Changes Of Chronic Fluorosis On Expression Of Nrf2/ARE Signal Pathway In Rat Brains

Objective In order to investigate the changes of expression ofNrf2/ARE signal pathway at proteins and mRNA level in rat brains with the chronicfluorosis,and reveal the mechanism of brain damage. Methods Ninety SD rats weredivided randomly to three groups of30each (a half females and a half males), e.g. thecontrol group fed with normal tap-water (<0.6mg/L NaF), high-fluoride group with50mg/L fluoride added in drinking water; and the high-fluoride plus Vitamin E (VitE)group with the same dose of NaF as the high-fluoride group, but giving5mg/kg VitEby intragastric administration. The experiment period was10months. The fluoridecontents in urine and bone were detected by Fluoride-ion selective electrode. Testingthe rats learning and memory function by Morris water maze experiment.Theexpression of NF-E2-related factor2(Nrf2), Kelch-like ECH-associated protein-1(Keap1), NAD(P)H quinone oxidoreductase-1(NQO1), Heme Oxygenase-1(HO1) atboth the protein and mRNA levels were detected by Western blotting,immunohistochemistry, and real-time PCR, respectively. The histological structurewas observed under light microscopes. The activity of SOD and the content of lipidperoxidation (MDA) were measured by biochemistry methods. Results The dentalfluorosis, high contents of fluoride in urine and born were observed in the rats of thehigh-fluoride group. The nissl body is decreased in neurons. As compared withcontrols, the protein expressions of Nrf2，Keap1，NQO1and HO1in rat brains withfluorosis were increased(P<0.05). In the cortices and hippocampi of the brains of ratswith fluorosis, the level of those four protein were clearly elevated. The alternationsof expression of the protein levels were almost the same as the corresponding changes at the mRNAs encoding(P<0.05). Interestingly, VitE can attenuate toxicities inducedby chronic fluorosis, including the high levels of Nrf2, Keap1, NQO1and HO1expressions and oxidative stress resulted from fluoride. Correlative analysis showedthat increased levels of Nrf2, Keap1, NQO1and HO1in the brain were positivelycorrelated with the fluoride content in bone and the level of MDA in the brain, butnagatively with the activity of SOD. Conclusion These findings indicate thatchronic fluorosis induces changes of Nrf2/ARE signal pathway. The rats of rats of thefluorosis progressive damage on learning and memory function. The expression ofNrf2，Keap1，NQO1and HO1in brain of the rats with fluorosis was significantlyincreased with a correlation to the level of oxidative stress, whereas vitamin E canattenuate these abnormal changes resulted from fluoride, which might be connected tothe mechanism of brain damages induced by the disease.