Protection against long ultraviolet and/or visible light with topical dihydroxyacetone. Implications for the mechanism of action of the sunscreen combination, dihydroxyacetone/naphthoquinone.

Dihydroxyacetone (DHA) chemically induces long ultraviolet (UV) and/or visible photoprotection into the stratum corneum as demonstrated by (a) long UV protection of albino rats which were psoralen-photosensitized to black fluorescent light and (b) sunlight protection of five patients with long UV and/or visible photosensitivity. Previously, DHA treatment of skin was considered to provide no protection against UV. For clinical use, the combination of DHA and lawsone (2-hydroxy-1,4-naphthoquinone) is preferred to DHA alone, because it provides rapid, positive protection over a range extending from short UV into the visible region of sunlight.     

Protection from photodamage by topical application of caffeine after ultraviolet irradiation

BACKGROUND: Characterization of mechanisms that can reverse residual damage from prior skin exposure to ultraviolet (UV) would be of considerable biological and therapeutic interest. Topical caffeine application to mouse skin that had previously been treated with UV has been shown to inhibit the subsequent development of squamous cell carcinomas. OBJECTIVES: We used an established mouse photodamage model to investigate other possible effects of topical caffeine application after UV. METHODS: SKH-1 hairless mice were treated with ultraviolet B (UVB) followed immediately by topical application of caffeine or vehicle three times weekly for 11 weeks. RESULTS: Caffeine applied topically after UV treatment resulted in a significant decrease in UV-induced skin roughness/transverse rhytides as assessed by treatment-blinded examiners. Histologically, topical caffeine application after a single dose of UVB more than doubled the number of apoptotic keratinocytes as evaluated by sunburn cell formation, caspase 3 cleavage and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labelling (TUNEL) staining. A trend towards decreased solar elastosis was noted in the caffeine-treated group although this was not statistically significant. Other histological parameters including epidermal hyperplasia, solar elastosis and angiogenesis were increased in mice treated with UV but topical application of caffeine did not alter these particular UV effects. CONCLUSIONS: These findings support the concept that topical application of caffeine to mouse skin after UV irradiation promotes the deletion of DNA-damaged keratinocytes and may partially diminish photodamage as well as photocarcinogenesis.     

Efficacy of a sunscreen containing butyl methoxydibenzoylmethane against ultraviolet A radiation in photosensitized subjects

Topical formulations containing a new chemical entity, the ultraviolet A absorber Parsol 1789 (butyl methoxydibenzoylmethane), were evaluated as agents for protecting human skin against ultraviolet A (UVA) radiation. Healthy subjects were photosensitized to UVA radiation by ingestion of 8-methoxypsoralen (0.6 mg/kg). After 90 minutes, five formulations (vehicle, vehicle + butyl methoxydibenzoylmethane, vehicle + butyl methoxydibenzoylmethane + padimate O, vehicle + padimate O, and a marketed sunscreen containing padimate O, oxybenzone, and octyl salicylate) were applied in a randomized, double-blind manner to areas on the lower part of the back. Thirty minutes later, sites in the five treated areas and in a sixth unprotected area were exposed to graduated doses of UVA radiation. Test sites were evaluated for erythema 48 and 72 hours after UVA exposure, and for melanogenesis approximately 2 weeks later. The combination of butyl methoxydibenzoylmethane + padimate O demonstrated significantly greater protection than the combination of padimate O, oxybenzone, and octyl salicylate.     

Effects of long wave ultraviolet radiation on photosensitizing and related compounds. I

The effects of long ultraviolet radiation (UVA) on the fluorescence of twenty-four photosensitizing and related compounds were studied. Each compound was applied in two areas on the skin of hairless mice. One area was irradiated. The fluorescence in both areas was then inspected every day until it disappeared. Persistence and change of colour of the fluorescence as a direct immediate effect of UVA radiation on compounds having photoallergic potential, i.e. salicylanilide, halogenated salicylanilide and phenothiazine derivatives, was observed. Compounds known for their phototoxic effects, i.e. acridine dyes, did not show such changes after irradiation, while 8-methoxypsoralen showed persistence of fluorescence without change of colour.     

