Effect of Ap-1 Transcription Factor Inhibitor on Structural, Metabolic and Biomechanical Changes in Bone Tissue During Combined Excessive Intake of Sodium Fluoride and Sodium Nitrate

Abstract

This article highlights the effect produced by the inhibitor of the AP-1 transcription factor activation on the mechanisms of structural, metabolic and biomechanical disorders in the femoral bones and vertebrae during combined excessive intake of sodium fluoride and sodium nitrate. The experiment was conducted on 30 white rats divided into 4 groups: the 1st included the intact animals, the 2nd group involved the rats subjected to the co- administration of sodium fluoride (10 mg / kg body weight) and sodium nitrate (500 mg / kg body weight) for 30 days, the 3rd group included the animals, which starting from the 15th day of intoxication, were injected SR 11302 ((E, E, Z, E) -3-Methyl-7- (4-methylphenyl) - 9- (2,6,6-trimethyl-1-cyclohexen-1-yl) -2,4,6,8-nonatetraenoic acid), an inhibitor of AP-1 activation in a dose of 1 mg / kg intraperitoneally 3 times a week. It has been revealed that the SR 11302 administration restores the mechanism of NO autoregulation in the femoral bones during the sodium fluoride and sodium nitrate co- administration, reducing the total activity of NO synthase and activity of its inducible isoform under a reciprocal increase in total arginase activity, and suppresses the peroxynitrite production. This is accompanied by a decrease in the activity of enzymes, which are known as markers of bone resorption (acid phosphatase and its bone isoform) and restriction of the depolymerization of collagen, proteoglycans and sialoglycoproteins of the connective (bone) tissue in the femurs and vertebrae. Moreover, the introduction of SR 11302 under the experimental conditions is accompanied by an increase in the density and mineral saturation of the femurs and vertebrae, and an improvement in the biomechanical characteristics of the femurs (their strength and elasticity).