A labile sulfur in trisulfide affects cytochrome P-450 dependent lipid peroxidation in rat liver microsomes

The effects of trisulfide derivatives were studied on cytochrome P-450-depe ndent lipid peroxidation using rat liver microsomal systems. Cytochrome P-4 50-dependent lipid peroxidation was induced by carbon tetrachloride or tert -butylhydroperoxide and was evident by an increase in thiobarbituric acid-r eactive substances (TBA-RS) and oxygen consumption. In these cytochrome P-4 50-dependent lipid peroxidation systems, pretreatment of microsome with tri sulfide derivatives (cystine trisulfide and thiocyclam) significantly inhib ited TBA-RS formation and oxygen consumption compared with disulfide or thi ol analogs (cystine, nereistoxin, or cysteine). The labile sulfur contained in trisulfide disappeared during incubation with liver microsomes. In the CCl4-induced lipid peroxidation system, the cytochrome P-450 level and NAD( P)H-cytochrome P-450 reductase activity were significantly decreased by the addition of trisulfide derivatives. Therefore, in cytochrome P-450-depende nt lipid peroxidation system, the potential effects of trisulfide appear to be mediated via enzyme inhibition. These results suggest that pretreatment of the trisulfide derivatives may affect the toxic function of exogenous x enobiotics or drugs, which are reduced by the liver enzyme cytochrome P-450 to radical species. (C) 1998 Elsevier Science Ireland Ltd. All rights rese rved.