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The effect of mitochondrial calcium uniporter opener spermine on diazoxide against focal cerebral ischemia--reperfusion injury in rats.

BACKGROUND: Recent research has indicated that mitochondrial adenosine triphosphate-sensitive potassium channels play an important role in cerebral protection, which involves in attenuating the calcium of mitochondria. However, the effect of diazoxide on cerebral ischemia-reperfusion and the role of spermine, the agonist of mitochondrial calcium uniporter (MCU), remain unknown.

OBJECTIVE: We investigated the effect of MCU opener spermine on diazoxide against focal cerebral ischemia-reperfusion injury in rats.

METHODS: Adult male Wistar rats were randomly divided into 5 groups: the Sham group, the I/R group, the Dzx + I/R group, the Dzx + Sper + I/R group, and the Sper + I/R group. Rats were exposed to 2-hour ischemia and 24-hour reperfusion. Diazoxide were administrated 30 minutes before ischemia, and spermine were given 10 minutes before reperfusion. Rats in the Sham group did not experience the process of ischemia-reperfusion. After 24-hour reperfusion, rats were given neurological performance tests, overdosed with general anesthesia, and then their brains were excised for infarct volume, pathological changes, and biochemical evaluation and analysis.

RESULTS: Rats in the Dzx + I/R group displayed improved neurological deficits and decreased infarct volume and oxidative stress (evidenced by decreased nitric oxide and malondialdehyde but increased antioxidant enzymes [eg, glutathione peroxide and superoxide dismutase]) caused by ischemia-reperfusion. The beneficial effects of diazoxide were significantly attenuated by spermine treatment. Rats in the Sper + I/R group displayed worse neurological deficits, larger infarct volume and more oxidative stress, and less antioxidant enzymes than those in the Dzx + I/R.

CONCLUSIONS: Our results suggested that diazoxide, which improved neurological deficits and decreased infarct volume and oxidative stress against ischemia-reperfusion injury, is mediated by spermine.

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