Graded doses of grape seed methanol extract attenuated ataxic movement, cerebellocortical toxicity, and impairment following chronic carbamazepine treatment in male Wistar rats

Abstract

This study investigated the effects of chronic cotreatment of carbamazepine (CBZ) with grape seed methanolic extract (GSME) on the markers of neurotoxicity and motor coordination in male rats. Thirty male Wistar rats were randomized into 5 groups (n = 6) and treated orally with propylene glycol (PG 0.1 ml/day), CBZ (25 mg/kg), CBZ (25 mg/kg) + GSME (200 mg/kg), CBZ (25 mg/kg) + GSME (100 mg/kg), or CBZ (25 mg/kg) + GSME (50 mg/kg) for 28 days. Thereafter, the animals were subjected to motor-coordination tests and, eventually, sacrificed by cervical dislocation. The cranium was opened and the brain excised. The prefrontal cortex (PFC) and cerebellum were homogenized for the biochemical assessment, while representative brain was fixed in 10% neutral-buffered formalin for the histomorphological investigation. The results were presented as mean ± SEM, analyzed using one-way analysis of variance (ANOVA) and Student-Newman–Keuls post hoc analysis where appropriate, while p < 0.05 was considered statistically significant. Indices of motor coordination were significantly (p = 0.0014) impaired with a significant (p = 0.0001) increase in the concentration of malondialdehyde (MDA) in the PFC and cerebellar tissue. In addition, the activities of glutathione increased (p = 0.0001) significantly in the CBZ + GSME-treated rats. All these anomalies were attenuated in the CBZ + GSME treated rats.Coadministration of GSME with CBZ may ameliorate CBZ-induced neurotoxicity, histoarchitectural disorganization of PFC and cerebellum with resultant effect on fine motor actions.