Therapeutic effect of S-allylmercaptocysteine on acetaminophen-induced liver injury in mice.
S-allylmercaptocysteine is one of the water-soluble organosulfur compounds in ethanol extracts of garlic (Allium sativum L.). We had demonstrated earlier that treatment with S-allylmercaptocysteine before acetaminophen administration protects mice against acetaminophen-induced hepatotoxicity. In this study, we examined the therapeutic effect of S-allylmercaptocysteine treatment after acetaminophen administration. A single dose of S-allylmercaptocysteine (200 mg/kg, p.o.) to mice 0.5 h after acetaminophen administration (500 mg/kg, p.o.) significantly suppressed both the increase in plasma alanine aminotransferase activity and the hepatic necrosis, and also reduced acetaminophen-induced mortality from 43% to 0%. These data indicate that S-allylmercaptocysteine is useful as an antidote for acetaminophen overdose. S-allylmercaptocysteine significantly suppressed hepatic cytochrome P450 2E1 (CYP2E1) activity and induction of inducible 70-kDa heat shock protein, a marker of acetaminophen arylation of protein. These results suggest that S-allylmercaptocysteine exerts its protective effect by inhibition of CYP2E1 activity, which leads to the suppression of acetaminophen arylation of hepatic protein.
Sumioka
I
I
Healthcare Research Institute, Wakunaga Pharmaceutical Co., Ltd., 1624 Shimokotachi, Koda-cho, Takata-gun, Hiroshima 739-1195, Japan.
Matsura
T
T
Yamada
K
K
D000082:Acetaminophen / Q000378:metabolism / Q000633:toxicity*; D018712:Analgesics, Non-Narcotic / Q000633:toxicity*; D000818:Animals; D003545:Cysteine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D005978:Glutathione / Q000032:analysis; D019803:Glutathione Disulfide / Q000032:analysis; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D020011:Protective Agents / Q000627:therapeutic use*
D018712:Analgesics, Non-Narcotic; D018840:HSP70 Heat-Shock Proteins; D020011:Protective Agents; C086300:S-allylmercaptocysteine; D000082:Acetaminophen; D019392:Cytochrome P-450 CYP2E1; D005978:Glutathione; D003545:Cysteine; D019803:Glutathione Disulfide