Laboratory of Toxicology, Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Theriogenology. 2012 Aug;78(3):620-31. doi: 10.1016/j.theriogenology.2012.03.008. Epub 2012 Apr 26.
The objective was to evaluate ovarian functionality and oxidative response in hyperandrogenism-induced polycystic ovary (PCO) and the protective effects of immunomodulator drug (IMOD), an electromagnetically-treated, selenium-based, herbal medicine. Daily oral administration of letrozole (1 mg/kg) for 21 consecutive days induced ovarian cysts in female rats. An effective dose of IMOD (30 mg/kg per day) was given intraperitoneally for 21 days. Biomarkers of ovarian function, serum concentrations of estradiol, progesterone, testosterone, and ovarian prostaglandin-E (PGE), were analyzed. To determine the role of oxidative stress (OS) in hyperandrogenism-induced PCO, concentrations of cellular lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), peroxynitrite (ONOO), and tumor necrosis factor (TNF)-α as a marker of inflammation and apoptosis were measured in serum and ovaries. Letrozole-induced PCO resulted in significant increases in concentrations of lipid peroxidation and peroxynitrite in serum and ovary, but significantly decreased superoxide dismutase, catalase, and glutathione peroxidase. Serum concentrations of testosterone and TNF-α, and ovarian prostaglandin-E were increased (P < 0.001) in animals with cysts versus control, whereas estradiol and progesterone were decreased (P < 0.01 and P < 0.001, respectively). When compared with controls, letrozole induced irregular cycles and PCO characterized by a high incidence of subcapsular ovarian cysts with a diminished granulosa cell layer, luteinized granulosa cells in the cyst wall, significantly more atretic preantral and antral follicles, and absence of CL. There were almost no intact primary, secondary, and tertiary follicles in PCO rats. All end points assessed were significantly improved by IMOD and reached close to normal levels. In conclusion, the present study provided evidence that toxic free radicals and TNF-α were involved in the pathogenesis of PCO; furthermore, IMOD prevented ovarian histopathologic, endocrine, and biochemical alterations induced by hyperandrogenism.
目的在于评估在高雄性激素诱导的多囊卵巢（PCO）中卵巢功能和氧化反应，并评估免疫调节剂药物（IMOD）的保护作用，IMOD 是一种经过电磁场处理的、基于硒的草药。连续 21 天每天口服来曲唑（1mg/kg）诱导雌性大鼠卵巢囊肿。腹腔内给予有效剂量的 IMOD（30mg/kg/天）21 天。分析卵巢功能的生物标志物、血清雌二醇、孕酮、睾酮和卵巢前列腺素-E（PGE）浓度。为了确定氧化应激（OS）在高雄性激素诱导的 PCO 中的作用，测量血清和卵巢中细胞脂质过氧化（LPO）、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GPx）、过氧亚硝酸盐（ONOO）和肿瘤坏死因子（TNF）-α的浓度作为炎症和细胞凋亡的标志物。来曲唑诱导的 PCO 导致血清和卵巢中脂质过氧化和过氧亚硝酸盐浓度显著增加，但 SOD、CAT 和 GPx 显著减少。与对照组相比，患有囊肿的动物的血清睾酮和 TNF-α以及卵巢前列腺素-E 浓度增加（P<0.001），而雌二醇和孕酮浓度降低（分别为 P<0.01 和 P<0.001）。与对照组相比，来曲唑诱导不规则周期和 PCO，其特征是包膜下卵巢囊肿的高发生率，颗粒细胞层减少，囊壁中黄体化颗粒细胞，明显更多的闭锁前和窦前卵泡，并且没有 CL。PCO 大鼠中几乎没有完整的初级、次级和三级卵泡。IMOD 显著改善了所有评估终点，使其接近正常水平。总之，本研究提供了证据表明，有毒自由基和 TNF-α参与了 PCO 的发病机制；此外，IMOD 可预防高雄性激素引起的卵巢组织病理学、内分泌和生化改变。
