Green tea protects against psoralen plus ultraviolet A-induced photochemical damage to skin

The use of psoralens combined with exposure to ultraviolet A radiation is a major form of treatment for psoriasis and a number of other common skin di seases. Although psoralen plus ultraviolet A treatment is highly effective, careful follow-up cohort studies have shown that it greatly increases risk for the development of cutaneous squamous cell carcinoma and melanoma, Str ategies to reduce the risk of cancer development in psoralen plus ultraviol et A-treated populations are highly desirable. In prior studies, we demonst rated that green tea and constituent polyphenols protect against ultraviole t B-induced carcinogenesis and reduce the growth rate of established tumors in skin. In this study, we show that pre- and post-treatment with standard ized green tea extract in psoralen plus ultraviolet A treatment populations abrogates the psoralen plus ultraviolet A-induced photochemical damage to skin. Intact mouse and human skin and reconstituted human skin were employe d to assess the effect of both topical and oral administration of standardi zed green tea extract against psoralen plus ultraviolet A-induced photodama ge. Oral administration of standardized green tea extract prior to and duri ng multiple psoralen plus ultraviolet A treatments reduced hyperplasia and hyperkeratosis in murine skin. Standardized green tea extract treatment als o inhibited accumulation of c-fos and p53 protein induction following a sin gle exposure to psoralen plus ultraviolet A. c-fos and p53 positive cells i n psoralen plus ultraviolet A-treated skin were found to be increased by 55 .4 +/- 13.6% and 62.3 +/- 10.5%, respectively, compared with saline-treated unexposed control skin. Oral administration of 0.4 or 0.8% standardized gr een tea extract inhibited c-fos protein accumulation by 18.5% and 46.2% (p < 0.05), respectively, and p53 protein accumulation by 26.1% and 54.3% (p<0 .05), respectively. Similarly proliferating cell nuclear antigen staining, a marker of cell proliferation was induced (73.7%) in psoralen plus ultravi olet A-treated skin. Oral administration of 0.4% or 0.8% standardized green tea extract 1 d after psoralen plus ultraviolet A treatment was effective in reducing psoralen plus ultraviolet A-induced inflammatory responses incl uding erythema and edema formation. When standardized green tea extract was applied to EpiDerm, a reconstituted human skin equivalent, psoralen plus u ltraviolet A-induced 8-methoxypsoralen-DNA adduct formation and p53 protein accumulation were inhibited. Topical application of 0.2mg 8-methoxypsorale n per cm(2) followed by exposure to ultraviolet A (2.5J per cm(2)) resulted in delayed erythema formation in human subjects. Pretreatment of human ski n with topical application of 0.2mg standardized green tea extract per cm2 30 min prior to psoralen plus ultraviolet A treatment resulted in an almost complete abrogation of psoralen plus ultraviolet A-induced erythema, In su mmary, these data demonstrate that standardized green tea extract protects against psoralen plus ultraviolet A-induced phototoxicity by inhibiting DNA damage and diminishing the inflammatory effects of this modality.