CEREBROPROTECTIVE EFFECTS OF KOLAVIRON IN RATS SUBJECTED TO BILATERAL COMMON CAROTID ARTERY OCCLUSION.

Abstract

The chemopreventive potential of kolaviron on cerebral injury induced by ischemia/reperfusion (I/R) has not been investigated. Hence, in the present study, the cerebroprotective effect of kolaviron in rat brain subjected to bilateral common carotid artery occlusion (BCCAO)-induced ischemic stroke was evaluated. Male Wistar rats weighing 200 ± 20 g were divided into six groups (24 rats/group): sham, vehicle, kolaviron-treated and quercetin-treated. Transient global ischemia was induced by bilateral occlusion of both common carotid arteries for 30 min and followed by 2 h of reperfusion. Kolaviron (50, 100 or 200 mg/kg body weight (bwt)) was orally administered to animals daily, for 7 days before ischemia/reperfusion (I/R) while pretreatment with quercetin (20 mg/kg bwt) was carried out 30 min before IR. After the period of reperfusion, animals were sacrificed and brains were excised for determination of brain weight, brain water content and infarct size. Markers of oxidative stress (activities of glutathione peroxidase, superoxide dismutase and catalase, reduced glutathione and malondialdehyde (MDA) levels), excitotoxicity (activities of glutamine synthetase and Na+/K+-ATPase), inflammation (myeloperoxidase (MPO) activity) and neurobiochemical alteration (acetylcholinesterase activity) were also evaluated. The results showed that IR caused significant decrease in the activities of acetylcholinesterase, glutathione peroxidase, superoxide dismutase, catalase and Na+/k+-ATPase but significant increases in glutamate synthetase activity, MPO activity and MDA level. In the pretreated groups with kolaviron, there was a significant (P < 0.05) amelioration of I/R provoked imbalances in biochemical indices, and brain water content. The effects elicited by kolaviron (200 mg/kg bwt) was comparable to that of quercetin (standard). The results indicated that the remarkable protection afforded by kolaviron involves increased resistance to oxidative stress, decreased excitotoxic and inflammatory tendencies and mitigation of altered acetyl cholinesterase metabolism which makes kolaviron a promising therapeutic agent in pathologies involving neurodegeneration such as stroke and dementia.