Ovario-protective effects of genistein against cyclophosphamide toxicity in rats: Role of anti-miillerian hormone and oestradiol

Cyclophosphamide (CP), the commonly used chemotherapeutic agent in cancer treatment, is proven to cause ovarian toxicity and infertility in women. In the present study, we investigated the protective effect of genistein (GEN), a phytoestrogen found in the soy protein, against CP-induced ovarian toxicity in rats. Forty female adult rats were allocated into five groups. A normal control group received the vehicle; another group was injected with a single acute intraperitoneal dose of CP (200 mg/kg). Three other groups were pretreated with GEN (0.5, 1 or 2 mg/kg; s.c.) for 14 days. Sera and ovaries were obtained 48 h after CP treatment. Serum levels of anti-mullerian hormone (AMH) and oestradiol (E-2) were detected as well as the ovarian level of reduced glutathione (GSH), activity of superoxide dismutase (SOD), level of malondialdehyde (MDA) and interleukin 113 (IL-1 beta) were evaluated. Histopathological examination and immunohistochemical detection of inducible nitric oxide synthetase (iNOS) were conducted. Results of the present study revealed that CP-induced severe ovarian toxicity via decreasing serum levels of AMH and E-2 and elevating oxidative stress and inflammation in ovarian tissues. Histo-logically, CP caused increase in primordial follicles with less graafian follicles and corpora lutea in ovarian tissues as well as severe induction of iNOS. GEN inhibited the severe decrease in serum AMH and E-2 with alleviation of oxidative stress and inflammation significantly compared to CP-treated group. GEN improved ovarian histology and immunostaining of ovarian iNOS disrupted by CP. Finally, it can be concluded that GEN exerted protective effects against CP-induced ovarian toxicity. (C) 2016 Elsevier B.V. All rights reserved.