Topically applied eicosapentaenoic acid protects against local immunosuppression induced by UVB irradiation, cis-urocanic acid and thymidine dinucleotides

UVB-induced immunosuppression, a promoter of photocarcinogenesis, involves the formation of pyrimidine dimers and cis-urocanic acid (cis-UCA), but rea ctive oxygen species (ROS) also plays an important role. Eicosapentaenoic a cid (EPA) can inhibit photocarcinogenesis, but due to its polyunsaturated n ature it is susceptible to oxidative damage by ROS, The antioxidant defense system may therefore be challenged upon ultraviolet-B (UVB) irradiation in the presence of EPA, We investigated whether topically applied EPA in mice could protect against local immunosuppression (contact hypersensitivity re sponse to dinitrofluorobenzene) induced by UVB radiation (1.5 J/cm(2)), or topically applied cis-UCA (150 nmol/cm(2)) or thymidine dinucleotides (pTpT ) (5 nmol/cm(2)), The influence of EPA on epidermal lipid peroxidation and antioxidant status was also measured, UVB irradiation, cis-UCA and pTpT all caused 70% immunosuppression, Topical pretreatment of mice with EPA partia lly protected against immunosuppression; the EPA dose needed to accomplish this was 10 nmol/cm(2) for WE irradiation, 100 nmol/cm(2) for cis-UCA and 1 000 nmol/cm(2) for pTpT, Higher EPA doses caused higher UVB-induced lipid p eroxidation and lower vitamin C levels. Glutathione only decreased with the highest EPA dose whereas vitamin E was not decreased after UVB irradiation . In conclusion, topically applied EPA protects against UVB-, cis-UCA- and pTpT-induced immunosuppression and maintenance of an adequate antioxidant d efense seems to be an important prerequisite for the protective action by E PA.