EFFECT OF MONOAMINE OXIDASE INHIBITOR ON FREE RADICAL OXIDATION IN RAT KIDNEYS WITH ALLOXAN-INDUCED HYPERGLYCEMIA

Abstract

Introduction. One of the most severe and dangerous complications of diabetes mellitus (DM) is diabetic nephropathy, the leading pathogenetic factor of which is considered to be prolonged hyperglycemia with the development of oxidative stress. Several leading redox-dependent mechanisms of diabetic nephropathy have been described, among which an important role is played by oxidases, as a key link in the redox balance in podocytes. The kidneys are characterized by high activity of monoamine oxidases (MAO), which are active producers of hydrogen peroxide. Meanwhile, the contribution of monoamine oxidases to the development of oxidative stress in the kidneys under conditions of prolonged hyperglycemia remains unexplored. Purpose of the study – to assess the contribution of monoamine oxidases to the development of oxidative stress in the kidneys under conditions of long-term hyperglycemia induced by alloxan. Material and methods. The study was conducted on 111 Wistar rats of both sexes, weighing 180–250 grams. Diabetes mellitus was modeled by intraperitoneal administration of alloxan monohydrate at a dose of 163 mg/kg. To assess the contribution of MAO-B to the development of oxidative stress, the selective MAO-B inhibitor selegiline was used at a dose of 5 mg/kg. Throughout the experiment, glycemia and body weight of the animals were monitored. Animals were removed from the experiment on the seventeenth day. The levels of oxidative modification of proteins, lipid peroxidation products, as well as the activity of monoamine oxidases A and B in kidney homogenates were determined by spectrophotometric methods. Results. It was found that on the fourteenth day from the moment of alloxan administration, signs of oxidative stress (increased oxidative modification of proteins) are revealed in the kidneys. The results of the correlation analysis demonstrate direct correlations in the "Alloxan" group of animals between the level of blood glucose on the 14th day of the experiment and the levels of products of oxidative modification of proteins, as well as the activity of MAO-B and the levels of products of oxidative modification of proteins and primary heptane-soluble lipid peroxidation products in kidneys. The absence of this kind of relationship in the group of animals that additionally received a MAO-B inhibitor ("Alloxan + selegiline"). Conclusions. The results of the study confirms the contribution of the intensification of free radical oxidation to the development of diabetic nephropathy during prolonged hyperglycemia, on the one hand, and the prooxidant effect of MAO-B on the other