Oleshchuk O. Role of nitric oxide in the pathogenesis of different genesis liver injuries

The manuscript is devoted to investigation of L-arginine-nitric oxide role in the pathogenesis of toxic, cholestatic, cirrhotic and ischemic-reperfusion injuries of liver by modulating the NO synthesis was studied. It was found that nitric oxide precursor L-arginine and L-arginine L-glutamate, regardless of the type of injury, causes hepatoprotective effect, resulting in inhibition of cytolysis and cholestasis processes, improving mitochondrial respiration and detoxification in liver, reduction of metabolic acidosis, imbalance in pro-oxidant-antioxidant system, decline of iNOS and increase of eNOS expression, reducing pro-inflammatory cytokines that leads to restoration of the morphological structure of the liver. Nonselective NO-synthase blocker N-nitro-L-arginine, despite the type of pathological process, causes a further injury of the liver structure, growth cytolysis and cholestasis phenomena, depletion of antioxidant defense system components, activation of lipid peroxidation processes, dysfunction of the electron transport system of mitochondria and processes detoxification in the liver; the growth effects of metabolic acidosis and endotoxemia against low levels of nitrite and nitrate anions, eNOS, iNOS content and increased concentration of pro-inflammatory cytokines. Usage of selective iNOS inhibitors aminoguanidine and melatonin in hepatitis, cirrhosis and cholestasis leads to partial improvement of functional status and metabolism in the liver. It was established that aminoguanidine has a negative impact on the state of the liver in ischemia-reperfusion, indicating the protective effect of iNOS-induced nitric oxide synthesis in the early periods of reperfusion.