Effects of long wave ultraviolet radiation on photosensitizing and related compounds. II

The effects of long wave ultraviolet radiation (320–400 nm) on the binding of twenty-five fluorescent photosensitizing and related compounds to the major saline soluble guinea-pig epidermal proteins were studied. Binding before or after irradiation was detected on polyacrylamide disc gel electrophoresis by correlating the fluorescent migration pattern with the amido black counterstained pattern. Effects were seen only on photo-allergic and structurally related compounds (phenothiazines and halogenated salicylanilides). The binding of five phenothiazine derivatives was detected only after irradiation. Ten of twelve halogenated salicylanilides were bound without irradiation, and eleven were bound following it. Ultraviolet exposure appeared to increase the amount of each halogenated salicylanilide that was bound and/or to alter the existing complex.     

Protection against ultraviolet radiation by commercial summer clothing: need for standardised testing and labelling

Background  

The use of clothing as a means of sun protection has been recommended in recent education campaigns. Contrary to popular opinion, however, some fabrics provide insufficient ultraviolet (UV) protection.     

Characterization of cutaneous phototoxicity induced by topical alpha-terthienyl and ultraviolet A radiation

Alpha-terthienyl (alpha-T), a phototoxic thiophene compound isolated from marigolds (Tagetes species), affects cell membranes and does not appear to induce cytogenetic damage. This study was undertaken to investigate topical delivery of alpha-T and characterize its cutaneous phototoxicity in combination with long-wave UV radiation (UVA) in comparison with locally (intradermal) administered alpha-T. Percutaneous penetration (PC) of 0.1% and 1% alpha-T in a 3% Azone gel vehicle was studied in guinea pig skin in vitro and quantitated by UV fluorescence microscopy. Dose-dependent PC of epidermis, adnexae, and superficial dermis was demonstrated in vitro. Alpha-terthienyl (0.1% and 1%) in this vehicle was applied topically in vivo and irradiated with 30 J/cm2 UVA at intervals of 10 min-24 h. Maximum sensitization was achieved with irradiation 1 h following drug application. The clinical response was dose-dependent consisting of erythema, edema, crusting, erosion, and inhibition of hair growth and was observed 72 h to 7 days postirradiation. A comparable dose-dependent phototoxic response was observed when 5-500 micrograms alpha-T were injected intradermally and irradiated with UVA. These results indicated that low-dose topical alpha-T in a nonirritating vehicle can rapidly produce cutaneous photosensitization. Topical alpha-T/UVA may provide a selective and safer alternative approach for the photochemotherapy of psoriasis and other cutaneous diseases.     

An animal model for evaluation of topical photoprotection against ultraviolet A (320-380 nm) radiation

Recent studies reporting UVA (ultraviolet A radiation 320-380 nm) as an integral part of the cumulative sun-induced damage in human skin have prompted an interest in developing effective UVA photoprotective agents. The development of such compounds has been impeded by the absence of a clinically relevant animal model for evaluating their efficacy. This report describes the development and use of such a laboratory animal system. Selected concentrations of oxybenzone (2-hydroxy-4-methoxybenzophenone) in vehicle (0.1% to 6%) or vehicle alone were applied to the depilated dorsal skin of 30 Hartley strain female albino guinea pigs. The skin was irradiated with solar simulated UVA from a xenon light source. Acute radiation-induced damage was assayed by erythema grading and inhibition of [3H]thymidine incorporation into epidermal DNA. Data from erythema grading studies indicated that a significant degree of photoprotection was achieved with 6%, 3%, and 1% solutions of benzophenone compared with the control vehicle; the 6% solution was significantly more photoprotective than the 3% and 1% solutions. A 6% solution afforded significant photoprotection when assayed by [3H]thymidine incorporation.     

Ultraviolet radiation suppresses mouse-ear edema induced by topical application of arachidonic acid

Summary The effect of ultraviolet (UV) radiation on arachidonic acid (AA) cascade was examined using an in vivo model. Mouse ear lobes were painted with 1 mg AA, and the maximum response of ear swelling was measured 1 h after challenge. Arachidonic-acid-induced ear swelling was significantly suppressed by preexposure to topical psoralen plus noninflammatory doses of long-wave UV radiation (PUVA) or middle-wave UV (UVB) radiation. Ultraviolet radiation may interfere with AA pathways to suppress ear swelling since AA-induced ear swelling is considered to be mediated by metabolites derived from exogenous AA. The results may relate to the therapeutic mechanisms of UV radiation in psoriasis in which the eicosanoid cascade is involved.     

