Cytotoxicity of unsaturated metabolites of valproic acid and protection by vitamins C and E in glutathione-depleted rat hepatocytes

Valproic acid (VPA) and the unsaturated metabolites, 2-ene VPA and (E)-2,(Z)-3′-diene VPA, demonstrated dose-dependent cytotoxicity in primary cultures of rat hepatocytes, as evaluated by lactate dehydrogenase (LDH) leakage. Cellular glutathione (GSH) was depleted by adding buthionine sulfoximine (B...

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Veröffentlicht in:	Toxicology (Amsterdam) 1996-08, Vol.112 (1), p.69-85
Hauptverfasser:	Jurima-romet, Malle, Abbott, Frank S., Tang, Wei, Huang, Hide S., Whitehouse, larry W.
Format:	Artikel
Sprache:	eng
Schlagworte:	Analysis of Variance Animals Anticonvulsants - metabolism Anticonvulsants - toxicity Ascorbic Acid - pharmacology Biological and medical sciences Cells, Cultured Chromatography, Liquid Cytochrome P-450 Enzyme System - biosynthesis Cytotoxicity Dose-Response Relationship, Drug Drug Synergism Drug toxicity and drugs side effects treatment Enzyme Induction - drug effects Enzyme Inhibitors - metabolism Enzyme Inhibitors - toxicity Glutathione Glutathione - metabolism Homeostasis L-Lactate Dehydrogenase - metabolism Liver - cytology Liver - drug effects Liver - enzymology Male Mass Spectrometry Medical sciences Metabolism Methionine - analogs & derivatives Methionine - toxicity Pharmacology. Drug treatments Phenobarbital - toxicity Pregnenolone Carbonitrile - toxicity Rat hepatocytes Rats Rats, Inbred F344 Toxicity: digestive system Valproic acid Valproic Acid - metabolism Valproic Acid - toxicity Vitamin C Vitamin E Vitamin E - pharmacology
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