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

Abstract

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.

• Authors: Huanli Dong, Shilei Wang, Zongwang Zhang, Ailan Yu, Zhong Liu
• Journal: Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association (J Stroke Cerebrovasc Dis) Vol. 23 Issue 2 Pg. 303-9 (Feb 2014) ISSN: 1532-8511 [Electronic] United States
• PMID: 23540254 (Publication Type: Journal Article)
• Copyright: Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Chemical References

• Calcium Channels
• Neuroprotective Agents
• Potassium Channels
• mitochondrial K(ATP) channel
• mitochondrial calcium uniporter
• Spermine
• Nitric Oxide
• Malondialdehyde
• Glutathione Peroxidase
• Superoxide Dismutase
• Diazoxide

Topics

• Animals
• Behavior, Animal (drug effects)
• Brain (drug effects, metabolism, pathology, physiopathology)
• Calcium Channels (drug effects, metabolism)
• Cerebral Infarction (diagnosis, metabolism, pathology, physiopathology, prevention & control)
• Cytoprotection
• Diazoxide (pharmacology)
• Disease Models, Animal
• Glutathione Peroxidase (metabolism)
• Male
• Malondialdehyde (metabolism)
• Mitochondria (drug effects, metabolism)
• Motor Activity (drug effects)
• Neuroprotective Agents (pharmacology)
• Nitric Oxide (metabolism)
• Oxidative Stress (drug effects)
• Potassium Channels (drug effects, metabolism)
• Rats
• Rats, Wistar
• Reperfusion Injury (diagnosis, metabolism, pathology, physiopathology, prevention & control)
• Spermine (toxicity)
• Superoxide Dismutase (metabolism)
• Time Factors