The experimental investigation of fibrinolytic system under the influence of flocalin in conditions of acute hypoxic kidney injury

A. I. Gozhenko, Yu. I. Gubsky, N. D. Filipets, О. О. Filipets, O. A. Gozhenko
2017 Ukrainian Biochemical Journal  
in the experiments on rats subjected to acute hypoxic histochemical nephropathy, caused by sodium nitrite and 2,4-dinitrophenol, fibrinolytic activities of blood plasma, urine, renal cortex, medulla, and papilla after treatment with flocalin -the activator of K Atp channels, were studied . It was shown that in the conditions of acute kidney hypoxic injury flocalin administration resulted in the increase and essential restoration of fibrinolysis in blood plasma diminished under hypoxia, which
more » ... due to the growth of non-enzymatic fibrinolysis, whereas in urine and renal medulla the appreciable increase of enzymatic fibrinolytic activity took place. Moreover, the treatment of hypoxic nephropathy animals by flocalin resulted in the marked restoration of kidney ion regulatory and protein excretory functions that proves the positive influence of K Atp channels activation on the one of the biochemical mechanisms of acute kidney injury as well as the protective effect of flocalin in relation to tubular cells of nephron. the obtained results testify to the beneficial effects of K Atp channels activation in the conditions of acute hypoxic kidneys injury. K e y w o r d s: flocalin, fibrinolysis, acute hypoxic kidney injury. T he essential biochemical characteristic of plasma membranes ATP-sensitive potassium (K ATP ) channels, which are gated by intracellular nucleotides ATP and ADP, is their sensitivity to disturbances in cellular metabolism. Subsequently, rapid activation and opening of K ATP channels in response to the decrease of ATP level, in particular under conditions of ischemia and hypoxia, results in plasma membrane hyperpolarization and the decrease of voltage dependent inflow of Ca 2+ ions. The latter event is accompanied by drastic disturbance of energy metabolism compliance with the functional needs of the cell and initiates the pathological cascades leading to the profound cellular pathology. The regulatory role of K ATP channels in conditions of cellular oxygenation restriction was first studied on cardiomyocytes and smooth muscle cells of blood vessels [1] , that resulted in the use of pharmacological activators of these channel types for treatment of cardiovascular diseases. In recent years the convincing evidence of cardioprotective and vasodilatory effects of the original K ATP channels fluoride-containing activator Flocalin -N-(-4difluoromethoxyphenyl)-N′-1,2,2-trimethylpropyl-N′′-cyanoguanidine [2] were obtained. Owing to the presence of fluoride, flocalin is more selective to K ATP channels and less toxic compared to other representatives of potassium channels modulators that makes it perspective and promising pharmacological substance as physiological regulator and protector of metabolic processes disturbed under hypoxic and ischemic conditions.
doi:10.15407/ubj89.04.049 fatcat:loibh2rwezabzaocteg3dbq42u