中药外搽加局部紫外线照射治疗斑秃等秃发67例疗效观察

我们自1978年3月始,试用中药外搽加局部紫外线照射治疗61例各型斑秃等,收到了满意的疗效,现报告如下.     

Protection by ultraviolet A and B sunscreens against in situ dipyrimidine photolesions in human epidermis is comparable to protection against sunburn

Sunscreens prevent sunburn and may also prevent skin cancer by protecting from ultraviolet-induced DNA damage. We assessed the ability of two sunscreens, with different spectral profiles, to inhibit DNA photodamage in human epidermis in situ. One formulation contained the established ultraviolet B filter octyl methoxycinnamate, whereas the other contained terephthalylidene dicamphor sulfonic acid, a new ultraviolet A filter. Both formulations had sun protection factors of 4 when assessed with solar simulating radiation in volunteers of skin type I/II. We tested the hypothesis that sun protection factors would indicate the level of protection against DNA photodamage. Thus, we exposed sunscreen-treated sites to four times the minimal erythema dose of solar simulating radiation, whereas vehicle and control sites were exposed to one minimal erythema dose. We used monoclonal antibodies against thymine dimers and 6-4 photoproducts and image analysis to quantify DNA damage in skin sections. A dose of four times the minimal erythema dose, with either sunscreen, resulted in comparable levels of thymine dimers and 6-4 photoproducts to one minimal erythema dose +/- vehicle, providing evidence that the DNA protection factor is comparable to the sun protection factor. The lack of difference between the sunscreens indicates similar action spectra for erythema and DNA photodamage and that erythema is a clinical surrogate for DNA photodamage that may lead to skin cancer.     

Effects of selenium compounds on induction of DNA damage by broadband ultraviolet radiation in human keratinocytes

Background Ultraviolet radiation (UVR), a ubiquitous environmental genotoxin for the skin, produces DNA damage. The trace element selenium induces synthesis of the glutathione peroxidase and thioredoxin reductase enzyme families. These selenoenzymes detoxify a range of toxic compounds generated by free radicals. Objectives To assess the effects of pretreatment of primary human keratinocytes with selenium on UVR-induced DNA damage. Methods Cells were irradiated with UVR from FS-20 lamps and were subjected to comet assay. Results Comet tail length due to UVR-induced T4 endonuclease V-sensitive sites (caused by cyclopyrimidine dimers, CPDs) increased to 35 +/- 4.5 microm (mean +/- SD) immediately after irradiation (time 0 h, 100%). After 4 h, 68% of the damage remained and after 24 h, 23% of the damage was still present. Treatment with up to 200 nmol L-1 selenomethionine or 50 nmol L-1 sodium selenite had no effect on CPD formation or rates of repair, or on the number of excision repair sites as measured by cytosine arabino furanoside and hydroxyurea treatment. However, selenite and selenomethionine protected against oxidative damage to DNA as measured by formation of formamidopyrimidine (FaPy) glycosylase-sensitive sites, which are indicative of 8-hydroxy-2-deoxyguanosine photoproduct formation. In this assay, irradiation of keratinocytes increased mean +/- SD glycosylase-specific comet tail length from 5 +/- 1.5 microm to 19 +/- 3.3 microm. Preincubation for 18 h with 50 nmol L-1 selenite abolished the UVR-induced increase in comet length. Preincubation with 200 nmol L-1 selenomethionine was similarly protective. Conclusions Selenite and selenomethionine protect keratinocytes from UVR-induced oxidative damage, but not from formation of UVR-induced excision repair sites.     

Change of ultraviolet absorbance of sunscreens by exposure to solar-simulated radiation

Regarding the outdoor behavior of the Caucasian population, modern sunscreens should provide high and broad-spectrum ultraviolet protection in the ultraviolet B as well as in the ultraviolet A range and should be photochemically stable for ultraviolet doses, which can be expected in solar radiation. At present an assessment of the photostability of suncare products is not a general requirement before marketing. In order to evaluate the photostability of suncare products we conducted an in vitro test and measured the spectral absorbance of 16 sunscreens before, and after exposure to increasing biologically weighted standard erythema doses (5, 12.5, 25, 50) of solar-simulated radiation. Seven of 16 suncare products showed a significant dose- and wavelength-dependent decrease of the ultraviolet A protective capacity, whereas the ability to absorb ultraviolet B was not affected. In the ultraviolet A range, the decrease of absorbance (photoinactivation), respectively, the increase of transmission was 12-48% for an ultraviolet exposure of 25 standard erythema dose. Photoinactivation started in the wavelength range between 320 and 335 nm with a maximum above 350 nm. Furthermore, our analysis showed that the behavior of suncare products was not predictable from its individual ingredients. Neither complex combinations of organic filters nor addition of inorganic filters could absolutely prevent photoinactivation. The inclusion of a single photounstable filter did not mean photoinstability of the complete suncare product. Photoinactivation of sunscreens appears to be an underestimated hazard to the skin, first, by formation of free radicals, second, by increased ultraviolet A transmission.     

