Antioxidant and pro-oxidant effect of the thiolic compounds N-acetyl-L-cysteine and glutathione against free radical-induced lipid peroxidation.

The antioxidant ability of thiol compounds has been the subject of much of the current research about oxidative stress. The direct scavenging of hydroxyl radicals by thiols has been suggested as their protection mechanisms. Nevertheless, the interaction of thiols with reactive radicals can generate thiyl radicals, which, in turn, may impart a pro-oxidant function. The purpose of this study has been to establish the effect of the thiol compounds N-acetyl-L-cysteine (NAC) and glutathione (GSH) against the peroxidative processes involving membrane lipids. The results obtained support the ability of NAC and GSH to suppress the 2,2'-azobis-(2-amidinopropane) dihydrochloride (AAPH)-dependent or to enhance the Fe2+/H2O2-dependent oxidative actions. The evaluation of thiobarbituric acid reactive substances (TBARS) production, the study of the influence of oxidants on membrane fluidity and the measurements of the changes in the fluorescence of bilayer probes, such as 3-(p-(6-phenyl)-1,3,5-hexatrienyl)phenylpropionic acid (DPH-PA), have shown the antioxidant and pro-oxidant effects of both NAC and GSH. Also their dependence on the nature of the radicals generated by the oxidative systems used has been shown. The use of ESR spectroscopy has allowed us to establish the ability of these compounds to scavenge the AAPH-derived radicals, to determine the formation of thiyl radicals in the iron-mediated oxidation and to evaluate the enhanced production of hydroxyl radicals by NAC and GSH.