Kuo Jui-Fang, Hsiao Yai-Ping, Wang Yao-De, Weng Hsin-Pei, Wang Chia-Chi
School of Veterinary Medicine, National Taiwan University, Taipei 106, Taiwan.
Department of Biochemistry and Molecular Medicine, UC Davis Comprehensive Cancer Center, University of California Davis, Sacramento, CA 95817, USA.
Toxics. 2025 Mar 12;13(3):204. doi: 10.3390/toxics13030204.
Fipronil (FPN), a widely used pesticide, is associated with significant immunotoxic effects, particularly impacting thymocyte survival and immune homeostasis. This study explores the mechanistic pathways underlying FPN-induced apoptosis and oxidative stress. Short-term FPN exposure (1-10 mg/kg) notably suppressed the expression of both anti-apoptotic (, , ) and pro-apoptotic (, ) genes in thymic tissues in vivo. Additionally, in isolated primary thymocytes, FPN directly decreased the expression of , , , and expression, coupled with a significant increase in pro-apoptotic expression in a dose-dependent manner. FPN treatment directly led to elevated reactive oxygen species (ROS), lipid peroxidation, mitochondrial membrane depolarization, reduced cellular metabolic activity, and depleted intracellular calcium and glutathione (GSH) levels, indicating mitochondrial dysfunction and oxidative stress. Annexin V/PI staining confirmed that FPN induced late-stage apoptosis and necrosis in primary thymocytes. These findings elucidate the immunotoxic effects of FPN on thymocytes, highlighting its detrimental impact on immune system integrity, thymic development, and T cell maturation through oxidative damage and mitochondrial-mediated apoptosis.
氟虫腈（FPN）是一种广泛使用的杀虫剂，具有显著的免疫毒性作用，尤其会影响胸腺细胞的存活和免疫稳态。本研究探讨了FPN诱导细胞凋亡和氧化应激的机制途径。短期暴露于FPN（1 - 10毫克/千克）显著抑制了体内胸腺组织中抗凋亡基因（……）和促凋亡基因（……）的表达。此外，在分离的原代胸腺细胞中，FPN直接降低了……、……、……和……的表达，并以剂量依赖的方式显著增加了促凋亡基因……的表达。FPN处理直接导致活性氧（ROS）升高、脂质过氧化、线粒体膜去极化、细胞代谢活性降低以及细胞内钙和谷胱甘肽（GSH）水平耗尽，表明线粒体功能障碍和氧化应激。膜联蛋白V/碘化丙啶染色证实FPN诱导原代胸腺细胞发生晚期凋亡和坏死。这些发现阐明了FPN对胸腺细胞的免疫毒性作用，突出了其通过氧化损伤和线粒体介导的凋亡对免疫系统完整性、胸腺发育和T细胞成熟的有害影响。
