[Protective effect of malotilate (diisopropyl 1,3-dithiol-2-ylidenemalonate) on chemical-induced hepatotoxicity].
Protective effect of malotilate on the liver injuries induced by several hepatotoxins was studied in mice and rats. Malotilate suppressed the elevation of plasma glutamate pyruvate transaminase (p-GPT) activity induced by chloroform (CHCl3) in rats when the animals were treated with 25 mg/kg or more dose of malotilate at 6 hours prior to the treatment with CHCl3. The effect was observed even in the rats treated with malotilate 24 or 48 hours prior to the treatment with CHCl3. Malotilate, when orally administered 6 hours prior to treatment with hepatotoxins such as CHCl3, allyl alcohol, bromobenzene, dimethylnitrosamine or thioacetamide, suppressed the elevation of p-GPT activity, liver triglyceride content and/or the decrease of bromosulphalein clearance induced by these hepatotoxins in mice. Anethole trithione, which was used as a possible protective agent against chemical-induced hepatotoxicity, tended to normalize changes in the parameters induced by the most of these hepatotoxins, but enhanced the elevation of p-GPT activity induced by CHCl3. In a case of CHCl3-induced liver injury, the protective effect of malotilate was histopathologically confirmed. Malotilate and anethole trithione reduced p-nitroanisole 0-demethylation activity in rat liver 6 hours after the administration but increased or tended to increase the activity 48 hours after the administration. Malotilate showed a protective effect on the liver injury induced by CHCl3 even when the activity of drug metabolizing enzymes in the liver was increased, although anethole trithione enhanced the CHCl3-induced liver injury regardless of the activity of drug metabolizing enzymes.
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D002725:Chloroform / Q000633:toxicity; D008099:Liver / Q000473:pathology; D008111:Liver Function Tests; D008314:Malonates / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D051381:Rats
D008314:Malonates; D002725:Chloroform; D000410:Alanine Transaminase; C024808:diisopropyl 1,3-dithiol-2-ylidenemalonate