Evaluation of the cytotoxicity of sodium valproate on primary cultured rat hepatocytes.
Primary cultured rat hepatocytes were used to study the cytotoxicity of sodium valproate (VPA). Cytotoxicity was monitored by measurement of leakage of intracellular enzymes into the culture medium: lactate dehydrogenase (LDH), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT). The effects of D,L-carnitine and albumin administration on the cytotoxicity were evaluated. LDH leakage rose with an increasing dose of VPA. Administrations of D,L-carnitine and albumin reduced VPA hepatotoxicity. Our data suggest that VPA-induced hepatotoxicity is dose-related and may be modulated by serum carnitine and albumin levels.
Takeuchi
T
T
Department of Pediatrics, Kansai Medical University, Osaka, Japan.
Sugimoto
T
T
Nishida
N
N
Kobayashi
Y
Y
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002331:Carnitine / Q000494:pharmacology; D002478:Cells, Cultured; D006801:Humans; D007700:Kinetics; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D014635:Valproic Acid / Q000633:toxicity*
D012710:Serum Albumin, Bovine; D014635:Valproic Acid; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D002331:Carnitine