Toxicol Lett. 1998 Nov 12;99(3):191-8.  

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

Ogasawara Y, Isoda S, Tanabe S.

Department of Hygienic Chemistry, Meiji College of Pharmacy, Tokyo, Japan.

The effects of trisulfide derivatives were studied on cytochrome P-450-dependent
lipid peroxidation using rat liver microsomal systems. Cytochrome
P-450-dependent lipid peroxidation was induced by carbon tetrachloride or
tert-butylhydroperoxide and was evident by an increase in thiobarbituric
acid-reactive substances (TBA-RS) and oxygen consumption. In these cytochrome
P-450-dependent lipid peroxidation systems, pretreatment of microsome with
trisulfide derivatives (cystine trisulfide and thiocyclam) significantly
inhibited TBA-RS formation and oxygen consumption compared with disulfide or
thiol 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-dependent
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 xenobiotics or
drugs, which are reduced by the liver enzyme cytochrome P-450 to radical
species.

PMID: 9862285 [PubMed - indexed for MEDLINE]