阿霉素诱导的睾丸毒性:实验模型中可能的潜在机制和有希望的药理学治疗。

Shorouk A Alafifi, S. Wahdan, D. Elsherbiny, S. Azab
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引用次数: 0

摘要

化疗被认为是癌症治疗中最有效的干预手段。第一次使用化疗开始于20世纪40年代,不幸的是,它的使用导致许多严重和衰弱的副作用,影响人类的日常活动。阿霉素是一种强大的抗肿瘤药物,fda批准用于多种癌症类型的治疗,包括白血病和淋巴瘤。然而,由于其对不同组织的毒性作用,包括睾丸毒性,对癌症幸存者的生活质量产生不良影响,其临床应用受到限制。dox诱导的睾丸毒性除了影响甾体生成外,还伴随着精子分析缺陷,包括精子数量低、精子活力低和精子高度异常。本文旨在讨论阿霉素的药效学和药代动力学,以及可能导致DOX引起睾丸损伤的潜在机制,包括氧化应激、炎症、细胞凋亡和自噬。此外,还讨论了动物化疗后睾丸毒性的评估以及在动物模型中研究的有前景的药物治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Doxorubicin-induced testicular toxicity: possible underlying mechanisms and promising pharmacological treatments in experimental models.
Chemotherapy is considered to be the most effective intervention in cancer treatment. The first use of chemotherapy began in the 1940s, unfortunately, its use result in many serious and debilitating side effects which affect human daily activities. Doxorubicin is a powerful antineoplastic drug FDA-approved for the management of a variety of cancer types including leukemia and lymphoma. However, its clinical use is limited due to its toxic effect on different tissues including testicular toxicity which has a bad impact on the quality of life of cancer survivors. DOX-induced testicular toxicity is accompanied by defects in sperm analysis including low sperm count, low sperm motility, and high sperm abnormalities in addition to affecting steroidogenesis. This review is intended to discuss the pharmacodynamics and the pharmacokinetics of doxorubicin, besides the possible underlying mechanisms that may be contributed to the damage of testicles caused by DOX including oxidative stress, inflammation, apoptosis, and autophagy. Moreover, the assessment of post-chemotherapy testicular toxicity in animals and the promising pharmacological treatment that has been studied in animal models were discussed.
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