EFFECTS OF KOLAVIRON ON NEUROLOGICAL DEFICIT AND BRAIN REDOX HOMEOSTASIS IN RATS SUBJECTED TO GLOBAL ISCHEMIA/REPERFUSION

Abstract

This study was designed to investigate the protective potential of kolaviron against global ischemia/reperfusion-induced brain damage in male Wistar rats. Animals which were 48 in number were divided into eight groups with 6 animals in each group. Animals in the ischemic control group received corn oil (vehicle) and were subjected to 30 min of Bilateral Common Carotid Artery Occlusion (BCCAO) followed by 4 h of reperfusion (BCCAO/R). Animals in the sham group were subjected to the same stress as the ischemic control animals but without BCCAO/R. Two groups were orally administered 100 mg/kg bwt and 200 mg/kg bwt Kolaviron dissolved in corn oil, respectively, 1 h prior to BCCAO/R. The reference group(standard) was administered 20 mg/kg bwt quercetin 30 min before BCCAO/R. Three other groups were administered 100 mg/kg bwt kolaviron, 200 mg/kg bwt kolaviron and 20 mg/kg bwt quercetin respectively but not subjected to BCCAO/R. After the period of reperfusion, neurobehavioral assessments were carried out on animals using the Zea longa and visual placement tests. Animals were sacrificed and brain cortex and striatum were excised and separately processed for biochemical estimations. Assays for ferric reducing antioxidant power (FRAP), activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase, levels of reduced glutathione (GSH), lipid peroxidation (MDA level) and total protein concentration were carried out. Results in vivo showed that neurological deficits were significantly higher in the ischemic control group compared with the sham group (p<0.05). The neurological deficits were markedly reduced in kolaviron treated groups subjected to BCCAO/R compared with the ischemic control group (p<0.05). In addition, comparison of the ischemic control and sham groups indicated that BCCAO/R caused significant (p<0.05) decrease in the activities of SOD, GPx and catalase as well as the concentration of GSH while there was a significant increase in MDA level, in both cortex and striatum. Compared with the ischemic control group, kolaviron pretreated groups subjected to BCCAO/R showed increase in GSH level and SOD, GPx and catalase activities but decrease in MDA level. Results of groups administered kolaviron without undergoing BCCAO/R were for comparable or better than values for the sham group. These results showed that pretreatment with kolaviron significantly ameliorated ischemia/reperfusion induced alterations in both enzymatic and non-enzymatic biochemical indices, enhanced the antioxidant defense against ischemia/reperfusion injury and significantly reduced the neurological deficits occasioned by ischemia/reperfusion. The demonstrated cerebroprotective property of kolaviron suggests that it could be a potential therapeutic agent for the treatment of stroke.