Henan Key Laboratory of Environmental and Animal Product Safety, College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, Henan 471000, China; Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi, China.
Ecotoxicol Environ Saf. 2024 Feb;271:115947. doi: 10.1016/j.ecoenv.2024.115947. Epub 2024 Jan 11.
Fluoride induced reprotoxicity through oxidative stress-mediated reproductive cell death. Hence, the current study evaluated the importance of the MST/Nrf2/MAPK/NQO-HO1 signaling pathway in fluorosis-induced reproductive toxicity. For this purpose, the reproductive toxicity of sodium fluoride (NaF) at physiological, biochemical, and intracellular levels was evaluated. In-vivo, NaF at 100 mg/L instigated physiological dysfunction, morphological, stereological, and structural injuries in the gut-gonadal axis of fluorosis mice through weakening the antioxidant signaling, Nrf2/HO-1/NQO1signaling pathway, causing the gut-gonadal barrier disintegrated via oxidative stress-induced inflammation, mitochondrial damage, apoptosis, and autophagy. Similar trends were also observed in-vitro in the isolated Leydig cells (LCs) challenging with 20 mg/L NaF. Henceforth, activating the cellular antioxidant signaling pathway, Nrf2/HO-1/NQO1, inactivating autophagy and apoptosis, or attenuating lipopolysaccharide (LPS) can be the theoretical basis and valuable therapeutic targets for coping with NaF-induced reproductive toxicity.
氟化物通过氧化应激介导的生殖细胞死亡引起生殖毒性。因此，本研究评估了 MST/Nrf2/MAPK/NQO-HO1 信号通路在氟中毒诱导的生殖毒性中的重要性。为此，评估了生理、生化和细胞内水平的氟化钠 (NaF) 的生殖毒性。在体内，100mg/L 的 NaF 通过削弱抗氧化信号、Nrf2/HO-1/NQO1 信号通路，在氟中毒小鼠的肠-性腺轴引发生理功能障碍、形态学、体视学和结构损伤，导致肠-性腺屏障通过氧化应激诱导的炎症、线粒体损伤、细胞凋亡和自噬而瓦解。在体外分离的睾丸间质细胞 (LCs) 中用 20mg/L NaF 处理时也观察到类似的趋势。因此，激活细胞抗氧化信号通路 Nrf2/HO-1/NQO1，抑制自噬和细胞凋亡，或减轻脂多糖 (LPS)，可以为应对 NaF 诱导的生殖毒性提供理论基础和有价值的治疗靶点。
