Inhibitory effects of sodium valproate on oxidative phosphorylation

作者：Richard Haas, B. Chir, David A. Stumpf, Janice K. Parks, Luis A. Eguren · 发表于：Neurology · 年份：1981 · DOI：10.1212/wnl.31.11.1473 · 被引用次数：95 · 研究领域：Pharmacological Effects and Toxicity Studies、Boron Compounds in Chemistry、Metabolism and Genetic Disorders

Sodium valproate (VP) inhibited oxidative phosphorylation in isolated rat liver mitochondria. State 3 rates of oxygen consumption with glutamate as substrate were 80% of control values at a low VP concentration (24 microM). At 240 microM, there was more than 50% inhibition of glutamate and alpha-ketoglutarate state 3 rates. Succinate state 3 rates were 80% of control values, and uncoupling was noted at 2400 microM VP. These VP effects were similar to those of propionate and isovalerate, suggesting a common mechanism of toxicity. Inhibition of mitochondrial oxidative phosphorylation may explain why VP intoxication causes a hepatocerebral disorder that resembles Reye syndrome.