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Biochemical, Molecular, and Genetic Mechanisms

Diallyl Trisulfide Protects Rats from Carbon Tetrachloride-Induced Liver Injury^1,2,3

Department of Applied Life Sciences, Nihon University Graduate School of Bioresource Sciences, Kanagawa 252-8510, Japan

Alk(en)yl sulfides have been found to be responsible for the anticancer, antithrombotic, and antioxidant effects of garlic. We sought to identify the most potent structure of sulfides that exhibits a hepatoprotective effect against carbon tetrachloride (CCl₄)-induced acute liver injury in rats. Rats were pretreated with diallyl trisulfide (DATS) i.g. at a dose of 500 µmol/kg body weight for 5 d. On d 6, CCl₄ was administered i.g. at a dose of 2.5 mL/kg body weight. Twenty-four hours after CCl₄ administration, rats were killed and plasma and liver samples collected. DATS pretreatment significantly suppressed the CCl₄-induced elevation of plasma aspartate aminotransferase and alanine aminotransferase activities (P < 0.05). Histological observations supported the hepatoprotective effects. Western blot and spectrophotometric analyses indicated that DATS suppressed cytochrome P450 2E1 activity and its protein level and elevated those of glutathione S-transferase. Dipropyl trisulfide (DPTS), which is a saturated alkyl chain analogue of DATS, did not affect CCl₄-induced liver toxicity or drug-metabolizing enzymes. These results suggest that hepatoprotective activity of trisulfides is due to their regulation of drug-metabolizing enzymes. Furthermore, the effects of 6 kinds of alk(en)yl trisulfides, including DATS and DPTS, on phase II enzyme activity were examined in rats. Alk(en)yl trisulfides were administered i.g. (500 µmol/kg body weight) to rats for 5 d. Only the allyl group-containing DATS and allyl methyl trisulfide enhanced these activities.

^* To whom correspondence should be addressed. E-mail: tseki{at}brs.nihon-u.ac.jp.

Manuscript received 4 May 2009. Initial review completed 3 June 2009. Revision accepted 11 September 2009.