Effect of Cyclooxygenase Inhibitors on Neurological and Oxidative Damage in Experimentally Induced Acute Cerebral Ischemia/Reperfusion In Rats

Background: Neuroinflammation is one of the key pathological events involved in the progression of brain damage caused by cerebral ischemia. Metabolism of arachidonic acid through cyclooxygenase (COX) enzymes are involved in neuroinflammation events.Aim of the Work: The purpose of this study was to detemine whether the COX inhibitors, indomethacin (5mg/kg/IP), valeryl salicylate (VAS) (20mg/kg/IP) andnimesulide (12mg/kg/IP) could effectively ameliorate neurological and oxidative damage induced in animal model of cerebral ischemia in rat.Material and Methods: Cerebral ischemia was induced by occlusion of left common carotid artery for 60min, stroke index was calculated. Behavioral tests were performed. Rats were sacrificed then, malondialdyhyde (MDA), glutathione peroxidase (GHPx) superoxide dismutase (SOD) and areas of cerebral infarction were measured.Results: Treatment immediately after ischemia with nimesulide and indomethacin significantly reduced the infarct size and improved neurological deficit. While VAS has no effect, nimesulide only significantly decreased lipid peroxidation measured as MDA and a significant increase GHPx and SOD. In the same time, indomethacin and VAS have no effect on these measures.Conclusion: The interest is the findings that nimesulide (COX2 inhibitor) indomethacin (non selective COX inhibitor) have early therapeutic effect against cerebral ischemia. The antioxidant effect may be one of the mechanisms of both drugs which appears significantly in nemisulide only, rather non selective COX. This is may be due to the action of indomethacin on COX1 beside COX2 which has confounding effects resulting from COX1 inhibition and masks its action as antioxidant or through other mediators. ROS play a pathogenic role in ischemic injury but we cannot rule out the participation of other mediators or other sources of ROS that contribute and support the hypothesis that other components beside oxygen radical are determinants of ischemic brain death. This components as vascular reactivity, non oxygen based radical, inflammatory mediators and glutamate receptor.