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Investigation of the Effects of Chronic Use of Zonisamide, Sultiam, Lacosamide, Clobazam and Rufinamide Antiepileptic Drugs on Foliculogenesis in Ovarian Tissue in Prepubertal Non-Epileptic Rats

Objectives: In our study, we aimed to examine the apoptotic and immunohistochemical damage to the ovarian tissue caused by the use of new and old generation anti-seizures medication (ASMs) in prepubertal non-epileptic rats. Methods: In our experimental study, 21–24-day-old prepubertal Wistar rats were used. Six groups were determined in groups of ten. ASMs and control solution were applied by gavage every 12 hours for ninety days. No rats were excluded from the study. The rats in the oestrus cycle were sacrificed, and their ovarian tissues were placed in formalin solution. Immunohistochemical and apoptosis (TUNEL) protocols were applied. Results: While the number of healthy follicles in the control group was found to be significantly higher, the number of corpus luteum was found to be significantly lower (p<0.001; Table 1; Figure-1). The number of TUNEL positive apoptotic follicles was statistically significantly higher in the zonisamide, sultiam, and clobazam groups (p<0.001) Table 1). TUNEL positive granulosa cells were found to be significantly higher in the ASM group (p<0.001). GDF-9 (Growth Differentiation Factor-9), EGF (Epidermal growth factor), IGF-1 (Insulin-like growth factor-1) immunohistochemical labeling was observed in the ovarian multilaminar primary follicle granulosa cells of the control group, while a very strong immunoreaction was observed in the ASM groups, and it varied from weak to medium. immunoreaction was observed ((p < 0.001; Table 2; Figure-2). Conclusion: Zonizamide, sultiam, lacosamide, clobazam, and rufinamide, used long-term from prepuberty to adulthood, cause apoptosis and disruption of folliculogenesis in rat ovarian follicles.
Keywords: Antiepileptic, EGF, GDF-9, IGF-1, Ovary