Protective effects of sildenafil administration on chemotherapeutic-induced ovarian damage in rats

Abstract

Agents to reduce the gonadotoxic effects of chemotherapeutics are still under investigation. In this context, we aimed to investigate the protective effect of sildenafil against chemotherapeutic-induced gonadotoxicity in a rat model. A total of 62 female rats were divided into eight groups as control, sildenafil (1.4 mg/kg, orally), doxorubicin (3 mg/kg, i.p.), cisplatin (5 mg/kg, i.p.), cyclophosphamide (200 mg/kg, i.p.), doxorubicin+sildenafil, cisplatin+sildenafil, and cyclophosphamide+sildenafil (1.4 mg/kg orally sildenafil in addition to the same dose of chemotherapeutics). The groups were compared in terms of follicle count, ovarian size, and anti-müllerian hormone (AMH) levels. Use of sildenafil with cyclophosphamide was effective only in preserving primary follicle count (p = 0.026) and had no significant change in the secondary follicle count, ovarian size, or AMH level. Adding sildenafil to cisplatin had a significant protective effect on primary follicle count (p = 0.011), secondary follicle count (p = 0.009), and ovarian size (p = 0.001), but this effect could not be demonstrated at AMH level. Sildenafil was not effective on any parameter in the doxorubicin group. Sildenafil may be effective in reducing the gonadotoxicity associated with the use of cisplatin and cyclophosphamide.