Histological, ultrastructural and mitochondrial oxidative phosphorylation studies in liver of rats chronically treated with oral valproic acid.
The effects of oral administration of valproic acid (VPA) have been studied on the liver of female adult Wistar rats, at doses of 60 and 120 mg/kg/day during 4 and 18 weeks (periods I and II). Other groups received the same doses of VPA with phenobarbital (PB). The animals developed periportal steatosis, more intense at the end of period II and in groups non-induced by PB, and also some degree of mitochondrial swelling. An uncoupling of the oxidative phosphorylation was also evident with both doses in the non-induced groups, and only with the high dose of VPA in the induced group. An in vitro study on isolated liver mitochondria showed uncoupling only with very high concentration of VPA (10 mM). We comment on these findings and propose a chronic model of experimental hepatotoxicity of oral VPA in the rat.
D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000648:ultrastructure; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D051381:Rats; D014635:Valproic Acid / Q000494:pharmacology*
D014635:Valproic Acid; D000410:Alanine Transaminase