Single-dose ebselen does not afford sustained neuroprotection to rats subjected to severe focal cerebral ischemia

European Journal of Pharmacology
J B SalomE Alborch

Abstract

Oxygen free radicals have been involved in the pathophysiology of cerebral ischemia, especially after spontaneous or thrombolytic reperfusion. In this study with rats, we have combined a severe focal ischemic insult (2 h) and a prolonged reperfusion time (7 days) to assess the possible sustained neuroprotective effect of ebselen (10 or 100 mg/kg), a small, lipophilic organoselenium compound which mimics glutathione peroxidase. Parietal cortical perfusion was measured by laser-Doppler flowmetry, and focal cerebral ischemia was carried out by the intraluminal thread method. We have measured plasma selenium levels, brain reduced glutathione levels, as a marker of oxidative stress, and infarct volume associated with cerebral ischemia. Focal ischemia did not alter reduced glutathione levels, while 60 min reperfusion following ischemia induced a significant (P < 0.05) decrease in reduced glutathione levels of the ipsilateral hemisphere. Pretreatment with ebselen, which induced significant (P < 0.05) increase in plasma selenium levels, did not significantly alter the decrease in reduced glutathione levels. The ischemic insult induced 30% mortality on average, with deaths always occurring within 12-48 h. Surviving rats suffered up to 2...Continue Reading

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Citations

Jul 2, 2011·Archives of Toxicology·Cristina W Nogueira, João B T Rocha
May 16, 2006·Chemical Research in Toxicology·Honglian ShiKe Jian Liu
Feb 14, 2012·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Jade B AitkenGregory I Giles
Dec 20, 2011·Toxicology and Applied Pharmacology·A P Marreilha Dos SantosM Camila Batoreu
Mar 2, 2010·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Sanser GulBektaş Acikgoz
Mar 1, 2008·Neuropharmacology·Myron D Ginsberg
Jul 19, 2006·Drug Discovery Today·A Richard Green, Ashfaq Shuaib
Jul 27, 2005·Free Radical Biology & Medicine·Isabelle MargaillDominique Lerouet
Sep 10, 2014·Pharmacology & Therapeutics·Antonio MorettiRoberto F Villa
Feb 14, 2007·Alcoholism, Clinical and Experimental Research·Siv Johnsen-SorianoFrancisco J Romero
Mar 22, 2018·Frontiers in Microbiology·Anjan DebnathJames H McKerrow
Nov 24, 2020·Future Medicinal Chemistry·Jun WangLili Zou

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