Effect of chronic fuorosis on expression of Notch1,Hes1 in liver and its mechanism in rats

Objective To investigate the expression of Notch1, Hes1 protein in the liver with the damage induced by chronic fluorosis in rats.Methods Thirty-six healthy Sprague-Dawley(SD)rats were randomly divided into 3 groups by weight(12 in each group).The control group was given normal tap water with sodium fluoride(NaF)content of less than 1 mg/L;Low- and high-dose fluoride groups were treated with the tap water containing 5mg/L and 50 mg/L NaF.Six months after the experiment, fluoride contents in the urine and bone and serum indexes of liver function of the rats were determined;the protein expressions of Notch1, Hes1 and apoptosis factors of Bcl-2 and Bax were examined with immunohistochemistry(IHC)and protein imprinting(Western blot)analyses;the activity of superoxide dismutase(SOD), glutathione peroxidase(GSH-Px)and the content of lipid peroxide(LPO)in liver tissues of the rats were determined with xanthine oxidase method.The distribution and number of apoptosis cells in the liver tissue were detected with situ terminal transferase notation(TdT mediated dUTP Nick end labelingTUNEL).Results Compared to the control group, the fluoride contents in urine and bone were significantly higher in the rats with low- and high-dose fluoride exposure(1.89±0.12 mg/L and 2.10±0.16 mg/kg for low-dose group, 2.19±0.17 mg/L and 2.21±0.10 mg/kg for high-dose goup;all P<0.05).The protein expressions of Notch1 and Hes1 increased in the low- and high-dose fluoride groups(0.55±0.32 and 0.71±0.28 mg/kg for low-dose group, 0.74±0.92 and 0.88±0.29 mg/kg for high-dose group), with statistically significant differences(all P<0.05).Compared to the control group, LPO content was increased and SOD, GSH-Px activities were declined in the liver of the rats of fluorosis group.Compared to the control group, the expression of Bcl-2 protein in the low- and high-does fluoride group was significantly lower(0.94±0.24 and 0.71±0.22 mg/kg) and Bax protein expressions was significantly higher(1.25±0.42 and 1.43±0.46 mg/kg), with statistically significant differences(all P<0.05).TUNEL results showed that, compared to control group, the hepatocyte apoptosis increased in the rats with fluorosis.Conclusion Excessive fluoride induces oxidative stress and cell apoptosis in liver and Notch signaling pathway may be involved in the pathogenesis of liver damage caused by excessive fluoride in rats.