Changes of P-glycoprotein and nuclear factor κB in the cerebral cortex of rat with chronic fluorosis

Abstract

Objective The aim of the study was to investigate the expression of P-glycoprotein (P-gp)and nuclear factor κB (NF-κB) in the cerebral cortex of rat with chronic fluorosis,and to reveal the mechanisms of damaged nervous system resulted from the toxicity of fluoride.Methods Sixty SD rats were randomly divided into three groups.The rats in each group were given drinking water containing different levels of fluoride:control group less than 0.5 mg/L,small amount of fluoride exposure group 10.0 mg/L and large amount of fluoride exposure group 50.0 mg/L.The animals were examined at the sixth month after initiating the experiment.Protein levels of P-gp and NF-κB in brain tissues were detected by immunocytochemistry and Western blotting,and the P-gp protein and mRNA level by quantitative real time PCR method.Results As compared to the control group(28.21 ±6.13),the numbers of positive staining cells by P-gp antibody in the cortex of rat brains were significantly increased in both the small and the large amount of fluoride exposure groups[(48.46 ± 8.00),(53.72 ± 9.15),respectively,all P ＜ 0.05] ; the protein levels in the control group(100.00 ± 3.86)％ detected by Western blotting were significantly increased in the cortex of rat brains treated with fluoride in both the small and the large amount of fluoride exposure groups[(189.47 ± 3.14)％,(191.36 ± 11.09)％,respectively,all P ＜ 0.05].The significantly increased expression of NF-κB at the protein level was observed in the cortex of rat brains of the small and the large amount of fluoride exposure groups[(365.97 ± 6.04)％ and (417.15 ± 10.89)％,respectively] as compared with the control group[(100.00 ± 10.07)％,all P ＜ 0.05].The mRMA level of P-gp in the cortex of rat brains of the small and the large amount of fluoride exposure groups(2396 ± 427,3479 ± 371,respectively) were higher than that of the control group(260 ± 106,all P ＜ 0.05).Conclusion The increased expressions of P-gp and NF-κB in the cortex of rat brains are induced by chronic fluorosis,which might be connected with the mechanism of brain damages. Key words: Fluoride poisoning; Rats; P-glycoprotein; Nuclear factor κB