DIFFERENTIAL-EFFECTS OF DIETARY DIALLYL SULFIDE AND DIALLYL DISULFIDEON RAT INTESTINAL AND HEPATIC DRUG-METABOLIZING-ENZYMES

The chemopreventive properties of allyl sulfides on carcinogenesis may be related to the modulation of drug-metabolizing enzymes involved in carcinogen activation or detoxication. In order to investigate the ef fects of diallyl sulfide (DAS) and diallyl disulfide (DADS) on intesti nal and hepatic drug-metabolizing enzymes, rats were fed a diet contai ning 0.2% of either allyl sulfide. The DADS enhanced intestinal epoxid e hydrolase (EH) and cytochrome P-450 (P-450) 2B1/2 protein levels and the activities of pentoxy- and benzyl-oxyresorufin O-dealkylases, ary lhydrocarbon hydroxylase, microsomal epoxide hydrolase, p-nitrophenol UDP-glucuronyl transferase and glutathione S-transferase, and decrease d nitrosodimethylamine demethylase activity. In liver, DADS produced s imilar effects and, in addition, increased P-450 1A1/2 protein level a nd phenoxazone metabolizing activities (ethoxy- and methoxyresorufin O -dealkylases), p-hydroxybiphenyl UDP-glucuronyl transferase, and decre ased P-450 2E1 level. The DAS enhanced only EH activity in the small i ntestine and induced P-450 2B1/2 and epoxide hydrolase protein levels. In liver, DAS produced similar effects as DADS. The different effects of DAS on intestinal drug-metabolizing enzymes, compared to liver, co uld be ascribed to less metabolism of this compound in small intestine . It is also suggested that DAS and DADS may not yield the same metabo lites and therefore would have different effects on intestinal drug-me tabolizing enzymes.