European Journal of Pharmacology, 2016, 789:163-171.

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

Dalia O Saleh, Dina F Mansour

Pharmacology Department, National Research Centre, 33 EL Bohouth St. (former EL Tahrir St.), P.O. 12622, Dokki, Giza, Egypt

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-müllerian hormone (AMH) and oestradiol (E2) were detected as well as the ovarian level of reduced glutathione (GSH), activity of superoxide dismutase (SOD), level of malondialdehyde (MDA) and interleukin 1β (IL-1β) 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 E2 and elevating oxidative stress and inflammation in ovarian tissues. Histologically, 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 E2 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.

荷兰《欧洲药理学杂志》, 2016, 789:163-171.

金雀异黄素对环磷酰胺中毒大鼠的卵巢保护效果︰ 抗苗勒激素和雌二醇的作用

Dalia O Saleh, Dina F Mansour

药学系，国家研究中心，33 EL Bohouth 圣 （前埃塔利尔圣），P.O.12622，Dokki，吉萨埃及

环磷酰胺（CP），癌症治疗中常用的化疗剂，被证明导致妇女的卵巢毒性和不育。在本研究中，我们调查了大豆蛋白中发现的植物雌激素（GEN）对大鼠中CP诱导的卵巢毒性的保护作用。将四十只雌性成年大鼠分成五组。正常对照组使用赋形剂;另一组注射单次急性腹膜内剂量的CP（200mg/kg）。另三组用GEN（0.5、1、2mg/kg;皮下）预处理14天。在CP治疗后48小时获得血清和卵巢。检测抗米勒激素（AMH）和雌二醇（E2）的血清水平以及还原型谷胱甘肽（GSH），超氧化物歧化酶（SOD）活性，丙二醛（MDA）水平和白细胞介素1β（IL- 1β）。进行诱导型一氧化氮合成酶（iNOS）的组织病理学检查和免疫组织化学检测。本研究的结果表明CP诱导严重卵巢毒性通过减少AMH和E2的血清水平和升高氧化应激和卵巢组织炎症。组织学上，CP导致原始卵泡增加，卵巢组织中较少的卵泡和黄体以及严重诱导iNOS。与CP处理组相比，GEN抑制血清AMH和E2的严重降低，同时缓解氧化应激和炎症。 GEN改善了通过CP破坏的卵巢iNOS的卵巢组织学和免疫染色。最后，可以得出结论，GEN对CP诱导的卵巢毒性发挥保护作用。