Chiang Yi-Fen, Chen Yi-Tzu, Huang Ko-Chieh, Hung Wei-Lun, Chung Cheng-Pei, Shieh Tzong-Ming, Huang Yun-Ju, Ali Mohamed, Hsia Shih-Min
School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan.
School of Food Safety, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan.
Antioxidants (Basel). 2024 Nov 23;13(12):1443. doi: 10.3390/antiox13121443.
Cisplatin (CIS) is a widely used chemotherapeutic agent, but its side effects, such as oxidative stress, inflammation, and apoptosis, often lead to male reproductive damage. Oxidative stress, primarily caused by the excessive generation of reactive oxygen species (ROS), plays a critical role in disrupting testicular homeostasis, resulting in spermatogenic impairment and tissue injury. L-cysteine (CYS), a semi-essential amino acid with potent antioxidant and anti-inflammatory properties, may offer protection against CIS-induced oxidative damage. This study aimed to assess the protective potential of CYS against CIS-induced male reproductive toxicity using in vivo and in vitro models. In vitro, treatment of TM3 (Leydig) and TM4 (Sertoli) cells with CIS led to increased ROS levels, reduced cell viability, and elevated apoptosis and inflammation, all of which were significantly ameliorated by subsequent CYS exposure. In vivo, CIS-treated male rats displayed heightened oxidative stress, impaired spermatogenesis, and histopathological damage in reproductive organs. However, CYS administration for 21 days significantly reduced oxidative stress, improved sperm viability, and protected testicular tissues from damage. These findings suggest that CYS has a protective effect against CIS-induced oxidative stress and male reproductive damage, making it a promising therapeutic agent for mitigating CIS-induced reproductive toxicity.
顺铂(CIS)是一种广泛使用的化疗药物,但其副作用,如氧化应激、炎症和细胞凋亡,常常导致男性生殖损伤。氧化应激主要由活性氧(ROS)的过度产生引起,在破坏睾丸内环境稳态中起关键作用,导致生精功能受损和组织损伤。L-半胱氨酸(CYS)是一种具有强大抗氧化和抗炎特性的半必需氨基酸,可能对顺铂诱导的氧化损伤具有保护作用。本研究旨在使用体内和体外模型评估半胱氨酸对顺铂诱导的雄性生殖毒性的保护潜力。在体外,用顺铂处理TM3(睾丸间质)细胞和TM4(支持)细胞会导致ROS水平升高、细胞活力降低以及细胞凋亡和炎症增加,而随后的半胱氨酸处理可显著改善所有这些情况。在体内,经顺铂处理的雄性大鼠表现出氧化应激增强、生精功能受损以及生殖器官的组织病理学损伤。然而,连续21天给予半胱氨酸可显著降低氧化应激、提高精子活力并保护睾丸组织免受损伤。这些发现表明,半胱氨酸对顺铂诱导的氧化应激和雄性生殖损伤具有保护作用,使其成为减轻顺铂诱导的生殖毒性的有前景的治疗剂。