Nuclear factor E2 related factor 2 may alleviate liver injury by regulating iron overload and lipid peroxidation induced by chronic fluorosis

IF 3.6 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Trace Elements in Medicine and Biology Pub Date : 2025-10-08 DOI:10.1016/j.jtemb.2025.127775

Xiao Xiao , Xi Tu , Na Wei , Wen-Wen He , Xiao-Xiao Zeng , Wei Liao , Jie Deng , Yang-Ting Dong , Xiao-Lan Qi , Yan Xiao , Wei Hong , Yan He , Di-Dong Lou , Zhi-Zhong Guan

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引用次数: 0

Abstract

Background

The aim of the study is to explore the regulatory effect of nuclear factor erythroid 2-related factor 2 (Nrf2) on iron overload and lipid peroxidation in pathogenesis of liver injury induced by fluorosis. METHODS Liver function of the individuals residing in endemic fluorosis area and the rats were examined by biochemical analysis. The histopathological changes of rat liver were observed under light and electron microscopes. The parameters relating iron overload and lipid peroxidation were determined by biochemical and molecular biological methods. HepG2-cells were treated with overexpressed plasmid or siRNA of Nrf2. RESULTS The results showed that the disfunction of liver was related to the severity of dental fluorosis in population of fluorosis area and the changed liver function and histopathology were observed in rats with chronic fluorosis. Fluoride exposure induced iron overload, exhibiting the high levels of Nrf2, total iron and ferrous ion, the changed protein and mRNA levels of FTL, FPN1, hepcidin and S100A9; and the stimulated lipid peroxidation, including the increased MDA and ROS, and the decreased GSH, GPX4 and SLC7A11 in rat liver and HepG2-cells. Interestingly, overexpression of Nrf2 attenuated the changes of iron overload and peroxidative injury of cultural cells exposed to fluoride, and while silencing Nrf2 enhanced these hepatic damages by fluoride. CONCLUSION Our results indicated that fluoride exposure caused iron overload and lipid oxidative injury in liver, which was involved in the impairment of liver function. Nrf2 may play a protective role in alleviating the liver injury by regulating iron overload and lipid peroxidation induced by chronic fluorosis.

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核因子E2相关因子2可能通过调节慢性氟中毒所致的铁超载和脂质过氧化而减轻肝损伤

本研究旨在探讨核因子红细胞2相关因子2 （Nrf2）在氟中毒肝损伤发病机制中对铁超载和脂质过氧化的调控作用。方法对地氟病地区个体及大鼠肝功能进行生化检测。光镜和电镜下观察大鼠肝脏组织病理变化。采用生物化学和分子生物学方法测定了铁超载和脂质过氧化的相关参数。用过表达的Nrf2质粒或siRNA处理hepg2细胞。结果氟中毒地区人群的肝功能障碍与氟牙症的严重程度有关，并观察慢性氟牙症大鼠肝功能和组织病理学的变化。氟暴露诱导铁超载，表现为Nrf2、总铁离子和亚铁离子水平升高，FTL、FPN1、hepcidin和S100A9蛋白和mRNA水平改变；大鼠肝脏和hepg2细胞中MDA和ROS升高，GSH、GPX4和SLC7A11降低。有趣的是，Nrf2的过表达减弱了氟暴露培养细胞铁过载和过氧化损伤的变化，而Nrf2的沉默则增强了氟对肝脏的损害。结论氟暴露引起肝脏铁超载和脂质氧化损伤，参与了肝功能损害。Nrf2可能通过调节慢性氟中毒引起的铁超载和脂质过氧化，起到减轻肝损伤的保护作用。

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来源期刊

Journal of Trace Elements in Medicine and Biology 医学-内分泌学与代谢

CiteScore

6.60

自引率

2.90%

发文量

202

审稿时长

85 days

期刊介绍： The journal provides the reader with a thorough description of theoretical and applied aspects of trace elements in medicine and biology and is devoted to the advancement of scientific knowledge about trace elements and trace element species. Trace elements play essential roles in the maintenance of physiological processes. During the last decades there has been a great deal of scientific investigation about the function and binding of trace elements. The Journal of Trace Elements in Medicine and Biology focuses on the description and dissemination of scientific results concerning the role of trace elements with respect to their mode of action in health and disease and nutritional importance. Progress in the knowledge of the biological role of trace elements depends, however, on advances in trace elements chemistry. Thus the Journal of Trace Elements in Medicine and Biology will include only those papers that base their results on proven analytical methods. Also, we only publish those articles in which the quality assurance regarding the execution of experiments and achievement of results is guaranteed.