Sophie Seité

MEXORYL SX : A BROAD ABSORPTION UVA FILTER PROTECTS HUMAN SKIN FROM THE EFFECTS OF REPEATED SUBERYTHEMAL DOSES OF UVA

There is now considerable evidence that chronic UVA exposure induces damage in animal and human skin; however, little is known about UVA protection of human skin. The aim of this study is to evaluate the efficacy of Mexoryl SX, a broad UVA absorber (lamada max = 345 nm) against UVA-induced changes in human skin. The regimen of UVA exposure (13 weeks with increasing suberythemal doses) induces intense pigmentation with no erythema. Skin hydration and elasticity decrease, whereas total skin thickness, assessed by echography, remains unchanged. Irradiated epidermis reveals a significant thickening of the stratum corneum, an absence of hyperplasia and an increase in the expression of the protective iron-storage protein ferritin. No significant alterations are seen using antisera against type IV collagen or laminin, suggesting that the dermal-epidermal junction (DEJ) is mainly preserved. In dermis, enhanced expression of tenascin is seen just below the DEJ but type I procollagen, which is localized at the same site, is unaltered. Although we are unable to visualize any changes in elastic network organization using Luna staining or specific antiserum directed against human elastin, we notice an increased deposition of lysozyme or alpha-1 antitrypsin on elastin fibres. Mexoryl SX (5%) efficiently prevents these alterations. Thus, these results suggest that UVA photoprotection can prevent early putative alterations leading to photoageing.

Alterations in human epidermal Langerhans cells by ultraviolet radiation: quantitative and morphological study

Summary Backgroundu2003Ultraviolet (UV) exposure of human skin induces local and systemic immune suppression. This phenomenon has been well documented when UVB radiation (290–320u2003nm) is used. The mechanism is thought to involve Langerhans cells (LCs), the epidermal dendritic cells that play a crucial role in antigen presentation. A variety of studies have clearly demonstrated that UVB radiation decreases LC density and alters their morphology and immunological function, but little is known about the effects of the entire UV spectrum (ultraviolet solar simulated radiation, UV‐SSR or UVBu2003+u2003UVA) or UVA (320–400u2003nm) radiation alone.

A full-UV spectrum absorbing daily use cream protects human skin against biological changes occurring in photoaging

Background: There is overwhelming evidence that exposure of human skin to ultraviolet radiations (UVR) leads to the development of cutaneous photoaging and eventually to neoplasia. This study was designed to evaluate in humans the protection afforded by a daily use cream containing a photostable combination of UVB and UVA absorbers (Uvinul® N539, Parsol® 1789 and Mexoryl® SX) providing a continuous absorption through the entire UV spectrum, against damages induced by repeated daily exposure to solar simulated radiation (SSR).

Acid and neutral sphingomyelinase, ceramide synthase, and acid ceramidase activities in cutaneous aging.

Abstract:u2002 In aged skin, decreased levels of stratum corneum ceramides have been described. Epidermal ceramides are generated by sphingomyelin hydrolysis or synthesis from sphingosin and fatty acids and are degraded by ceramidase. We recently showed that epidermal acid sphingomyelinase (A‐SMase) generates ceramides with structural function in the stratum corneum lipid bilayers, which provide for the permeability barrier function of the skin. Here, we examined the activities of epidermal A‐SMase, ceramide synthase, and ceramidase in chronologically aged versus young hairless mouse skin. We found reduced A‐SMase and ceramide synthase activities in the epidermis of aged mice. However, studies on enzyme localization revealed unchanged, ongoing high A‐SMase activity in the outer epidermis, which correlated with reported normal barrier function found in aged skin under basal conditions. Reduced A‐SMase and ceramide synthase activity was noted in the inner epidermis, correlating with reduced capacity for permeability barrier repair in aging. Ceramidase activity was not age dependent. In summary, we found reduced activities of ceramide‐generating SMase and ceramide synthase in the inner epidermis of aged skin, explaining its reduced capacity in barrier repair. In contrast, A‐SMase activity in the outer epidermis was unchanged, indicating that this enzyme is crucially involved in basal permeability barrier homeostasis.

