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表儿茶素改善阿霉素诱导的睾丸损伤:基于生化、生殖细胞学和组织学的研究。

Apigetrin ameliorates doxorubicin prompted testicular damage: biochemical, spermatological and histological based study.

机构信息

Department of Zoology, Wildlife and Fisheries, University of Agriculture, Faisalabad, 38040, Pakistan.

Department of Animal Sciences, Quaid-I-Azam University, Islamabad, 45320, Pakistan.

出版信息

Sci Rep. 2024 Apr 20;14(1):9049. doi: 10.1038/s41598-024-59392-x.

Abstract

Doxorubicin (DOX) is a highly effective, commonly prescribed, potent anti-neoplastic drug that damages the testicular tissues and leads to infertility. Apigetrin (APG) is an important flavonoid that shows diverse biological activities. The present research was designed to evaluate the alleviative role of APG against DOX-induced testicular damages in rats. Forty-eight adult male albino rats were randomly distributed into 4 groups, control, DOX administered (3 mgkg), DOX + APG co-administered (3 mgkg of DOX; 15 mgkg of APG), and APG administered group (15 mgkg). Results of the current study indicated that DOX treatment significantly reduced the activities of superoxide dismutase (SOD), glutathione reductase (GSR), catalase (CAT) and glutathione peroxidase (GPx), while increasing the levels of malondialdehyde (MDA) and reactive oxygen species (ROS). DOX treatment also reduced the sperm count, viability, and motility. Moreover, DOX significantly increased the sperm morphological anomalies and reduced the levels of plasma testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The administration of DOX significantly increased the expressions of Bax and Caspase-3, as well as the levels of inflammatory markers. Additionally, DOX treatment significantly downregulated the expressions of steroidogenic enzymes (StAR, 3β-HSD and 17β-HSD) and Bcl-2. Furthermore, DOX administration provoked significant histopathological abnormalities in the testicular tissues. However, APG supplementation significantly reversed all the testicular damages due to its androgenic, anti-apoptotic, anti-oxidant and anti-inflammatory nature. Therefore, it is concluded that APG may prove a promising therapeutic agent to treat DOX-induced testicular damages.

摘要

多柔比星(DOX)是一种高效、常用、强效的抗肿瘤药物,会损害睾丸组织,导致不育。芹菜素(APG)是一种重要的类黄酮,具有多种生物活性。本研究旨在评估 APG 对 DOX 诱导的大鼠睾丸损伤的缓解作用。48 只成年雄性白化大鼠随机分为 4 组,对照组、DOX 给药组(3mg/kg)、DOX+APG 共给药组(3mg/kg 的 DOX;15mg/kg 的 APG)和 APG 给药组(15mg/kg)。本研究结果表明,DOX 处理显著降低了超氧化物歧化酶(SOD)、谷胱甘肽还原酶(GSR)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GPx)的活性,同时增加了丙二醛(MDA)和活性氧(ROS)的水平。DOX 处理还降低了精子计数、活力和运动能力。此外,DOX 显著增加了精子形态异常,并降低了血浆睾酮、促黄体生成素(LH)和促卵泡激素(FSH)水平。DOX 的给药显著增加了 Bax 和 Caspase-3 的表达,以及炎症标志物的水平。此外,DOX 处理显著下调了类固醇生成酶(StAR、3β-HSD 和 17β-HSD)和 Bcl-2 的表达。此外,DOX 给药引起睾丸组织明显的组织病理学异常。然而,APG 补充剂由于其雄激素、抗凋亡、抗氧化和抗炎特性,显著逆转了所有的睾丸损伤。因此,结论是 APG 可能是治疗 DOX 诱导的睾丸损伤的一种有前途的治疗剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3190/11555402/28f0c1aba529/41598_2024_59392_Fig1_HTML.jpg

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