Correction of morphofunctional disorders with asialoerythropoietin and selective inhibitor of arginase II KUD975 in cases of ischemic kidney damage in the experiment

Abstract

Citation: Elagin VV, Bratchikov OI, Zatolokina MA (2018) Correction of morphofunctional disorders with asialoerythropoietin and selective inhibitor of arginase II KUD975 in cases of ischemic kidney damage in the experiment. Research Results in Pharmacology 4(4): 29-40. https://doi. AbstractIntroduction: Acute kidney injury (AKI), which is based on ischemic-reperfusion damage, is a widespread life-threatening condition and remains a serious public health problem with a high mortality rate among patients. Despite significant advances in various areas of medicine, the prevention and correction of ischemic-reperfusion kidney damage are still far from being at the desired level. Pharmacological preconditioning and the use of endothelioprotectors are promising areas in this field, therefore the purpose of this study was to analyze the nephroprotective properties of asialoerythropoietin and selective inhibitor of arginase II KUD975 in ischemic kidney damage in the experiment. Materials and methods:The study was performed on 260 white adult male Wistar rats, each weighing 180-220 g. Ischemic-reperfusion damage was simulated by applying a clamp on the renal leg for 40 minutes. To determine a degree of correction caused by morphofunctional disorders traditional functional, biochemical and morphological criteria were used. Results and discussion:When administering asialoerythropoietin and selective inhibitor of arginase II KUD975, there is observed an improvement in the glomerular filtration and microcirculation in the kidneys, decrease in the concentration of creatinine and urea, a decrease in fractional excretion of sodium and improvement in the histological pattern at different periods. The most pronounced nephroprotective effects are observed in the combined use of the test pharmacological agents, which are superior to such used in a monotherapy. The use of glibenclamide and L-NAME against the background of the correction of the pathology caused by asialoerythropoietin completely eliminates its positive effects. When glibenclamide and L-NAME are used against the background of correction of the pathology caused by the selective inhibitor of arginase II KUD975, its positive effects are completely eliminated by L-NAME. Glibenclamide does not eliminate positive effects. Conclusions:The results of the experiment prove the presence of pronounced nephroprotective properties of asialoerythropoietin and selective inhibitor of arginase II KUD975 in ischemic kidney damage in the experiment. The most pronounced effects are observed in the combined use of these pharmacological agents. The leading role in causing the positive effects from asialoerythropoietin is played by the activation of K+ATP channels and the activation of eNOS. The leading role in causing the positive effects from the selective inhibitor of arginase II KUD975 is played by the activation of eNOS.

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“…The experiments on the allergenic properties of KUD975 were carried out on bisexual sexually mature albino guinea pigs weighing 300 ± 20 g. KUD975 was administered intragastrically in the form of a suspension in 1% starch paste using a specially made atraumatic probe based on 0.1 ml of suspension per 10 g of animal body weight [21][22][23]. As a control, we used data obtained in animals with intragastric administration of an appropriate placebo volume of 1% starch paste.…”

NEPHROPROTECTIVE EFFECT OF A COMBINATION OF THE PEPTIDE MIMICKING THE a-SPATIAL STRUCTURE OF THE p ERYTHROPOIETIN CHAIN AND INFLIXIMAB IN RENAL ISCHEMIA-REPERFUSION INJURY

“…Одними из наиболее перспективных препаратов для коррекции ишемически-реперфузионной травмы почек являются эритропоэтин и его производные [1,2]. Активация гетеродимерного рецептора обуславливает развитие цитопротективных эффектов [3,4].…”