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Protection Against Sodium Valproate Injury in Isolated Hepatocytes by α‐Tocopherol and N,N'‐Diphenyl‐ p ‐phenylenediamine
Author(s) -
BUCHI KENNETH N.,
GRAY PHILLIP D.,
ROLLINS DOUGLAS E.,
TOLMAN KEITH G.
Publication year - 1984
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1984.tb01823.x
Subject(s) - toxicity , chemistry , lipid peroxidation , valproic acid , pharmacology , lactate dehydrogenase , vitamin e , tocopherol , hepatocyte , antioxidant , acute toxicity , biochemistry , enzyme , medicine , in vitro , organic chemistry , psychiatry , epilepsy
The possibility that lipid peroxidation is involved in valproic acid (VPA) hepatotoxicity was explored by testing the ability of the free‐radical scavengers α‐tocopherol (vitamin E) and N,N'‐diphenyl‐ p ‐phenylenediamine (DPPD) to protect against VPA toxicity. Rat hepatocyte cultures were treated with toxic doses of VPA, in conjunction with varying doses of vitamin E and DPPD. Lactate dehydrogenase (LDH) release into the culture media was used to calculate an LDH index as a measure of toxicity. Vitamin E afforded increasing protection against VPA toxicity at concentrations of 1.0 to 4.0 μM but then leveled off and did not give complete protection at concentrations up to 8.0 μM. No protection was seen at less than 1.0 μM. DPPD showed increasing protection from 0.05 to 0.50 μM, with complete protection at the highest concentration. These data indicate that VPA toxicity can be prevented by simultaneous administration of free‐radical scavengers and support the concept that VPA hepatotoxicity is due to lipid peroxidation.