Isao Sumioka (1), Tatsuya Matsura (2), Shigeo Kasuga (1), Yoichi Itakura
(1) and Kazuo Yamada (2,*)
(1) Institute for OTC Research, Wakunaga Pharmaceutical Co., Ltd., 1624
Shimokotachi, Koda-cho, Takata-gun, Hiroshima 739-1105, Japan
(2) Department of Biochemistry, Faculty of Medicine, Tottori University,
86 Nishi-cho, Yonago 683-8503, Japan
(*) To whom correspondence should be addressed.
Abstract: 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
injury. In this study, we examined the mechanisms underlying this hepatoprotection.
SAMC (100 mg/kg, p.o.) given 2 and 24 hr before APAP administration (500
mg/kg, p.o.) suppressed the plasma alanine aminotransferase activity increases
3 to 12 hr after APAP administration significantly. The hepatic reduced
glutathione levels of vehicle-pretreated mice decreased 1 to 6 hr after
APAP administration, but SAMC pretreatment suppressed the reductions 1 to
6 hr after APAP administration significantly. These inhibitory effects of
SAMC were dose-dependent (50 - 200 mg/kg) 6 hr after APAP administration.
As SAMC pretreatment (50 - 200 mg/kg) suppressed hepatic cytochrome P450
2E1-dependent N-nitroso-dimethylamine demethylase activity significantly
in a dose-dependent manner, we suggest that one of its protective mechanisms
is inhibition of cytochrome P450 2E1 activity. SAMC pretreatment also suppressed
the increase in hepatic lipid peroxidation and the decrease in hepatic reduced
coenzyme Q9 (CoQ9H2) levels 6 hr after
APAP administration. The hepatic CoQ9H2 content of
the SAMC pretreatment group was maintained at the normal level. Therefore,
we suggest that another hepatoprotective mechanism of SAMC may be attributable
to its antioxidant activity.
Keywords: Acetaminophen, Hepatoprotective agent, S-Allylmercaptocysteine,
Garlic, Cytochrome P450 2E1