Investigation of the effect of zonisamide in alcohol-induced neurotoxicity

Aim: This study aimed to evaluate the neuroprotective effects of zonisamide against alcohol-induced neurotoxicity. Focusing particularly on alcohol-related damage in the hippocampus, it examined how zonisamide influences the cellular and molecular changes occurring within this critical region. Materials and Methods: With approval from Dicle University, a total of 40 male Wistar albino rats were divided into four groups: one sham group and three experimental groups. The experimental groups received daily oral administration of zonisamide at a dose of 100 mg/kg, and ethanol was administered three times daily for four days according to the Majchrowicz binge alcohol protocol. After the experimental period, brain tissues were fixed in formalin, embedded in paraffin, and sectioned with a microtome. These sections were evaluated histopathologically using Hematoxylin-Eosin staining and immunohistochemically using IBA-1, pCREB, and DCX antibodies. Results: Immunohistochemical analyses revealed a protective effect of zonisamide against alcohol-induced neurodegeneration. The IBA-1 staining indicated reduced microglial activation in the zonisamide-treated groups. While pCREB levels were decreased in the alcohol-treated control group, these levels returned to normal in the zonisamide-treated rats, suggesting that the drug helps maintain neuronal function. Additionally, increased DCX expression in the zonisamide-treated groups suggests that the compound not only preserves cellular integrity but also supports neurogenic processes. Conclusion: This study clearly demonstrates the neuroprotective properties of zonisamide against alcohol-induced hippocampal neurotoxicity. The findings suggest that zonisamide may be a promising agent in the treatment of alcohol dependence, effectively preventing and reversing hippocampal damage. These results lay a solid foundation for further clinical research and the development of new therapeutic approaches to combat alcohol-related brain injury.