Abdel-Aziz Asmaa Mohamed, Mohamed Ahmed Sayed Mahmoud, Abdelazem Osama, Okasha Ahmed Mohamed M, Kamel Maha Yehia
Department of Pharmacology, Faculty of Medicine, Minia University, Minya, Egypt.
Department of Histology and Cell Biology, Faculty of Medicine, Minia University, Minya, Egypt.
Toxicol Mech Methods. 2020 Sep;30(7):526-535. doi: 10.1080/15376516.2020.1774829. Epub 2020 Jun 12.
Cancer rates have been increased among women of reproductive age nowadays. Hence, many young female will be exposed to chemotherapeutic agents as cyclophosphamide (CP), carrying the hazards on female fertility. Cilostazol is a selective phosphodiesterase-3 inhibitor drug which exhibits antioxidant, anti-inflammatory, and anti-apoptotic activities. We aimed in this study to explore the possible protective effects of cilostazol against CP-induced ovarian damage in female rats. Cilostazol (10 mg/kg/day) was administered orally for 10 days in presence and absence of CP (150 mg/kg IP single dose) treatment. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen (E2), and anti-Müllerian hormone (AMH) levels were determined. Ovarian oxidative stress parameters along with inflammatory biomarkers were measured. 3,5-Cyclic adenosine monophosphate (cAMP) ovarian level was detected. Ovarian histopathological examination and caspase-3 immunohistochemical study were evaluated. CP-treated rats showed a significant increase in serum levels of FSH and LH with decreased serum E2 and AMH levels with an increase in the ovarian inflammatory and oxidative stress biomarkers besides a significant decrease in cAMP ovarian level with an evident histopathological picture of ovarian damage and a high caspase-3 immunoexpression. Cilostazol pretreatment significantly restored the distributed hormonal levels, the oxidative stress and inflammatory biomarkers to their normal levels with marked improvement in histopathological picture of ovarian damage with a significant decrease in caspase-3 immunoexpression. These data suggest that cilostazol protects against CP- induced ovarian damage, which may be related to an increase in cAMP with subsequent anti-inflammatory, antioxidant, and anti-apoptotic properties.
如今，育龄女性的癌症发病率有所上升。因此，许多年轻女性会接触到环磷酰胺（CP）等化疗药物，这对女性生育能力存在危害。西洛他唑是一种选择性磷酸二酯酶-3抑制剂药物，具有抗氧化、抗炎和抗凋亡活性。我们在本研究中的目的是探讨西洛他唑对CP诱导的雌性大鼠卵巢损伤的可能保护作用。在有和没有CP（150mg/kg腹腔注射单剂量）治疗的情况下，口服给予西洛他唑（10mg/kg/天），持续10天。测定血清卵泡刺激素（FSH）、黄体生成素（LH）、雌激素（E2）和抗苗勒管激素（AMH）水平。测量卵巢氧化应激参数以及炎症生物标志物。检测卵巢中3,5-环磷酸腺苷（cAMP）水平。评估卵巢组织病理学检查和半胱天冬酶-3免疫组织化学研究。CP处理的大鼠血清FSH和LH水平显著升高，血清E2和AMH水平降低，卵巢炎症和氧化应激生物标志物增加，此外卵巢cAMP水平显著降低，伴有明显的卵巢损伤组织病理学表现和高半胱天冬酶-3免疫表达。西洛他唑预处理显著恢复了激素水平、氧化应激和炎症生物标志物至正常水平，卵巢损伤的组织病理学表现明显改善，半胱天冬酶-3免疫表达显著降低。这些数据表明，西洛他唑可预防CP诱导的卵巢损伤，这可能与cAMP增加以及随后的抗炎、抗氧化和抗凋亡特性有关。
