Hesperidin pre-treatment attenuates NO-mediated cerebral ischemic reperfusion injury and memory dysfunction

Abstract

The present study was designed to explore the mechanism of hesperidin action via the nitric oxide pathway in the protection against ischemic reperfusion cerebral injury-induced memory dysfunction. Male Wistar rats (200–220g) were subjected to bilateral carotid artery occlusion for 30min followed by 24h reperfusion. Hesperidin (50 and 100mg/kg,po) pretreatment was given for 7days before animals were subjected to cerebral I/R injury. Various behavioral tests (rotarod performance and memory retention), biochemical parameters (lipid peroxidation, nitrite concentration, glutathione levels, superoxide dismutase activity and catalase activity), mitochondrial complex enzyme dysfunctions (complex I, II, III and IV) and histopathological alterations were subsequently assessed in hippocampus. Seven days of hesperidin (50 and 100mg/kg) treatment significantly improved neurobehavioral alterations (delayed fall off time and increased memory retention), oxidative defense and mitochondrial complex enzyme activities in hippocampus compared to control (I/R) animals. In addition, hesperidin treatment significantly attenuated histopathological alterations compared to control (I/R) animals. L-arginine (100mg/kg) pretreatment attenuated the protective effect of the lower dose of hesperidin on memory behavior, biochemical and mitochondrial dysfunction compared with hesperidin alone. However, L-NAME pretreatment significantly potentiated the protective effect of hesperidin. The present study suggests that the L-arginine-NO signaling pathway is involved in the protective effect of hesperidin against cerebral I/R-induced memory dysfunction and biochemical alterations in rats.