Human hepatocytes are protected from ethanol-induced cytotoxicity by DADS via CYP2E1 inhibition.

ABSTRACT

We investigated the protective effects of diallyl disulfide (DADS), a potent inhibitor of cytochrome P450 2E1 (CYP2E1), on ethanol-induced toxicity in human hepatocytes. We found a clear dose-dependent response between ethanol and CYP2E1 activity. The ethanol-dependent CYP2E1 enzyme activity and protein expression, lactate dehydrogenase and aspartate transaminase release, malondialdehyde formation and caspase-3 activity decreased dramatically in the presence of DADS. Furthermore, DADS increased the hepatocellular glutathione (GSH) content and prevented the ethanol-dependent cellular GSH depletion. Our data show that DADS reduces ethanol-induced toxicity in human hepatocytes by reducing CYP2E1 activity and/or stabilizing the cellular GSH content, which might be of therapeutic interest.