EFFECT OF TRANSCRIPTION FACTOR KAPPA B INHIBITORS ON METABOLIC AND STRUCTURAL DISORDERS IN BONE TISSUE UNDER COMBINED EXCESSIVE INTAKE OF FLUORIDE AND SODIUM NITRATE

Abstract

This experiment carried on 40 white Wistar rats aimed at studying the effect produced by inhibitors of the nuclear transcriptional factor kappa B (NF-κB) activation on the mechanisms of metabolic and structural disorders in the femoral bones and vertebrae under combined surplus fluoride and sodium nitrate intake. It has been found out that co-administration of sodium fluoride (10 mg/kg body weight) and sodium nitrate (500 mg/kg of body weight) for 30 days disrupts the autoregulation mechanism of nitrogen monoxide (NO) level in the femoral bones of the test rats that is manifested by an increase in the activity of total NO synthase and its inducible isoform against the background of a decrease in the total arginase activity and the activity of the constitutive NO synthase isoenzymes. Under these conditions, there has been observed the growth in the concentration of free hydroxyproline, N-acetylneuraminic and hexuronic acids in the femoral bones and vertebrae that is indicative of depolymerization of collagen, sialoglycoproteins and proteoglycans, decrease in bone mass, their density, mineral saturation, strength (the Simon index elevated). Inhibitors of NF-κB activation (ammonium pyrolidine dithiocarbamate and a water-soluble form of quercetin) restore the autoregulation mechanism of the NO level in the rats’ femoral bones that is accompanied by a decrease in the total activity of NO synthase, the activity of its inducible isoform, an increase in the total arginase activity and by limited peroxinitrite formation. Ammonium pyrolidine dithiocarbamate and a water-soluble form of quercetin have been shown to result in lowering in the content of free hydroxyproline, N-acetylneuraminic and hexuronic acids in bones that confirms their effectiveness as a means for correcting depolymerization of collagen, sialoglycoproteins and proteoglycans. There has been found their property to promote the growth of bone mass and density of the femurs and vertebrae.