Eugenol Nanoparticles Ameliorate Doxorubicin-Induced Spermatogenic Dysfunction by Inhibiting the PINK1/Parkin and BNIP3/NIX Signaling Pathways.

IF 6.5 2区医学 Q1 NANOSCIENCE & NANOTECHNOLOGY International Journal of Nanomedicine Pub Date : 2024-12-10 eCollection Date: 2024-01-01 DOI:10.2147/IJN.S494056

Yang Fu, Peipei Yuan, Manyv Wang, Yajuan Zheng, Yan Zhang, Lirui Zhao, Qingyun Ma, Pengsheng Wang, Xiaotian Sun, Xiaoke Zheng, Weisheng Feng

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Abstract

Purpose: Doxorubicin (DOX) precipitates cell apoptosis in testicular tissues, and it is imperative to develop drugs to alleviate the spermatogenic disorders it causes. Eugenia caryophyllata Thunb is often used to treat male sexual disorders. Eugenol, a major component of Eugenia caryophyllata Thunb. has inadequate stability and low solubility, which limits its pharmacological effects. Eugenol nanoparticles (NPs) (ENPs) are expected to overcome these limitations. The protective effects of ENPs against DOX-induced reproductive toxicity were studied in mice.

Methods: Eugenol was encapsulated in Methoxy-Poly(ethylene glycol)-Poly(lactide-co-glycolide) nanoparticles (mPEG-PLGA-NPs), and their role in ameliorating spermatogenic dysfunction was verified in vivo and in vitro.

Results: We present a promising delivery system that encapsulates eugenol into mPEG-PLGA-NPs and forms them into nanocomposites. In vitro, ENPs significantly reduced doxorubicin-induced ROS and inflammatory factors in GC-1 cells and regulated the expression of the mitochondrial autophagy protein PINK1 and meiosis-related protein SCP3. In vivo, ENPs significantly increased sperm motility in mice, reduced apoptosis and oxidative stress in the testes, inhibited the testicular PINK1/Parkin and BNIP3/NIX signaling pathways, and enhanced the expression of factors associated with meiosis.

Conclusion: Given their safety and efficacy, these ENPs have potential application prospects in mitigating doxorubicin-induced spermatogenic dysfunction.

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丁香酚纳米颗粒通过抑制 PINK1/Parkin 和 BNIP3/NIX 信号通路改善多柔比星诱导的生精功能障碍

目的：阿霉素（Doxorubicin， DOX）引起睾丸组织细胞凋亡，开发药物缓解其引起的生精障碍势在必行。石竹常用于治疗男性性功能障碍。丁香酚是丁香属植物的主要成分。稳定性不足，溶解度低，限制了其药理作用。丁香酚纳米颗粒（NPs）（ENPs）有望克服这些限制。研究了ENPs对dox诱导的小鼠生殖毒性的保护作用。方法：将丁香酚包封在甲氧基聚乙二醇-聚丙交酯-共糖醇纳米颗粒（mPEG-PLGA-NPs）中，通过体内和体外实验验证其改善生精功能障碍的作用。结果：我们提出了一种将丁香酚封装到mPEG-PLGA-NPs中并形成纳米复合材料的递送系统。在体外，ENPs显著降低了多柔比星诱导的GC-1细胞中的ROS和炎症因子，调节了线粒体自噬蛋白PINK1和减数分裂相关蛋白SCP3的表达。在体内，ENPs显著提高小鼠精子活力，减少睾丸细胞凋亡和氧化应激，抑制睾丸PINK1/Parkin和BNIP3/NIX信号通路，增强减数分裂相关因子的表达。结论：鉴于其安全性和有效性，这些ENPs在减轻阿霉素诱导的生精功能障碍方面具有潜在的应用前景。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Nanomedicine NANOSCIENCE & NANOTECHNOLOGY-PHARMACOLOGY & PHARMACY

CiteScore

14.40

自引率

3.80%

发文量

511

审稿时长

1.4 months

期刊介绍： The International Journal of Nanomedicine is a globally recognized journal that focuses on the applications of nanotechnology in the biomedical field. It is a peer-reviewed and open-access publication that covers diverse aspects of this rapidly evolving research area. With its strong emphasis on the clinical potential of nanoparticles in disease diagnostics, prevention, and treatment, the journal aims to showcase cutting-edge research and development in the field. Starting from now, the International Journal of Nanomedicine will not accept meta-analyses for publication.