Talash V. Role of NO- and NF-кB-dependent processes in pathogenesis of modeled metabolic syndrome

The thesis is devoted to exploring the role of nitric oxide system components (different isoforms of NO-synthase and its substrate, peroxynitrite) and transcriptional nuclear factor кB in the mechanisms of derangements of oxidative processes, carbohydrate and lipid metabolism, and hemocoagulation in laboratory animals under the conditions of modelled metabolic syndrome. The results obtained have shown the functional activity of neuronal NO-synthase in the modeled metabolic syndrome limits manifestations of insulin resistance (IR), activation of lipid peroxidation (LPO) in rats, affects the indices of antioxidant (AO) blood system multidirectionally, reduces the formation of superoxide anion radical in cells of rats' aorta and the intensity of extrinsic hypercoagulation pathway. The functional activity of inducible NO-synthase in experimental conditions enhances IR, increases the signs of dyslipoproteinemia and hypertriacylglycerolemia, leads to the activation of decompensated LPO in the blood of white rats that is accompanied by the exhaustion of AO potential, decreased activity of superoxide dismutase and catalase, increased formation of superoxide anion radicals in the cells of the aorta in the rats, and promotes hypercoagulation. Introducing L-arginine to the rats under metabolic syndrome inhibits the activation of lipid peroxidation and enhances AO potential, lowers the content of low and very low density lipoproteins, limits the extent of extrinsic hypercoagulation pathway, prolongs the final stage of hemocoagulation (the formation of fibrin). It has been shown that peroxynitrite scavenger L-selenometionin and inhibitors of NF-кB (JSH-23 and metformin hydrochloride) activation under the experiment demonstrate angioprotective effect, limit the activation of lipid peroxidation, increase AO potential levels, reduce the production of superoxide anion radicals in the cells of the rats' aorta, reduce the manifestations of dyslipoproteinemia, and hypertriacylglycerolemia, and limit hypercoagulation.