Neuroprotective and Anticonvulsant Effects of Sinomenine in Kainate Rat Model of Temporal Lobe Epilepsy: Involvement of Oxidative Stress, Inflammation and Pyroptosis Publisher Pubmed



Ramazi S^{1, 2} ; Fahanikbabaei J^{3, 4} ; Mohamadizarch SM¹ ; Tashakorimiyanroudi M¹ ; Nourabadi D¹ ; Nazariserenjeh M¹ ; Roghani M⁵ ; Baluchnejadmojarad T^{2, 6} Show Affiliations
Source: Journal of Chemical Neuroanatomy Published:2020

Abstract

Oxidative stress, inflammation and pyroptosis are three of the most important mechanisms in the pathophysiology of temporal lobe epilepsy (TLE). Most people with TLE are refractory to the existing drugs. Sinomenine has shown neuroprotective effects through counteracting oxidative stress, inflammation and pyroptosis. In this study, we evaluated the effect of sinomenine on seizure behavior, oxidative stress, inflammation and pyroptosis markers in addition to its neuroprotective potential in intrahippocampal kainate-induced rat model of TLE. For this purpose, male rats (n = 60) were randomly divided into five groups, i.e., sham, kainate (lesion) with an intrahippocampal injection of kainate, kainate groups receiving sinomenine at doses of 30 or 50 mg/kg, and kainate group receiving valproic acid at a dose of 200 mg/kg (as the positive control). Our obtained data showed that sinomenine administration at a dose of 50 mg/kg can significantly decreases severity of seizures and incidence of status epilepticus (SE), hippocampal aberrant MFS and DNA fragmentation and prevents reduction of neuronal density. It also significantly restored level of ROS, MDA, HO-1 and SOD but its effect on GSH level was not significant. Additionally, sinomenine at a dose of 50 mg/kg partially counteracted the increase of NF-κB, TLR 4, TNFα, GFAP and caspase 1. These results suggest that sinomenine has anticonvulsant and neuroprotective effects by reducing hippocampal oxidative stress, inflammation, pyroptosis and apoptosis in intrahippocampal kainate model of TLE. © 2020 Elsevier B.V.