Dissertation is devoted to studying the mechanisms of action of vitamin B3 and its derivatives in conditions of experimental type 1 diabetes mellitus. It has been established that NAm and N-GABA inhibiting the activation of the polyol pathway of exchange of glucose in the brain, its structures and in the sciatic nerve, prevent structural changes in these organs, restoring their functions. It was revealed that the development of neurodegenerative changes in the brain is accompanied by a structural transformation of cytoskeleton proteins, blood vessel dysfunctions, the development of apoptosis and reactive gliosis, a violation of the structural integrity of brain cells, and a violation of the permeability of the blood-brain barrier. For the first time, it has been shown that in the brain of diabetic animals there are significant changes in the expression of key proteins, which is confirmed by the decrease in the content of nNOS, VEGF, MBP, NFL, NFN, while the content of NF-κB, BAX, GFAP, NFM increased, however the content of vimentin did not change. It was first established that the mechanisms of action of NAm and N-GABA are realized both through NAD-dependent processes and indirectly by involving other processes at the level of protein content, since NAm and N-GABA exhibited a correction effect on nNOS, VEGF, NF-κB, BAX, with NAm having a more normalizing effect on the content of NFL, NFN, and N-GABA on the content of MBP. We also first found that the administration of N-GABA resulted in an increase in the content of vimentin and GFAP, which may be the result of the proliferation of astrocytes as an adaptation-protective reaction. It was discovered for the first time that NAm and N-GABA prevented the violation of the structural integrity of the brain cells and impaired permeability of the blood-brain barrier, which was evidence of a decrease of GFAP and NFL in the serum of diabetic animals.
It has been established that the mediated NAm and N-GABA regulation of NAD-dependent processes with type 1 diabetes and its complications are carried out against the background of the existing functional relationship between hyperglycemia, activation of oxidative stress, development of reactive gliosis and vascular dysfunctions, apoptosis, demyelination of neurons in the development of diabetic neuropathy. Thus, the compounds studied can be promising as corrective compounds for the treatment of diabetes mellitus and its complications.
