Effect of Calcium Channel Blockers on the Seizures, Oxidative Stress, and Histoarchitecture in the Rats

Abstract

Objective: To evaluate the anticonvulsant and antioxidant actions of diltiazem, nimodipine, and flunarizine in the Wistar albino rats using the maximum electroshock‑induced seizure (MES) model.Materials and Methods: Thirty inbred Wistar rats were divided into five groups of six rats in each group. Groups 3, 4, and 5 were pretreated with diltiazem (20 mg/kg), nimodipine (20 mg/kg), and flunarizine (10 mg/ kg), respectively. Group 2 served as a standard group and received phenytoin (25 mg/kg). All groups were subjected to MES. Twenty‑four hours after the MES, hemisections of the rat brain were homogenized, and oxidative markers (glutathione [GSH], lipid peroxidation [LPO], and myeloperoxidase [MPO]) and neurotransmitters (dopamine, serotonin, gamma‑aminobutyric acid, acetylcholine, and glutamate levels) were estimated. Histological changes were studied with hematoxylin and eosin‑stained hemisection of rat brain. Apoptotic marker heat shock protein (HSP) was used for immunohistochemical changes.Results: Rats pretreated with diltiazem, nimodipine, and flunarizine showed a statistically significant reduction in duration of hind limb extension phase and clonic seizures. GSH, LPO, and MPO changes indicate better oxidative stress outcomes in rat brains pretreated with diltiazem and flunarizine. Neurotransmitters showed variable and significant changes. There were histoarchitectural changes such as cerebral edema, vacuole formation, and intracytoplasmic granules with all three calcium channel blockers in acute phase. HSP was positive in temporal lobe sections of rats pretreated with nimodipine.Conclusions: Diltiazem, nimodipine, and flunarizine showed an anticonvulsant action among Wistar rats in MES model. Diltiazem and flunarizine have antioxidant actions as well.

Keywords: Antiseizure; calcium channel blockers; histology; maximum electroshock-induced seizure model; neurotransmitters; oxidative stress