title: 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.affiliation: Department of Anesthesiology of Liaocheng People's Hospital, The Medical College of Qingdao University, Qingdao, Shandong Province, China.
authors.forename: Huanli
authors.initials: H
authors.lastname: Dong
authors.affiliation: Department of Anesthesiology of Affiliated Hospital of Qingdao University Medical College, Qingdao, Shandong Province, China. Electronic address: wshlei@yahoo.com.cn.
authors.forename: Shilei
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology of Liaocheng People's Hospital, The Medical College of Qingdao University, Qingdao, Shandong Province, China.
authors.forename: Zongwang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology of Liaocheng People's Hospital, The Medical College of Qingdao University, Qingdao, Shandong Province, China.
authors.forename: Ailan
authors.initials: A
authors.lastname: Yu
authors.affiliation: Department of Anesthesiology of Liaocheng People's Hospital, The Medical College of Qingdao University, Qingdao, Shandong Province, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D002544:Cerebral Infarction / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D019610:Cytoprotection; D003981:Diazoxide / Q000494:pharmacology*; D004195:Disease Models, Animal; D005979:Glutathione Peroxidase / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D013096:Spermine / Q000633:toxicity*; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors
chemical_list: D015220:Calcium Channels; D018696:Neuroprotective Agents; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; C034703:mitochondrial calcium uniporter; D013096:Spermine; D009569:Nitric Oxide; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D003981:Diazoxide
keywords: Nitric oxide; antioxidative enzymes; lipid peroxidation; mitochondrial uniporter