Metabolism of nitric oxide under the conditions chronic alcohol intoxication modelling

Abstract

It was experimentally shown that ethanol affects the production of nitric oxide in rats. However, nitric oxide can have both a protective effect by weakening the harmful effect of ethanol on the microcirculation of the liver, and lead to liver damage by active forms of nitrogen. The purpose of the study is to study changes in the nitric oxide cycle under the conditions of modeling chronic alcohol intoxication in rats. Experiments were performed on 30 white, mature male Wistar rats, weighing 180–220 g. The animals were divided into 2 groups: I – control (n=6); II group – animals with alcoholic hepatitis (n=24) modelled by the method of forced intermittent alcoholization for 5 days, with a repeat after two days by intraperitoneal injection of a 16.5% ethanol solution in a 5% glucose solution, at the rate of 4 ml/kg of body weight. Animals were removed from the experiment on days 10, 14, 21 and 28 by taking blood from the right ventricle of the heart under thiopental anesthesia. The activity of inducible and constitutive isoforms of NO-synthase, concentration of nitrite, nitrosothiols and peroxynitrites of alkali and alkaline earth metals, the activity of nitrite reductase, nitrate reductase and arginase were determined in rat liver homogenate. Chronic alcohol intoxication modelling for 10–28 days leads to a violation of the formation and metabolism of nitric oxide with the predominant formation of its toxic metabolites, such as peroxynitrites and nitrites, which threatens the development of nitrosative stress in the liver. Chronic alcohol intoxication on the 10th–28th days of the experiment is accompanied by a sharp decrease in the activity of the arginase-dependent pathway of arginine metabolism in the liver of rats, which indicates a violation of the deamination processes in the Krebs-Handzeleit cycle.

Keywords: nitrites, NO-synthase, peroxynitrite, alcohol, liver, rats.