Frenkel Y. NO-dependent mechanisms of oxidative metabolism disorders in rats' brain under impaired melatonin production

This dissertation is aimed to determine the role of the components of nitric oxide (NO-synthase and its substrate, peroxynitrite) in the pathogenesis of oxidative metabolism disturbances in brain tissue under modeled disorders of melatonin production. It has been demonstrated the simulation of hypomelatoninemia in the cerebral hemispheres results in the progressive increase in the activity of NO-synthase (NOS, due to inducible one), production of superoxide anion radical NADH- and NADPH-oxidase complexes, activation of decompensated peroxidation lipids, progressive decrease in the activity of antioxidant enzymes (superoxide dismutase and catalase), and inhibition of bioenergetic processes. There have been found out some differences in the sensitivity of the antioxidant system of the brain hemispheres to hypo- and hypermelatoninemia. The research has also shown the differences in the effect provided by different isoforms of NO (neuronal and inducible) upon the level of superoxide anion-radical production, activation of lipid peroxidation, antioxidant protection and bioenergy processes in the cerebral hemispheres of the rats under chronic experimental hypomelatoninemia. It has been proven the administration of L-arginine in chronic experimental hypomelatoninemia limits the activation of lipid peroxidation, increases energy potential in the brain tissue. The research has revealed that under chronic hypomelatoninemia the NF-кB activation and peroxynitrite formation significantly affect oxidative metabolism in brain tissue. Administration of nuclear translocation inhibitor NF-кB JSH-23 (4-methyl-N-(3-phenylpropyl) benzene-1.2-diamine) and L-selenomethionine peroxynitrite scavenger limits the production of superoxide anion-radicals and the level of lipid peroxidation, increases antioxidant protection and energy potential in the cerebral hemispheres.