Inhibition of the hepatotoxicity of paracetamol and its irreversible binding to rat liver microsomal protein.
Dithiocarb and (+)-cyanidanol-3-prevented paracetamol-induced liver injury in rats in vivo. Both, as well as two other antihepatotoxic agents, deanol and DMSO, inhibited covalent binding of [3H]-paracetamol to rat liver microsomal proteins in vitro. Dithiocarb and (+)-cyanidanol-3 were the most effective inhibitors. The concentrations of the antidotes yielding 50% inhibition (I50) valued 1 . 8 x 10(-5) M for dithiocarb and 2 . 1 x 10(-5) M for (+)-cyanidanol-3.
D000082:Acetaminophen / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D002392:Catechin / Q000494:pharmacology; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D003642:Deanol / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004050:Ditiocarb / Q000494:pharmacology; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D013997:Time Factors
D003642:Deanol; D000082:Acetaminophen; D002392:Catechin; D004050:Ditiocarb; D004121:Dimethyl Sulfoxide; D010634:Phenobarbital