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

• Published in: International journal of developmental neuroscience
• Main Authors: Kart, Pınar Özkan, Gürgen, Seren Gülşen, Esenülkü, Gülnur, Dilber, Beril, Yıldız, Nihal, Yazar, Uğur, Sarsmaz, Hayrunnisa Yeşil, Topsakal, Ali Samet, Kamaşak, Tülay, Arslan, Elif Acar, Şahin, Sevim, Cansu, Ali
• Format: Journal Article
• Language: English
• Published: United States 09-06-2022
• Subjects: Ovary; EGF; Epilepsy; Antiepileptic; IGF-1; GDF-9; Apoptosis
• ISSN: 1873-474X

We aimed to determine the morphological and histological effects of zonisamide, sultiam, lacosamide, clobazam, and rufinamide on ovarian folliculogenesis in rats. Sixty female Wistar rats were equally divided into 6 experimental groups, including control group, zonisamide, sultiam, lacosamide, clobazam, and rufinamide were administered by gavage for 90 days. According to the daily vaginal smears of the rats in the proestrus and diester phases of the estrus cycle, their ovaries were removed and placed in the fixation solution. Immunohistochemical and apoptosis staining protocols were applied. The number of healthy follicles in the control group was found to be statistically significantly higher when compared to the antiseizure drug groups (p<0.001). The number of corpus luteum was found to be statistically significantly lower in the control group when compared with the anti-seizure drug groups (p<0.001). There was a significant difference in the number of TUNEL positive apoptotic follicles between the control and drug groups (p<0.001). There was a significant difference in the number of TUNEL positive apoptotic follicles between the control and drug groups (p<0.001). HSCORE, immunohistochemical EGF, IGF-1 and GDF-9 staining, a very strong immunoreaction was observed in the ovarian multilaminar primary follicle granulosa cells and oocytes in the control group (p<0.001), and an immunoreaction ranging from weak to medium was observed in the antiseizure drug groups. Long-term anti-seizure drug therapy with zonisamide, sultiam, lacosamide, clobazam, and rufinamide from prepubertal to adulthood causes apoptosis and disruption of folliculogenesis in the ovarian follicles of nonepileptic rats.