotection of commercially available sunscreens. The PUVA-induced murine skin edema is provoked on the dorsa of female hairless albino mice and measured with a hand-held micrometer. A clear time course and a well-defined dose-response relationship are demonstrated. Therefore, a UVA-photoprotection factor (UVA-PF) could be defined by dividing the minimal edema dose with sunscreen by the minimal edema dose without sunscreen. The UVA-PF values obtained with this method were quantitatively and qualitatively very similar to those obtained in 8-methoxypsoralen-photosensitized murine skin by using the number of sunburn cells as the biologic end point and were qualitatively similar to UVA-PF values obtained in human skin using phototoxic erythema and UVASUN-induced tanning as the parameter. It is concluded that PUVA-induced murine skin edema offers an objective, reproducible, and easily applicable screening method for quantifying the degree of UVA photoprotection of a sunscreen.     

Sunscreens containing the broad-spectrum UVA absorber, Mexoryl SX, prevent the cutaneous detrimental effects of UV exposure: a review of clinical study results

Background: UVA exposure of human skin mainly produces reactive oxygen species (ROS) leading to DNA, cell and tissue damage. It alters immune function, pigmentation and it is certainly responsible for a large part of photoaging changes. Moreover UVA is implicated in the etiology of several photodermatoses. As a consequence, to provide adequate protection, sunscreens or skin care products for daily use protective products need UVA absorbers combined with UVB ones. Aim: To assess the efficacy of sunscreens containing a broad‐spectrum UVA absorber the Mexoryl^® SX or ecamsule and to compare formulations with and without it through a large number of clinical studies in human volunteers and patients. Methods: The following assessments were conducted:

• ? Prevention of excessive pigmentation induced by UV exposure in Caucasian and Asian skins using a method that measures pigmentation protection factors (PPF).
• ? Efficacy against DNA damage by measurement of pyrimidine dimer formation and p53 protein accumulation.
• ? Protection of immune system using delayed type hypersensitivity (DTH) reactions to recall antigens, isomerization of urocanic acid (UCA), alteration of Langerhans cells (LC) density, morphology and function.
• ? Reduction of epidermal and dermal alterations induced by repeated UVA or UV solar simulated radiation (SSR) using histology or immunohistology.
• ? Prevention of the polymorphous light eruption (PMLE) in patients prone to develop this disease.

Results: Mexoryl^® SX‐containing formulations showed a dose‐dependent level of protection against pigmentation. For a same sun protection factor (SPF) the higher the UVA protection was, the higher was the PPF. Pyrimidine dimer formation and p53 accumulation were significantly reduced by formulations with Mexoryl^® SX. In the studies looking at the suppression of DTH reactions to recall antigens by the different UV spectra, the LC alterations and the cis UCA formation, Mexoryl^® SX formulations always showed a higher protective potency than sunscreen without it even when the protection against erythema was similar (products with same SPF). Mexoryl^® SX formulations also prevented or significantly decreased to minimal, ferritin, tenascin and lysozyme expression induced by repeated UVA or SSR exposure. It also reduced the enhancement of collagenase 2 mRNA expression induced by SSR exposure. Finally PMLE study demonstrated that UVA protection was essential for the prevention of this photodermatose. Conclusion: Mexoryl^® SX formulated in sunscreens or daily use products have been shown to be an effective UV absorber, leading to an increased efficacy of these products against a large number of biological damage induced by UVA, SSR or sun exposure.     

Influence of corticosteroids on ultraviolet light erythema and pigmentation in man

Summary Topical hydrocortisone and betamethasone-17-valerate were tested in alcoholic solution in human skin for their influence on a developing ultraviolet light erythema. Although the normal response was augmented by the ethanol vehicle, both drugs, applied before exposure, inhibited the erythema induced by irradiation of the sunburn range (UVB). They did not inhibit a phototoxic erythema induced by 8-methoxy-psoralen and long-wave irradiation (UVA). The pigmentation caused by the UVA exposure also appeared after UV stimulation which was too weak to evoke erythema.

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Zusammenfassung Auf die Haut aufgelegte alkoholische Lösungen von Hydrokortisonacetat und Betamethason-17-valerat wurden wegen einer eventuellen Einwirkung auf das ultraviolette Erythem in homo untersucht. Beide Substanzen, vor der Lichtexposition aufgetragen, zeigten eine Hemmung des Sonnenbranderythems (UVB). Ein phototoxisches Erythem, ausgelöst durch 8-Methoxypsoralen und langwellige UV-Strahlung (UVA) wurde dagegen nicht beeinflußt. Die Pigmentierung im UVA-Versuch war auch bei kurzen UV-Belichtungen, die kein Erythem hervorriefen, deutlich.