MECHANISMS OF PROTECTION BY S-ALLYLMERCAPTOCYSTEINE AGAINST ACETAMINOPHEN-INDUCED LIVER-INJURY IN MICE

S-Allylmercaptocysteine (SAMC), one of the water-soluble organosulfur compounds in ethanol extracts of garlic (Allium sativum L.), has been shown to protect mice against acetaminophen (APAP)-induced liver injur y. In this study, we examined the mechanisms underlying this hepatopro tection. SAMC (100 mg/kg, p.o.) given 2 and 24 hr before APAP administ ration (500 mg/kg, p.o.) suppressed the plasma alanine aminotransferas e activity increases 3 to 12 hr after APAP administration significantl y. The hepatic reduced glutathione levels of vehicle-pretreated mice d ecreased 1 to 6 hr after APAP administration, but SAMC pretreatment su ppressed the reductions 1 to 6 hr after APAP administration significan tly. These inhibitory effects of SAMC were dose-dependent (50-200 mg/k g) 6 hr after APAP administration. As SAMC pretreatment (50 - 200 mg/k g) suppressed hepatic cytochrome P450 2E1-dependent N-nitrosodimethyla mine demethylase activity significantly in a dose-dependent manner, we suggest that one of its protective mechanisms is inhibition of cytoch rome P450 2E1 activity. SAMC pretreatment also suppressed the increase in hepatic lipid peroxidation and the decrease in hepatic reduced coe nzyme Q(9) (CoQ(9)H(2)) levels 6 hr after APAP administration. The hep atic CoQ(9)H(2) content of the SAMC pretreatment group was maintained at the normal level. Therefore, we suggest that another hepatoprotecti ve mechanism of SAMC may be attributable to its antioxidant activity.