Mechanisms of Nitrosative Stress and Destruction of the Organic Matrix of the Rat Mandible in the Recovery Period After Its Incomplete Fracture Under Conditions of Chronic Alcohol Intoxication

Abstract

The mechanisms of nitrosative stress and depolymerization of biopolymers of the mandibular bone tissue after its incomplete fracture under conditions of chronic alcohol intoxication were investigated. The experiments were conducted on 20 white Wistar rats weighing 190-240 g, divided into 4 groups: Group 1 - intact animals, Group 2 - after reproduction of chronic alcohol intoxication, Group 3 - after modeling of mandibular fracture, Group 4 - after reproduction of mandibular fracture in the setting of chronic alcohol intoxication. The activity of total NO synthase, its constitutive and inducible isoforms, ornithine decarboxylase, concentrations of peroxynitrites of alkaline and alkaline-earth metals, free hydroxyproline, N-acetylneuraminic and hexuronic acids were determined in the homogenate of the standard mandible area by spectrophotometric method. It has been shown that the reproduction of chronic alcohol intoxication significantly increases the total and inducible NO synthase activity in the mandibular homogenate, accompanied by an increase in the concentration of the key marker of nitrosative stress – peroxynitrite. On the 14th day after the reconstruction of a mandibular fracture on the background of chronic alcohol intoxication, NO synthase activity and the content of peroxynitrites of alkaline and alkaline-earth metals in the bone homogenate exceed the results of groups with separate action of pathogenic factors. Under these conditions, the activity of the key enzyme of polyamine biosynthesis, ornithine decarboxylase, significantly decreases, and the depolymerization of bone biopolymers (collagen, glycoproteins, and proteoglycans) increases, which creates prerequisites for disruption of reparative processes in the fracture site.