Department of Histology and Embryology, Faculty of Medicine, Erciyes University, Kayseri, Turkey.
Department of Pharmaceutical Basic Science, Faculty of Pharmacy, Erciyes University, Kayseri, Turkey.
J Biochem Mol Toxicol. 2024 Jan;38(1):e23522. doi: 10.1002/jbt.23522. Epub 2023 Aug 31.
Doxorubicin (Dox) may induce loss of follicles, resulting in the depletion of ovarian reserve and consequent premature ovarian failure. Selenium (Se) is an oligoelement with fundamental biological features and is among the most common chemical inhibitor compounds. The present study describes the curative effects of dietary supplementation with different Se doses on Dox-induced ovarian damage in rats. In this study, 64 adult female Wistar rats were randomly separated into eight groups: Control group, Dox group (5 mg/kg intraperitoneal [i.p.]), low-dose Se (0.5 mg/kg i.p.), middle dose Se (1 mg/kg i.p.), high dose (Se 2 mg/kg i.p.), Dox + low-dose Se group (0.5 mg/kg i.p.), Dox + middle dose Se (1 mg/kg i.p.), and Dox + high-dose Se group (2 mg/kg i.p.). After the experiment, ovarian follicles were counted, and Antimüllerian hormone, interleukin 1 beta, tumor necrosis factor alpha, and caspase-3 expression were determined. Levels of malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase were biochemically measured in ovarian tissue. Dox caused ovarian injury, as evidenced by significant changes in ovarian markers, histological abnormalities, and the debilitation of antioxidant defense mechanisms. Furthermore, Dox therapy significantly changed the expression of inflammatory and apoptotic markers. Dox + 1 mg Se with various saturations was studied, and this study demonstrated both histopathological and follicular reserve and more protective features. 1 mg Se pretreatment improved Dox-induced ovarian toxicity through alleviating the antioxidant mechanism, decreasing inflammation and apoptosis, and restoring ovarian architecture. As a result, our findings indicate that 1 mg Se is a promising therapeutic agent for the prevention of ovarian damage associated with Dox.
多柔比星(Dox)可能导致卵泡丧失,导致卵巢储备耗竭,进而导致卵巢早衰。硒(Se)是一种具有基本生物学特征的微量元素,是最常见的化学抑制剂化合物之一。本研究描述了不同硒剂量的饮食补充对大鼠多柔比星诱导的卵巢损伤的治疗效果。在这项研究中,将 64 只成年雌性 Wistar 大鼠随机分为八组:对照组、多柔比星组(5mg/kg 腹腔内[ip])、低剂量硒组(0.5mg/kg ip)、中剂量硒组(1mg/kg ip)、高剂量硒组(2mg/kg ip)、多柔比星+低剂量硒组(0.5mg/kg ip)、多柔比星+中剂量硒组(1mg/kg ip)和多柔比星+高剂量硒组(2mg/kg ip)。实验结束后,计数卵巢卵泡,并测定抗苗勒管激素、白细胞介素 1β、肿瘤坏死因子α和半胱天冬酶-3 的表达。测定卵巢组织中丙二醛、超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶的水平。多柔比星导致卵巢损伤,表现为卵巢标志物显著变化、组织学异常和抗氧化防御机制减弱。此外,多柔比星治疗显著改变了炎症和凋亡标志物的表达。研究了不同饱和度的多柔比星+1mgSe,该研究表明具有组织病理学和卵泡储备的更多保护特征。1mgSe 预处理通过减轻抗氧化机制、减少炎症和凋亡以及恢复卵巢结构来改善多柔比星引起的卵巢毒性。因此,我们的研究结果表明,1mgSe 是预防与多柔比星相关的卵巢损伤的一种有前途的治疗药物。