与阿霉素诱导男性生殖功能障碍相关的嗜铁性和非嗜铁性机制。

Q1 Environmental Science
Toxicology Reports Pub Date : 2025-06-04 eCollection Date: 2025-06-01 DOI:10.1016/j.toxrep.2025.102064
E O Ajani, T M Akhigbe, P A Oyedokun, C A Adegbola, D H Adeyemi, R E Akhigbe
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引用次数: 0

摘要

尽管阿霉素作为一种化疗药物是有效的,但它对非靶器官,包括男性生殖器官具有毒性。本文综述了目前关于阿霉素(DOX)诱导男性生殖功能障碍的铁致性和非铁致性机制的证据。DOX通过诱导氧化应激、脂质过氧化、线粒体功能障碍和细胞凋亡破坏睾丸功能,特别是在间质细胞、支持细胞和生精细胞中。这些影响导致睾丸激素分泌减少,精子发生受损,精液质量差。此外,DOX改变下丘脑-垂体-性腺(HPG)轴,下调参与类固醇生成的关键酶,加剧激素失衡和不孕风险。新兴研究强调,铁依赖性细胞死亡是dox诱导睾丸损伤的主要原因,有证据表明,褪黑激素和氧化锌纳米颗粒等抗氧化剂可能具有保护作用。此外,本综述的结果揭示了研究干预策略潜力的必要性。这项研究强调了综合护理方法的必要性,优先考虑癌症管理和生育保护。本综述旨在告知医疗保健提供者、患者和决策者阿霉素治疗的重要后果,并为辅助治疗开辟新的治疗视野。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Ferroptotic- and non-ferroptotic mechanisms associated with doxorubicin-induced male reproductive dysfunction.

Despite the effectiveness of doxorubicin as a chemotherapeutic agent, it exerts toxicity on non-target organs, including the male reproductive organs. This review synthesizes current evidence on both ferroptotic and non-ferroptotic mechanisms underlying doxorubicin (DOX)-induced male reproductive dysfunction. DOX disrupts testicular function by inducing oxidative stress, lipid peroxidation, mitochondrial dysfunction, and apoptosis, particularly in Leydig, Sertoli, and spermatogenic cells. These effects result in reduced testosterone production, impaired spermatogenesis, and poor semen quality. Additionally, DOX alters the hypothalamic-pituitary-gonadal (HPG) axis and downregulates key enzymes involved in steroidogenesis, exacerbating hormonal imbalances and infertility risks. Emerging research highlights ferroptosis, iron-dependent cell death, as a major contributor to DOX-induced testicular damage, with evidence showing that antioxidant agents like melatonin and zinc oxide nanoparticles may offer protective effects. In addition, the results of this review reveal the necessity of investigating the potential of interventional strategies. This research highlights the need for integrative care approaches prioritizing cancer management and fertility preservation. This review aims to inform healthcare providers, patients, and policymakers about the significant consequences of doxorubicin therapy and open new therapeutic horizons for adjuvant therapies.

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来源期刊
Toxicology Reports
Toxicology Reports Environmental Science-Health, Toxicology and Mutagenesis
CiteScore
7.60
自引率
0.00%
发文量
228
审稿时长
11 weeks
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