The naturally occurring organosulfur compounds (OSCs) diallyl sulfide (DAS), diallyl disulfide (DADS), dipropyl sulfide (DPS), and dipropyl disulfide (DPDS) were studied with respect to their effects on hepatic, intestinal, renal, and pulmonary phase II drug metabolizing enzymes, i.e., glutathione S-transferase (GST), microsomal epoxide hydrolase (mEH), quinone reductase (QR), and UDP-glucuronosyltransferase (UGT). OSCs were administered po to male SPF Wistar rats. In addition to assays of total enzyme activity, the ability of OSCs to modify the levels of mEH and rGSTA1/A2, A3/A5, M1, M2, and P1 was assessed by Western blotting. Remarkably, DADS significantly increased all Phase II enzyme activities, except the pulmonary mEH. It was noteworthy that only DADS induced QR activity. DAS, DPS, and DPDS induced mEH, GST, and UGT activities in the liver. Interestingly, DAS, DPS, and DPDS significantly decreased renal GST activity. In the same manner, DAS, DPS, and DPDS decreased rGSTA1/A2 and A3/A5 levels in the kidney. Conversely, all OSCs were able to induce GST of alpha and mu classes in the liver. In the intestine, DADS and DAS increased rGSTA1/A2, M2, and P1, while rGSTA3/A5 and M2 were only increased by DADS. In addition, DADS induced rGSTP1 dramatically in the four tissues analyzed. DADS also increased the mEH levels in the liver, intestine, and kidney, while DAS and DPS moderately induced mEH level in the liver. This study brings additional insights into the effects of OSCs on Phase II enzymes and suggests that DADS could be a promising chemopreventive agent considering its pleiotropic capacity of induction.
Copyright 1999 Academic Press.