title: Diazoxide preconditioning against seizure-induced oxidative injury is via the PI3K/Akt pathway in epileptic rat.
abstract: Diazoxide (DZ), a highly selective opener of the mitochondrial ATP-sensitive potassium (mitoK(ATP)) 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 mitoK(ATP). 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.
authors: Department of Neurology, Qilu Hospital, Shandong University, 44#, Wenhua Xi Road, Jinan 250012, China.
authors: Yuan
authors: Y
authors: Xue
authors: Nanchang
authors: N
authors: Xie
authors: Lili
authors: L
authors: Cao
authors: Xiuhe
authors: X
authors: Zhao
authors: Hong
authors: H
authors: Jiang
authors: Zhaofu
authors: Z
authors: Chi
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D003652:Decanoic Acids / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology* / Q000627:therapeutic use; D004827:Epilepsy / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D006880:Hydroxy Acids / Q000494:pharmacology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010862:Pilocarpine; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D003652:Decanoic Acids; D003981:Diazoxide; D006880:Hydroxy Acids; D008315:Malondialdehyde; D018696:Neuroprotective Agents; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010862:Pilocarpine; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D051057:Proto-Oncogene Proteins c-akt; D013482:Superoxide Dismutase; D000077191:Wortmannin; C117780:mitochondrial K(ATP) channel; C052853:5-hydroxydecanoic acid