title: Diallyl trisulfide protects rats from carbon tetrachloride-induced liver injury.
abstract: 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 (CCl(4))-induced acute liver injury in rats. Rats were pretreated with diallyl trisulfide (DATS) i.g. at a dose of 500 micromol/kg body weight for 5 d. On d 6, CCl(4) was administered i.g. at a dose of 2.5 mL/kg body weight. Twenty-four hours after CCl(4) administration, rats were killed and plasma and liver samples collected. DATS pretreatment significantly suppressed the CCl(4)-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 CCl(4)-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 micromol/kg body weight) to rats for 5 d. Only the allyl group-containing DATS and allyl methyl trisulfide enhanced these activities.
authors.affiliation: Department of Applied Life Sciences, Nihon University Graduate School of Bioresource Sciences, Kanagawa, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Hosono-Fukao
authors.forename: Takashi
authors.initials: T
authors.lastname: Hosono
authors.forename: Taiichiro
authors.initials: T
authors.lastname: Seki
authors.forename: Toyohiko
authors.initials: T
authors.lastname: Ariga
mesh_terms: D000410:Alanine Transaminase / Q000187:drug effects / Q000378:metabolism; D000498:Allyl Compounds / Q000494:pharmacology*; D000818:Animals; D001219:Aspartate Aminotransferases / Q000187:drug effects / Q000378:metabolism; D002252:Carbon Tetrachloride Poisoning / Q000473:pathology / Q000517:prevention & control*; D019362:Cytochrome P-450 CYP2B1 / Q000187:drug effects / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013024:Soybean Oil / Q000494:pharmacology; D013440:Sulfides / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D015430:Weight Gain
chemical_list: D000498:Allyl Compounds; D013440:Sulfides; D017392:Thiobarbituric Acid Reactive Substances; C042577:diallyl trisulfide; D013024:Soybean Oil; D019392:Cytochrome P-450 CYP2E1; D019362:Cytochrome P-450 CYP2B1; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase