Influence of dithiocarb, (+)-catechin and silybine on halothane hepatotoxicity in the hypoxic rat model.
In phenobarbital (phenemalum NFN)-pretreated male rats exposed to 1% halothane for 2 hrs under hypoxic conditions (10% O2), significant increases in serum enzyme activities of alanine aminotransferase and sorbitol dehydrogenase were observed 24 and 48 hrs later indicating liver damage. In this known model of halothane hepatotoxicity, pretreatment with (+)-catechin (200 mg/kg orally) or silybine (150 mg/kg orally) protected against halothane-induced liver injury, whereas diethyldithiocarbamate (200 mg/kg orally) failed to be effective. Halothane decreased the concentration of reduced glutathione in liver only under hypoxic conditions indicating that glutathione might be involved in the non-oxidative metabolic pathways of halothane. Free fluoride in plasma was used as a measure of non-oxidative defluorination of halothane. Higher plasma fluoride levels were observed under conditions which led to hepatotoxicity but did not correlate with the protective effects of the antidotes. This further supports the assumption that 2-chloro-1,1,1-trifluoroethane might be the radical intermediate responsible for halothane hepatotoxicity.
D000818:Animals; D001578:Benzopyrans / Q000627:therapeutic use*; D002392:Catechin / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D004050:Ditiocarb / Q000627:therapeutic use*; D005419:Flavonoids / Q000627:therapeutic use*; D005459:Fluorides / Q000097:blood; D005978:Glutathione / Q000378:metabolism; D006221:Halothane / Q000633:toxicity*; D008099:Liver / Q000378:metabolism; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012838:Silymarin / Q000627:therapeutic use*; D013859:Thiocarbamates / Q000627:therapeutic use*
D001578:Benzopyrans; D005419:Flavonoids; D012838:Silymarin; D013859:Thiocarbamates; D002392:Catechin; D004050:Ditiocarb; D005978:Glutathione; D005459:Fluorides; D006221:Halothane; D010634:Phenobarbital