Diazoxide preconditioning against seizure-induced oxidative injury is via the PI3K/Akt pathway in epileptic rat

Diazoxide (DZ), a highly selective opener of the mitochondrial ATP-sensitive potassium (mitoKATP) channel, has neuroprotective effects against neuronal cell death by reducing oxidative stress. However, the mechanism of DZ protecting hippocampal neurons against seizure-induced oxidative injury is unknown. In this study, we investigated DZ attenuating neuronal loss caused by pilocarpine-induced seizures in rat hippocampus. DZ attenuated oxidative stress injury by upregulating superoxide dismutase (SOD) activity and downregulating malondialdehyde (MDA) level, which could be abolished with 5-hydroxydecanoic acid, an inhibitor of mitoKATP. In addition, wortmannin, an inhibitor of phosphatidylinositol-3-kinase (PI3K), attenuated the changes in MDA and SOD levels after seizures. DZ could reduce oxidative injury induced by seizures by suppressing the activity of MDA and increasing the level of SOD in part by the PI3K/Akt pathway.

► Diazoxide (DZ) attenuates the neuronal loss in pilocarpine-induced seizures.
► DZ up-regulated of SOD activity and down-regulated of MDA quantity after seizures.
► The changes that DZ-induced can be abolished by preconditioning with Wortmannin (WTN).
► DZ protects neuron by suppressing oxidative stress via PI3K/Akt pathway.