ROLE OF NF-κB ACTIVATION IN CHANGES OF NITRIC OXIDE PRODUCTION IN SKELETAL MUSCLES DURING METABOLIC SYNDROME

Abstract

Nitric oxide, as a signaling molecule, plays an ambiguous role in many pathological processes. On the one hand, nitric oxide is necessary for maintaining the tone of the vascular wall of arteries and prevents the development of ischemia in various organs and skeletal muscles in particular. On the other hand, excessive production of nitric oxide in the tissue can contribute to the formation of toxic metabolites, such as peroxynitrite that leads to the development of nitrosative damage to various organs and tissues. Metabolic syndrome is also one of the diseases accompanied by disturbances in the nitric oxide production system. Currently, the sources of nitric oxide production, the predominant ways of its metabolism, and the influence of the transcription factor NF-κB on these processes in skeletal muscles under the conditions of the metabolic syndrome are insufficiently studied. The purpose of this study is to study the effect of an inhibitor of the activation of the transcription factor NF-κB on the production of nitric oxide and the concentration of its metabolites in the biceps femoris muscle of rats under the conditions of modeling the metabolic syndrome. The experimental study was carried out on male Wistar rats weighing 200-260 g. The animals were randomly divided into 4 groups of 6 animals each. Animals of group 1 (control group) received a standard vivarium diet. In group 2 (metabolic syndrome), in addition to the standard diet, the animals received a 20% fructose solution as their sole source of drinking water for 60 days. In group 3, the animals were given a standard vivarium diet and were injected intraperitoneally with ammonium pyrrolidine dithiocarbamate at a dose of 76 mg/kg, three times a week for 60 days. Group 4 received the same diet as group 2 along with the injections administered in group 3. In 10% homogenate of the biceps femoris muscle, the following were determined: total NO-synthase activity, activity of constitutive and inducible isoforms of NO-synthase, arginase activity, aitrate- and nitrite reductase activity, concentrations of nitrite, peroxynitrite, nitrosothiols, and sulfides. The administration of ammonium pyrrolidinedithiocarbamate during metabolic syndrome simulation resulted in a reduction in total NO-synthase activity and inducible NO-synthase activity by 33.85% and 34.66%, respectively, compared to the metabolic syndrome group; arginase activity decreased by 37.56%, while nitrate and nitrite reductase activities were reduced by 19.29% and 47.71%, respectively; nitrite concentration increased by 21.77%, peroxynitrite concentration decreased by 32.05%, nitrosothiol concentration increased by 29.27%, and sulfide concentration decreased by 17.39% compared to the group with metabolic syndrome. Activation of the transcription factor NF-κB under metabolic syndrome conditions leads to increased nitric oxide production through both L-arginine-dependent and L-arginine-independent pathways in the biceps femoris muscle, enhances arginase activity, and results in elevated peroxynitrite formation.