Inhibitory effects of sodium valproate on oxidative phosphorylation

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 μM). At 240 μM, there was more than 50% inhibition of glutamate and α-ketoglutarate state 3 rates. Succinate state p rates were 80% of control values, and uncoupling was noted at 2400 μM 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.