Nebivolol regulates eNOS and iNOS expressions and alleviates oxidative stress in cerebral ischemia/reperfusion injury in rats.
OBJECTIVE
Oxidative stress-induced cell damage is reported to contribute to the pathogenesis of cerebral ischemia/reperfusion injury. This study investigated the neuroprotective effect of nebivolol against cerebral ischemia/reperfusion insult in rats.


METHODS
The model adopted was that of surgically-induced forebrain ischemia, performed by means of bilateral common carotid artery occlusion for 1h, followed by reperfusion for 24 h. The effects of 5 and 10 mg/kg nebivolol, treated for 7 days prior to ischemia/reperfusion insult, were investigated by estimating endothelial and inducible nitric oxide synthases (eNOS and iNOS) protein expressions and assessing oxidative stress-related biochemical parameters in the rat forebrain. Also, infarct volume measurement and histopathological study of the forebrain were examined.


RESULTS
Administration of nebivolol increased eNOS expression with simultaneous decrease in iNOS expression in a dose dependent manner. Moreover, nebivolol inhibited ischemia/reperfusion-induced depletion of reduced glutathione level and decreased the elevated total nitric oxide end production and malondialdehyde levels, superoxide dismutase and lactate dehydrogenase activities. A notable finding is that catalase activity was not changed in response to either ischemia/reperfusion insult or nebivolol treatment. However, the results confirmed that nebivolol significantly reduced infarct volume and alleviated ischemia/reperfusion-induced histopathological changes.


CONCLUSIONS
The present study demonstrates the neuroprotective effect of nebivolol against cerebral ischemia/reperfusion insult. Neuroprotection observed with nebivolol may possibly be explained by regulating eNOS and iNOS expressions and by inhibition of oxidative stress-induced injury. Thus, nebivolol may be considered as a potential candidate for treatment in patients who are prone to stroke.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, El-Minia, Egypt. ghhh70@yahoo.com
Gehan H
GH
Heeba
Amr A
AA
El-Hanafy
D000704:Analysis of Variance; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology* / Q000627:therapeutic use; D015153:Blotting, Western; D002374:Catalase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000494:pharmacology* / Q000627:therapeutic use; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D000068577:Nebivolol; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D016548:Prosencephalon / Q000187:drug effects / Q000473:pathology*; D051381:Rats; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D013778:Tetrazolium Salts
D001578:Benzopyrans; D004983:Ethanolamines; D018696:Neuroprotective Agents; D013778:Tetrazolium Salts; D000068577:Nebivolol; C009591:triphenyltetrazolium; D002374:Catalase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat