Valproate-induced hepatic steatogenesis in rats.
The administration of high-dose valproic acid (VPA) (750 mg per kg) consistently produced significant microvesicular steatosis in mature Sprague-Dawley rats after 48 hr. Similar changes occurred in animals pretreated with phenobarbital which received a lower dose of VPA (350 mg per kg), but no steatosis was seen in animals treated with the low-dose VPA alone. The steatogenic effect of VPA is most likely mediated by a toxic metabolite. It can also be speculated that phenobarbital, by enhancing the inducing effects of the hepatic mixed-function oxidase system, may lead to increased conversion of VPA to a toxic metabolite. Young and weanling rats appeared to be resistant to the steatogenic effects of VPA. Reproduction of microvesicular steatosis in this experimental; model may permit exploration of factors that enhance or inhibit VPA-induced hepatic injury.
D000818:Animals; D001711:Biotransformation; D056486:Chemical and Drug Induced Liver Injury; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013231:Steatitis / Q000139:chemically induced*; D013997:Time Factors; D014635:Valproic Acid / Q000633:toxicity*
D014635:Valproic Acid; D010634:Phenobarbital