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

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.