Abstract

Topiramate (TPM), a widely used anticonvulsant, has been documented to induce testicular dysfunction through its pro-oxidant properties, leading to cellular damage and hormonal abnormalities in the testes. This damage is characterized by increased malondialdehyde (MDA) levels and decreased activity of antioxidant enzymes such as catalase (CAT) and superoxide dismutase (SOD), which are essential for reducing oxidative stress. This study aimed to evaluate the effects of TPM and Gallic Acid (GA) on reproductive health in male rats. Forty mature Sprague-Dawley rats, aged 16 to 18 weeks and weighing between 180 and 200 g, were divided into four experimental groups (10 rats each): a control group, a TPM-treated group, a TPM + GA-treated group, and a GA-only group. The rats received TPM (18 mg/kg) orally for 60 days, with or without GA (50 mg/kg) administered orally for the same period. Testicular tissues were examined for oxidative stress markers (MDA, SOD, CAT), sperm motility, hormonal concentrations (Testosterone, gonadotropin-releasing hormone [GnRH], and 17β-hydroxysteroid dehydrogenase type 3 [17β-HSD3]), and histological changes. The results showed that TPM significantly increased MDA levels while decreasing CAT and SOD activity, indicating oxidative stress compared to the control group. Sperm motility was also impaired in the TPM-treated group. However, GA treatment led to a notable reduction in MDA levels and restored antioxidant enzyme activity toward normal levels. Hormonal analysis revealed that TPM affected testosterone and GnRH levels, although GA partially mitigated these changes. Immunohistochemical and histological assessments demonstrated considerable testicular damage in the TPM group, whereas the GA-treated group showed slight improvements in testicular histopathology and reduced cellular death. In conclusion, GA (50 mg/kg) exhibited a protective effect against TPM-induced testicular dysfunction.