College of Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi 030801, China.
College of Food Science and Technology, Shanxi Agricultural University, Taigu, Shanxi 030801, China.
Aquat Toxicol. 2022 Oct;251:106275. doi: 10.1016/j.aquatox.2022.106275. Epub 2022 Aug 20.
Ferroptosis plays a key role in fluorosis in aquatic organisms, but whether it is involved in fluoride-induced liver damage remains unclear. Previous studies have indicated that fluoride toxicity has the reversible tendency, but the mechanism of self-recovery after fluorosis in aquatic animals has not been elucidated. In this study, adult zebrafish and embryos were exposed to 0, 20, 40, 80 mg/L of fluoride for 30, 60 and 90 d and 3, 4 and 5 d post-fertilization (dpf), respectively. After 90 d, adult zebrafish were transferred to clean water for self-recovery of 30 d. The results showed that fluoride induced the prominent histopathologial changes in liver of adults, and the developmental delay and dark liver area in larvae. Fluoride significantly increased the iron overload, while decreased the expression levels of transferrin (tf), transferrin receptor (tfr), ferroportin (fpn), membrane iron transporter (fpn), and ferritin heavy chain (fth) in adults and larvae. Fluoride also induced the oxidative stress in adults and larvae by increasing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), while decreasing the glutathione (GSH) content and the levels of glutathione peroxidase 4 (gpx4) and solute carrier family 7 member 11 (slc7a11). Self-recovery relieved fluoride-induced ferroptosis by reducing the histopathological damage and oxidative stress, reversing the expression levels of fth and slc7a11, Fe metabolism and GSH synthesis. Lipid peroxidation and Fe metabolism may be the key factor in alleviating effects of self-recovery on fluoride toxicity. Moreover, males are more sensitive than females. Our results provide a theoretical basis for studying the alleviating effects of self-recovery on fluoride toxicity and the underlying mechanism of its protective effect.
铁死亡在水生生物氟中毒中起关键作用，但它是否参与氟诱导的肝损伤尚不清楚。先前的研究表明，氟毒性具有可逆趋势，但水生动物氟中毒后的自我恢复机制尚未阐明。在这项研究中，成年斑马鱼和胚胎分别暴露于 0、20、40、80mg/L 的氟化物中 30、60 和 90 天以及受精后 3、4 和 5 天（dpf）。90 天后，成年斑马鱼被转移到清洁水中进行 30 天的自我恢复。结果表明，氟化物诱导了成年斑马鱼肝脏的明显组织病理学变化，以及幼虫的发育迟缓和肝脏暗区。氟化物显著增加了铁过载，同时降低了成年斑马鱼和幼虫中转铁蛋白（tf）、转铁蛋白受体（tfr）、铁蛋白（fpn）、膜铁转运蛋白（fpn）和铁蛋白重链（fth）的表达水平。氟化物还通过增加活性氧（ROS）和丙二醛（MDA）的水平，同时降低谷胱甘肽（GSH）含量和谷胱甘肽过氧化物酶 4（gpx4）和溶质载体家族 7 成员 11（slc7a11）的水平，诱导了成年斑马鱼和幼虫的氧化应激。自我恢复通过减轻氟化物诱导的铁死亡引起的组织病理学损伤和氧化应激，逆转 fth 和 slc7a11 的表达水平、Fe 代谢和 GSH 合成，缓解氟化物毒性。脂质过氧化和 Fe 代谢可能是自我恢复缓解氟化物毒性的关键因素。此外，雄性比雌性更敏感。我们的研究结果为研究自我恢复对氟化物毒性的缓解作用及其保护作用的潜在机制提供了理论依据。