Accumulated p53 protein and UVA protection level of sunscreens

Nuclear p53 expression is a sensitive parameter for the detection of ultraviolet (UV)‐induced skin damage, and it has been used as an endpoint to evaluate the effectiveness of sunscreens. In this study, we compared the protection provided by two sunscreens having identical sun protection factors (SPF) but different UVA protection factors (UVA‐PF) measured by the persistent pigment darkening method (PPD). The SPF of the sunscreens was 7 and the UVA‐PF were respectively 7 and 3. Nuclear p53 protein was quantified in human skin biopsies treated with sunscreens and exposed 8 times to 5 MED of solar simulated radiation (SSR). The results showed that both sunscreens offered only partial protection against the increased expression of nuclear p53 protein induced by repetitive SSR exposures. However, a significantly lower level of p53‐positive cells was found in areas protected with the sunscreen having the higher UVA‐PF compared to the other sunscreen protected areas. In order to verify whether the difference in efficacy of these products was due to the difference in UVA absorption capacity, we quantified epidermal p53 protein accumulation after 8 exposures to either UVA (320–400 nm) or UVA1 (340–400 nm). We showed that as with SSR, repetitive exposures to 12.5 and 25 J/cm2 of UVA or UVA1 induced a significant increase in p53‐positive cells in the human epidermis. These results confirmed that SPF determined on the basis of an acute erythemal reaction does not predict the level of protection against cumulative damage. They also showed that the protection provided by two sunscreens with different UVA protection factors is different (based on nuclear p53 protein accumulation), and that the PPD method can distinguish varying levels of sunscreen efficacy against UVA‐induced cell damage.

The benefit of daily photoprotection

BACKGROUNDnIt is now recognized that both ultraviolet (UV)-A and UVB wavelengths participate in the generation of photodamaged human skin during sun exposure. During usual daily activities, an appropriate protection against solar UV exposure should prevent clinical, cellular, and molecular changes potentially leading to photoaging.nnnOBJECTIVEnThis study was designed to evaluate in human beings the protection afforded by a day cream containing a photostable combination of UVB and UVA filters and thus protect against the UV-induced skin alterations.nnnRESULTSnIn solar-simulated radiation exposed and unprotected skin sites we observed melanization. The epidermis revealed a significant increase in stratum corneum and stratum granulosum thickness. In the dermis, an enhanced expression of tenascin and a reduced expression of type I procollagen were evidenced just below the dermoepidermal junction. Although no change in elastic fibers in exposed buttock skin was seen, a slightly increased deposit of lysozyme and alpha-1 antitrypsin on elastin fibers was observed using immunofluorescence techniques. A day cream with photoprotection properties was shown to prevent all of the above-described alterations.nnnLIMITATIONSnThis study was performed on a limited number of patients (n = 12) with specific characteristics (20-35 years old and skin type II and III). Two dermal alterations were evaluated by visual assessment and not by computer-assisted image analysis quantification.nnnCONCLUSIONnOur in vivo results demonstrate the benefits of daily photoprotection using a day cream containing appropriate broad-spectrum sunscreens, which prevent solar UV-induced skin damages.

Protection of skin biological targets by different types of sunscreens

In vitro and in vivo studies provide a body of evidence that adequate protection of the skin against ultraviolet (UV)‐induced damage requires photostable broad‐spectrum sunscreens with a proper level of UVA protection. UVA alone and UV solar simulated radiation (SSR) induce DNA lesions in keratinocytes and melanocytes as reflected by the comet assay and p53 accumulation. UVA and SSR impair the immune system as shown by significant alteration of Langerhans cells and inhibition of contact hypersensitivity response to chemical allergens and delayed‐type hypersensitivity response to recall antigens. Any of these detrimental effects is more efficiently prevented by sunscreens with a higher level of protection in the UVA range. The involvement of UVA (fibroblast alteration, increased metalloproteinase expression) and the pivotal need for well‐balanced UVA/UVB sunscreens were further demonstrated using reconstructed three‐dimensional skin models.

