Yaroshenko T. The role of nitric oxide in the mechanisms of liver damage by xenobiotics

The object is the role of nitric oxide in the mechanisms of the liver damage caused by the allyl alcohol; the efficiency of using NO synthesis and nitric oxide donors in toxic hepatitis. The aim is to determine nitric oxide role in the pathogenesis of acute toxic hepatitis induced by the allyl alcohol as well as to investigate the possibility of correction of pathologic changes caused by the abovementioned toxin while using inhibitors of NO synthesis and nitric oxide donors. Methods – biochemical, biophysical and electrochemical methods of determining NOS activity as well as statistic ones. Novelty – for the first time it has been shown that intoxication caused by the allyl alcohol is associated with the inhibition of endothelial and activation of the inducible form of NO synthesis. It has been determined the connection between the NO product and the activation of free radical reactions, the functional state of antioxdation system and enzymes action in mitochondrial respiratory chain and the degreeof the hepatocytes necrotic changes in allyl alcohol poisoning. It has been shown that the inhibition of NO synthesis action by the nonselective NOS inhibitor L-NAME increases free radical and decreases mitochondrial oxidation in the liver damaged by the toxin and contributes to the development of the destructive processes in the hepatocytes. It has been revealed the increase in the action of calcium dependent NO synthesis while using L-arginine, it being associated with normalizing pathologic changes in hepatocytes. Complex investigation of the regulatory role of nitric oxide in pathogenesis of the liver toxic lesion caused by the allyl alcohol has been done. For the first time it has been shown that the necrotic changes in the damaged organ are connected with disbalance between the endothelial and inducible forms of NO synthesis in the liver. New approaches to the correction of the pathologic changes in the damaged by the allyl alcohol liver while using inhibitors of NO synthesis and L-arginine have been suggested.