Early changes in hepatic redox homeostasis following treatment with a single dose of valproic acid.
Changes in reduced glutathione (GSH) and pyridine nucleotide phosphate levels as well as in the activities of the glutathione peroxidase-reductase system and glucose-6-phosphate dehydrogenase have been studied in rats after a single i.p. administration of various doses of valproic acid (VPA). GSH level decreased in a dose-dependent relation. At the end of 180 min GSH levels either returned to control limits (lower doses) or showed a tendency to normalize (higher doses). GSH loss was paralleled by the reduction in glutathione reductase activity. A significant NADPH reduction was also seen after animal exposure to high VPA doses. At the end of 180 min a maximal NADPH decrease was reached. The activities of both glutathione peroxidase and glucose-6-phosphate dehydrogenase were suppressed irrespective of whether animals were given low or high VPA doses.
Cotariu
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Department of Biochemical Pathology, Assaf Harofeh Medical Center, Sackler School of Medicine, Zerifin, Israel.
Evans
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Zaidman
J L
JL
Marcus
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O
D000818:Animals; D005260:Female; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D009249:NADP / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D014635:Valproic Acid / Q000494:pharmacology*
D009249:NADP; D014635:Valproic Acid; D005954:Glucosephosphate Dehydrogenase; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005978:Glutathione