Chronic UVB- and all-trans retinoic-acid-induced qualitative and quantitative changes in hairless mouse skin

Histochemical and ultrastructural studies have already demonstrated that chronic exposure to UV radiation induces profound alterations in all structural elements of the skin and that topical all-trans retinoic acid (tRA) can substantially correct much of the tissue damage. However, previous biochemical studies on dermal components of the extracellular matrix have led to contradictory results, particularly with regard to the effect of chronic UV exposure. The aim of our study was to investigate changes in collagen content and other dermal modifications induced by tRA in irradiated and non-irradiated hairless mouse skin. Hairless mice were exposed to increasing doses of UVB for 10 weeks (the cumulative total dose was 4.6 J cm-2). After the UV irradiation period the animals were treated with 0.05% tRA or with ethanol-polyethylene glycol vehicle alone three times a week for up to 10 weeks. Non-irradiated animals underwent the same treatments. The main clinical and histological changes induced by UVB exposure were erythema, wrinkling, keratosis and epidermal thickening. Following UVB exposure, tRA treatment did not improve the clinical aspect but increased the width of the dermal repair zone. Fibronectin, laminin and type I and VI collagens were detected by indirect immunofluorescence techniques in this zone. Type I and III collagens were quantitated in skin fragments after cyanogen bromide digestion and polyacrylamide gel electrophoresis. Under our experimental conditions, UVB irradiation alone induced neither changes in total collagen nor in type I and III collagen levels. tRA treatment of irradiated skin significantly increased both type I and III collagen levels by factors of 1.33 and 1.88 respectively. The ratio of type III to types I + III increased significantly. Topical tRA also increased collagen type levels in non-irradiated hairless mouse skin. Type I collagen increased proportionally to type III. This study leads to the conclusion that topical tRA exerts direct or indirect effects on collagen metabolism in irradiated as well as non-irradiated hairless mouse skin.

Biological effects of simulated ultraviolet daylight: a new approach to investigate daily photoprotection

Background: The irradiance of standard ultraviolet daylight (UV‐DL) is representative of most frequently encountered UV exposure conditions and simulators of UV‐DL can now be used to properly investigate the biological effects of a non‐extreme UV radiation. One of the characteristics of the simulated UV‐DL used in this study is its dUVA to dUVB irradiance ratio, which amounts to 24, instead of close to 10, for the simulated zenithal UV radiation (UV‐SSR).

P53 MUTATIONS IN CUTANEOUS LESIONS INDUCED IN THE HAIRLESS MOUSE BY A SOLAR ULTRAVIOLET LIGHT SIMULATOR

We investigated skin lesions induced in hairless SKH:HR1 mice by chronic exposure to a solar ultraviolet light (UV) simulator for alterations of the p53 gene in conserved domains. Mutations of exons 5–8 of the p53 gene in skin lesions were screened in 31 benign skin lesions (hyperplasias), 25 precancerous skin lesions (keratoacanthomas), and 25 malignant skin lesions (squamous cell carcinomas; SCC) by polymerase chain reaction–single‐strand conformation polymorphism analysis. Most of the mutations occurred at dipyrimidine sequences located on the nontranscribed strand; the most frequent modifications were C→T transitions (77%) and CC→TT tandem mutations (5%); the latter are considered the UV fingerprint. p53 mutations were detected in 3% of the hyperplasias, 12% of the keratoacanthomas, and 52% of the SCCs. Hence, the high frequency of p53 mutations in SCCs compared with keratoacanthomas induced by a solar UV simulator suggested that, in our study, p53 mutations probably occurred as a late event in the skin carcinogenesis progression of SCC. Interestingly, the level of CC→TT tandem mutations in the SCCs (5%) was similar to that found in SCCs induced in hairless mice by UVB alone. p53 protein was also detected in the different types of skin lesions by immunohistochemical analysis. Thus, our data from hairless mouse skin tumors induced by a solar UV simulator confirmed the major role of UVB‐induced DNA damage in skin carcinogenesis and suggested that UVA plays a minor role in bringing about p53 alterations. Mol. Carcinog. 22:167–174, 1998.