CHEMOTHERAPEUTIC AGENT-INDUCED OVARIAN GONADOTOXICITY

Abstract

Paclitaxel and Carboplatin have been considered as a combined chemotherapy agents for a variety of human tumors, including ovarian carcinomas. The objective of this study was to evaluate the ovarian toxicity of two chemotherapy agents either solely or in combination against the ovarian follicular reserve in young female rats. Administration of paclitaxel and/or carboplatin significantly reduced the levels of serum gonadotropin and steroid hormones and increased ovarian MDA concentration. Activities of SOD and Catalase were significantly (P< 0.001) reduced by the combined effects of anticancer drug. The percentage of ovarian DNA fragmentation was elevated after the treatment with paclitaxel and carboplatin, when it compared with the control and other treated groups a significant (p< 00.001) fragmentation was reported in the combined treated group. The numbers of healthy follicles per ovary were decreased and the numbers of atretic follicles were increased. Histologically, the ovaries of the treated groups were hypoplastic and characterized by atresia and follicular degeneration. The mechanism of ovotoxicity involves lowering levels of pituitary gonadotrophin secretion and production of oxygen free radicals that in turn related to a decreased number of healthy follicles and increased number of atretic follicles.