Biochemical mode of action of a hepatoprotective drug: observations on (+)-catechin.
(+)-Catechin inhibits the hepatic lipid accumulation resulting from chronic ethanol ingestion in the rat. Experiments have been carried out to determine the mechanisms underlying this effect. Ethanol was administered (2.0 g/kg intraperitoneally) to Wistar rats and 90 min later 1 microCi [U-14C] palmitic acid injected intraperitoneally. Animals were sacrificed 10 min after injection of palmitate and the liver freeze-clamped. Ethanol caused a 250% increase in the hepatic lactate:pyruvate (L:P) ratio and a 100% increase in the amount of [U-14C] palmitate incorporated into the hepatic lipids when compared with controls. Pretreatment of animals with (+)-catechin (200 mg/kg orally) at 24 and 0 hr before ethanol caused significant reductions in the L:P ratio and amount of radioactivity incorporated into hepatic lipids, when compared with animals receiving ethanol alone. (+)-Catechin also stimulated 14CO2 production from [1-14C] palmitate by liver slices taken from rats 90 min after ethanol administration. Thus, (+)-catechin appears to mediate its effect on fat accumulation partly by correcting the ethanol-induced alterations in hepatic redox state as there is no evidence of the drug inhibiting ethanol metabolism.
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D002392:Catechin / Q000494:pharmacology*; D000431:Ethanol / Q000633:toxicity*; D005235:Fatty Liver, Alcoholic / Q000201:enzymology; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats; D011919:Rats, Inbred Strains; D014280:Triglycerides / Q000378:metabolism
D001578:Benzopyrans; D007773:Lactates; D011773:Pyruvates; D014280:Triglycerides; D019344:Lactic Acid; D000431:Ethanol; D019289:Pyruvic Acid; D002392:Catechin; D005969:Glutamate Dehydrogenase