Evaluation of Preventive Role on Microanatomical Changes in Brain and Anticonvulsant Properties of Calcium Channel Blockers in Experimental Animal Models

Abstract

Background and objectives Drug-to-drug interactions and drug toxicity are among the many downsides of currently available epilepsy drugs. Many pathophysiological pathways have a role in the onset of seizures. Excess calcium entry into neuronal cells can cause the cells to depolarize, which can lead to seizures. Based on this basic knowledge, calcium channel blockers were assumed to be able to prevent seizures. The goal of this study was to see how the anti-convulsant properties of diltiazem, nimodipine, and flunarizine functioned in experimental animal models. To find out how diltiazem, nimodipine, and flunarizine work to stop animals from having seizures, three animal models were chosen: PTZ, Pilocarpine, and MES. Materials and Methods Wistar albino rats [180 - 250 grams], were selected for the research study. The Institutional Animal Ethics Committee [IAEC] approved the study proposal. Throughout the study, all national and international standard guidelines[CPCSEA] were followed. In wistar albino rats, the anticonvulsant properties of diltiazem (20 mg/kg), nimodipine (20 mg/kg), and flunarizine (10 mg/kg) were evaluated using the PTZ, Pilocarpine, and Maximal Electroshock Seizure (MES) test models. The onset, duration, number, and severity of seizures were recorded. After recording seizure parameters as per CPCSEA guidelines, experimental animals were sacrificed, and the brain tissue was preserved for antioxidant, neurotransmitter and inflammatory marker assays (one hemisection) and also for histological and immunohistochemistry evaluations (another hemisection). A "P" value of 0.05 was considered statistically significant when one-way ANOVA and its non-parametric variant were used to look at the data. Results When compared to the respective negative control groups, the drugs diltiazem, nimodipine, and flunarizine were able to increase the onset of seizures and decrease the duration, number and the scores of seizures. These findings were also comparable to those of the standard drug groups. When compared to the negative control groups, the drugs diltiazem, nimodipine, and flunarizine were able to increase the anti-oxidant enzymes (SOD, GPx, GSH, and CAT) and decrease the lipid peroxidation, having results that were comparable to the standard drugs. When compared to the corresponding standard drug groups, the test drug groups showed an increase in the neurotransmitter levels (Serotonin, DA, and GABA). However, as compared to the negative control group, the test drug groups showed lower levels of neurotransmitters (Glutamate and ACh). The experimental drugs diltiazem, nimodipine, and flunarizine showed favourable histopathological findings that were comparable to the standard drugs. Similarly, the experimental drugs diltiazem, nimodipine, and flunarizine delivered positive immunohistochemistry results that were comparable to the standard drugs. Conclusion In the PTZ, Pilocarpine, and MES models, diltiazem, nimodipine, and flunarizine significantly improved seizure parameters. In the PTZ, Pilocarpine, and MES models, diltiazem, nimodipine, and flunarizine considerably improved oxidative stress, neurotransmitter, and antiinflammatory conditions, as well as the neuroprotective favourable scores for the histopathological and immunohistochemistry evaluations.