Inhibition of cytochrome P-450 2E1 by diallyl sulfide and its metabolites.

摘要: Diallyl sulfide, a major flavor ingredient from garlic, was previously shown to inhibit chemically induced carcinogenesis and cytotoxicity in animal model systems. It modulated cytochrome P-450 compositions by inactivating 2E1 inducing 2B1. The present studies examined the inhibition of mediated p-nitrophenol hydroxylase activity diallyl sulfide its putative metabolites sulfoxide sulfone (DASO2). Each compound displayed competitive incubations using liver microsomes acetone-pretreated male Sprague-Dawley rats. Preincubation with DASO2 inactivated process that time- NADPH-dependent saturable, exhibited pseudo-first-order kinetics, protected alternate substrate, accompanied loss microsomal P-450-CO binding spectrum, unaffected exogenous nucleophile. Ki value for 188 microM maximal rate inactivation 0.32 min-1. ineffective ethoxyresorufin dealkylase, pentoxyresorufin or benzphetamine demethylase activity. Purified reconstituted system manner DASO2. metabolic conversion observed vivo vitro. results suggest inhibits metabolism substrates mechanisms via suicide-inhibitory action