Matrix metalloproteinase-9 and p53 involved in chronic fluorosis induced blood-brain barrier damage and neurocyte changes

Abstract

Introduction: A large number of basic and clinical studies have confirmed that fluoride produces toxic effects on multiple organ systems in the body including the nervous system. Material and methods: One hundred twenty Wistar rats were randomly divided into 4 groups with 30 in each group: a high fluoride group (drinking 200 mg/l fluoridated water, 24 weeks); a high fluoride control group (drinking distilled water, 24 weeks); a fluoride removal group (drinking fluoridated water, 12 W; then distilled water, 12 W) and a defluorination control group (drinking distilled water, 24 weeks). Results: The high fluoride and fluoride removal groups had spinal cord astrocyte edema. The apoptosis rate of spinal nerve cells in the high fluoride group and fluoride removal group were significantly higher (p < 0.01) than in the fluoride control and defluorination control group. The Evans blue (EB) content, matrix metalloproteinase-9 (MMP-9) and p53 expression in the high fluoride group and fluoride removal group were higher (p < 0.01) than in the fluoride control and defluorination control group. Conclusions: The apoptosis of spinal cord nerve cells is obviously higher in rats with chronic fluoride exposure. Chronic fluoride exposure leads to high expression of MMP-9, and results in increased damage of the blood-spinal cord barrier. Increased p53 may be one of the factors causing damage. Short-term removal of fluoride has no obvious recovery in apoptosis of spinal cord nerve cells; highly expressed MMP-9 and p53 may be one of the reasons for unrecovered function.