| The distribution of fluorine and fluoride in nature is very wide and they are used widely in chemistry, medicine, agriculture and et al. Fluorine is one of the necessary trace elements for the body and it has many physiological effects. But if it is ingested excessively over a prolonged period, it can accumulate in the body and adversely influence many tissues and organs characterized by a vast array of symptoms and pathological changes in addition to the well-known effects on skeleton and teeth. Endemic fluorosis is a serious disease that threatened the health of people in our country. It distributes widely and there are a lot of people threatened by it. But the mechanism is still unclear. The situation of fluorosis is very serious in China and further study on its toxicity is a pressing task.Liver is an important metabolism and detoxication organ for the body. Excessive fluoride ingestion inevitably induces toxicity to the liver. Epidemiological and animal studies indicate that fluorosis induced the histology and function of liver abnormal. This study combines the studies done before and the theory on free radical to explore the role of oxidative stress in the hepatotoxicity induced by fluoride.Objectives1. To study the role of oxidative stress in the hepatotoxicity induced by sub-chronic fluorosis. Analyses the changes of the indices of the liver function, lipid peroxidation, the structure damages and the correlation among them.2. Primary cultured rat hepatocytes were cultured with various concentrations of sodium fluoride for 24 hours to study the toxicity and possible mechanism induced by fluoride from morphological, enzymological and biochemical changes.Methods1. Animal experimentsWistar rats were randomly divided into four groups. The rats were given various concentration of sodium fluoride in drinking water for three months. The content of fluoride in urine and serum were assayed. The contents of malondial-dehyde and GSH and the activities of superoxide (SOD) , GSH-Px, serum glu-tamate pyruvate transaminase (SGPT) and serum glutamate oxalate transaminase (SGOT) were also assayed. Meanwhile observed the morphological and ultra-structure changes.2. Cell cultureThe primary cultured rat hepatocytes were cultured with various concentration of sodium fluoride for 24 hours to observe its effects on the cell viability (examined by MTT assay) , morphological changes, activity of AST, ALT and contents of MDA in the medium. Using these indices to explore the toxicity of sodium fluoride and its possible mechanism.ResultsAnimal experiments1. After three months with the various indicated concentrations of fluoride in their drinking water, the rats had fluoride levels in their urine and serum that were significantly higher than those of the control group and dental fluorosis were observed in the rats of the experimental groups. All manifestations indicated that fluorosis rats model were produced successfully.2. The activities of SGPT and SGOT were elevated in dose-dependent manner following NaF treatment. The activity of SGPT in 150 mg/L group was significantly higher than the control group ( p <0. 01). The activities of SGOT in 100 mg/L and 150 mg/L group were significantly higher than the control group3. The content of MDA in 150 mg/L group increased significantly compared with the control group. There was a positive correlation between MDA and the fluoride content in serum (r =0.559 ,p <0.01) . The activities of SOD and GSH-Px decreased with the increased concentration of fluoride. The activities of SOD in 100 mg/L and 150 mg/L decreased significantly compared with the control group (p<0.05) . There was a negative correlation between SOD, GSH-Px and the fluoride content in serum ( r = - 0.563, p<0.01; r =- 0.419, p< 0.05). The contents of GSH in the experimental groups were significantly decreased compared with the control group. There was a negative correlation between GSH and dose and blood fluoride ( r = -0.848, p<0.01; r = - 0.799, p<0.01).4.
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