The protective effect of N-acetylcysteine on UVB-induced immunosuppression by inhibition of the action of cis-urocanic acid.
A recent study has shown that N-acetylcysteine (NAC) not only has sun-protective properties but also inhibits the UVB-induced suppression of contact hypersensitivity (CHS) in mice. Because NAC does not absorb any UVA (320-400 nm radiation) or UVB (290-320 nm radiation) we have studied the underlying mechanism of protection. Irradiation of solutions of plasmid DNA with UVC (200-290 nm radiation) (10 J m-2) resulted in the formation of cyclobutane pyrimidine dimers, but the extent to which this occurred was not affected by the presence of NAC as was determined by an in vitro T4 endonuclease assay. N-acetylcysteine proved not to have any effect on the photoisomerization of trans-urocanic acid (UCA) to its cis-form in vitro; at equilibrium, approximately 55% cis-UCA was formed. The same percentage was also found in vivo on exposure of mice to UVB (15 kJ m-2). Topical application of NAC 30 min prior to irradiation did not have any influence as well on the photoisomerization of trans- to cis-UCA. These in vivo experiments were performed under the same conditions used previously to show the protective effect of NAC against UVB-induced suppression of CHS. We conclude that this protection of NAC is at least partly based on interference in the role of cis-UCA in UVB-induced suppression of CHS. This conclusion is supported by the observation that NAC completely inhibits the suppression of CHS by cis-UCA administered to mice that were always kept in the dark. In the same range of doses as used in the present study, it was shown in our previous study that NAC alone does not affect the CHS response.
Hemelaar
P J
PJ
Department of Medicinal Photochemistry, Leiden University, Netherlands.
Beijersbergen van Henegouwen
G M
GM
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D003877:Dermatitis, Contact / Q000276:immunology; D007108:Immune Tolerance / Q000187:drug effects* / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013473:Sunscreening Agents / Q000494:pharmacology*; D014466:Ultraviolet Rays / Q000009:adverse effects*; D014560:Urocanic Acid / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D013473:Sunscreening Agents; D014560:Urocanic Acid; D000111:Acetylcysteine