里托纳维尔具有生殖毒性,取决于破坏PI3K/PDK1/AKT信号通路
Eun-Ju Jung1, Jae-Hwan Jo2, Claudine Uwamahoro1
1Department of Animal Science and Biotechnology, Kyungpook National University, Sangju 37224, Gyeongsangbuk-do, Republic of Korea.
Toxics
|January 22, 2024
概括
里托纳维尔 (RTV) 通过破坏PI3K/PDK1/AKT通路来抑制精子功能和活力. 这项研究突出了RTV的重点.
科学领域:
- 生殖生物学 生殖生物学
- 生物化学 生物化学
- 药理学 药理学是指药理学的学科.
背景情况:
- 在COVID-19治疗中使用的抗病毒药物里托纳维尔 (RTV) 也通过抑制AKT信号来表现出抗癌特性.
- 通过改变AKT活性,RTV可以引起细胞毒性并损害精子功能.
- 目前尚不清楚RTV如何影响精子中的AKT信号传输的具体机制.
研究的目的:
- 为了研究Ritonavir (RTV) 在精子中的男性生殖毒性.
- 阐明RTV对精子中酸3-酶/酸依赖蛋白酶-1/蛋白酶B (PI3K/PDK1/AKT) 信号通路的影响.
主要方法:
- 杜洛克精子被暴露在不同度的RTV.
- 诱导了精子电容.
- 评估了精子功能 (运动性,动力学,活力,电容性,体反应) 和蛋白质表达 (铁素酸化,PI3K/PDK1/AKT通路).
主要成果:
- RTV显著降低了精子运动性,运动动力学,电容性,体反应速率和细胞活力.
- RTV增加了酸铁蛋白水平和PDK1/AKT通路蛋白的表达,同时降低了PI3K水平.
- AKT表达保持不变,但PI3K表达显著下降.
结论:
- 里托纳维尔 (RTV) 可能通过PI3K/PDK1/AKT通路的改变损害精子功能,这是由增加的氨酸酸化驱动的.
- 这些发现表明RTV具有男性生殖毒性,这值得处方者和用户考虑.
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