Kucher T. Thiol antioxidants in the pharmacological correction of the brain nitroxydergic system disturbances in conditions of chronic alcohol intoxication

The thesis for the first time presents a new scientific and practical task’s solution – the improvement of the complex pharmacotherapy of brain damage in the conditions of chronic alcohol intoxication. It was shown that the use of thiol antioxidants improves the state of the nitroxidergic system (decreases nitrotyrosine levels by 48.5%, nitrites by 50.4%, nitric oxide synthase activity by 54.8%), thiodisulfide system (reduces oxidized glutathione level by 29.1%, increases the reduced glutathione level by 102.3%, glutathione reductase and peroxidase activity by 141.1% and 63.2% respectively), increases the density of CA-1 neurons of the hippocampal region by 16.9%, decreased the density of apoptotic altered neurons by 59.7%, increases the contents of RNA in neurons by 26.4% in the rat brain. Thiocetam exceeds the effect of other thiol antioxidants (p<0.05) by the nitrotirosin level reduction, decreasing of inducible nitric oxide synthase expression, reduction of nitrogen synthase activity, the increase of the reduced glutathione level and the activity of glutathione peroxidase, the increase in the neurons of the CA-1 zone of the hippocampus density and the content of RNA in them. The neuroprotective effect of thiol antioxidants is realized by the interruption of NO-dependent mechanisms of damage of CA-1 neurons of the hippocampal zone.