Glutathione ethylester protects against local and systemic suppression of contact hypersensitivity induced by ultraviolet B radiation in mice.
Irradiation of the skin with ultraviolet B (UVB) radiation causes a local and systemic suppression of T-cell-mediated immune responses. Recently, N-acetylcysteine was found to protect against UVB-radiation-induced immunosuppression and several other types of damage induced by UV radiation. The protective effects appeared to be caused by an increase in glutathione (GSH). This increase was limited by feedback inhibition by GSH of its own synthesis. Better results were expected with the use of GSH derivatives which do not require de novo synthesis, such as GSH esters. In this study, topical application of glutathione ethylester (GSH-Et) was found to increase the epidermal GSH level in mice in a manner that was dependent on dose to 1234% of the control value at the highest dose tested (2.0 micromol/cm2). This resulted in dose-dependent protection against UVB-radiation-induced suppression of contact hypersensitivity. The highest dose of GSH-Et tested provided 83% protection against local suppression and 62% protection against systemic suppression. Immunosuppression induced by topically applied cis-urocanic acid (cis-UCA) was prevented completely. Although an effect on the formation of pyrimidine dimers cannot be excluded, the protective effect of GSH-Et seems to be mediated through inhibition of the action of cis-UCA.
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Department of Medicinal Photochemistry, Leiden/Amsterdam Center for Drug Research, University of Leiden, The Netherlands.
Beijersbergen van Henegouwen
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D000818:Animals; D003877:Dermatitis, Contact / Q000209:etiology / Q000517:prevention & control*; D004139:Dinitrofluorobenzene; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000031:analogs & derivatives* / Q000187:drug effects* / Q000378:metabolism / Q000494:pharmacology; D007111:Immunity, Cellular / Q000187:drug effects / Q000528:radiation effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000187:drug effects* / Q000528:radiation effects; D014466:Ultraviolet Rays; D014560:Urocanic Acid / Q000494:pharmacology
C042431:S-ethyl glutathione; D004139:Dinitrofluorobenzene; D014560:Urocanic Acid; D005978:Glutathione