Sister chromatid exchanges in lymphocytes of psoriatics after treatment with 8-methoxypsoralen and long wave ultraviolet radiation

Sister chromatid exchange rates in cultured cells from the blood of patients receiving photochemotherapy have been examined as an indicator of possible genetic hazards of the treatment to patients with psoriasis. Lymphocytes of untreated patients with psoriasis appear to have sister chromatid exchange rates after 72 h of culture indistinguishable from normal subjects and there is no evidence from these studies that sister chromatid exchanges are significantly increased in the lymphocytes of patients receiving photochemotherapy. Cells from blood taken from patients who had been given 8-methoxypsoralen orally 2 h before and then irradiated with UV-A in vitro were found to have an increased exchange rate which could be related to the presence of the drug in the peripheral circulation.     

Measurement of erythemal response to ultraviolet radiation by “monochromatic” photography

Summary The main early color change induced by ultraviolet light consists of a decreased oxyhemoglobin reflectance. A method is presented in which the skin together with a calibrated gray scale is photographed using an interference filter with a peak transmission at 540 nm, the region of the specific absorption bands of hemoglobin. On the processed photographs the irradiated skin can then be compared with the calibrated scale and thus the degree of ultraviolet erythema calculated.     

Cell kinetic effects of crude coal tar application plus long wave ultraviolet radiation on normal and hyperproliferative epidermis of guinea pig skin

This study investigated the cell kinetic effects of combined treatment with crude coal tar and long wave ultraviolet (UVA) radiation on the normal and n-hexadecane-induced hyperproliferative epidermis of guinea pig skin. Flow cytometry was used to determine the proportion of cells in S phase (S fraction) and G2 + M phase (G2 + M fraction). Bromodeoxyuridine incorporation was used to determine the labeling index. Conventional histologic techniques were used to observe the mitotic index. In the normal epidermis after a single treatment with tar and UVA (1 J/cm2) or tar alone, the labeling index showed an initial decrease of 4 hr duration followed by moderate increase. The initial decrease was more pronounced in the tar-UVA-treated epidermis than in the tar-treated epidermis. The mitotic index was depressed during the first 12 hr. S- and G2 + M fraction showed no changes during the first 12 to 18 hour, and then increased in varying degrees. In the hyperproliferative epidermis after two applications of tar and UVA (1 and 4J/cm2) or tar alone, the labeling index was depressed during the first 12 hr, and mitotic index was below the control level until the 36 hr. The inhibitory effects on DNA synthesis and mitosis were more pronounced in the tar-UVA-treated epidermis than in the tar-treated epidermis. The S- and G2 + M fraction exceeded the control level in varying degrees during the whole experimental period. The results indicate that tar inhibits the epidermal DNA synthesis and mitosis by itself, and that the inhibitory effects of tar are intensified by the radiation of UVA.     

Are topical corticosteroids useful adjunctive therapy for the treatment of psoriasis with ultraviolet radiation? A review of the literature

Adjunctive topical corticosteroids are often administered with UV-B phototherapy or oral psoralen plus UV-A (PUVA) photochemotherapy for the treatment of psoriasis. Five studies comparing PUVA alone with PUVA and topical corticosteroid preparations showed more rapid rates of clearing and a smaller total UV-A exposure with the latter regimen. However, one study demonstrated a higher relapse rate in association with corticosteroid use. Further studies to better define these risks are recommended. Six of seven reports evaluating the use of topical corticosteroid preparations with UV-B phototherapy failed to demonstrate an advantage to this regimen when compared with UV-B phototherapy alone. Therefore, the use of a topical corticosteroid preparation with UV-B phototherapy for the treatment of psoriasis is not recommended.