Background: Acute kidney injury is an urgent health problem at the junction of specialties with a high level of disability and mortality of patients. The pertinence of the study stems from conflicting data on the potential mechanisms for preventing this type of injury and the lack of a single therapeutic strategy, despite the possibility of substitution therapy. The aim of the study: To study the possibility of correcting ischemic and reperfusion renal injuries in an experiment with asialo erythropoietin and a selective inhibitor of arginase II KUD975. Materials and methods: In a series of experiments on Wistar male rats, there were studied the renoprotective properties of the prophylactic application of the combination of asialo erythropoietin (2.4 μg/kg 30 minutes before the induction of ischemia) and the selective inhibitor of arginase II KUD975 (120 mg/kg 120 minutes before the induction of ischemia) on a 40-minute bilateral model of renal ischemia-reperfusion. Renoprotective properties were evaluated by the results of biochemical markers of acute renal damage, the dynamics of glomerular filtration rate and fractionated sodium excretion, as well as the severity of microcirculatory disorders. Results: It has been established that the prophylactic use of the combination of asialo erythropoietin KUD975 leads to a decrease in the serum concentration of markers of acute renal damage, an increase in the glomerular filtration rate, a decrease in fractional sodium excretion, and a decrease in microcirculatory disorders. Conclusion: Correction of ischemic and reperfusion renal injuries in the experiment with asialo erythropoietin and selective inhibitor of arginase II KUD975 is an effective strategy for the prevention and treatment of acute kidney injury. Keywords: acute kidney injury; ischemia-reperfusion; asialo erythropoietin; inhibitor of arginase II; KUD975 Владислав Викторович Елагин, ассистент, кафедра урологии, ФГБОУ ВО «Курский государственный медицинский университет». Олег Иванович Братчиков, доктор медицинских наук, профессор, заведующий, кафедра урологии, ФГБОУ ВО «Курский государственный медицинский университет». Анастасия Александровна Ульянова, студент 4 курса по направлению подготовки 18.03.01 Химическая технология, ФГБОУ ВО «Российский химико-технологический университет имени Д.И. Менделеева».

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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Aim.The research was designed to study the renoprotective properties of erythropoietin derivatives on the kidney ischemiareperfusion experimental model.Materials and methods.The renoprotective properties of asialo erythropoietin (0.4 μg/kg and 2.4 μg/kg 30 minutes before the induction of ischemia) and carbamylated darbepoetin (50 μg/kg 24 hours before the ischemic stimulus) were studied in comparison with erythropoietin and darbepoetin in a series of experiments on male Wistar rats on a 40-minute bilateral model of renal ischemia-reperfusion. The renoprotective properties were evaluated by the results of biochemical markers of acute kidney injury, the dynamics of glomerular filtration rate and fractional sodium excretion, as well as the severity of microcirculatory disorders.Results.It was found that the prophylactic use of asialo erythropoietin (dose-dependent) and carbamylated darbepoetin leads to a decrease in the serum concentration of markers of acute renal damage, an increase in the glomerular filtration rate, a decrease in fractional sodium excretion, and a decrease in microcirculatory disorders.Conclusion.Asialo erythropoietin and carbamylated darbepoetin have the pronounced renoprotective properties and are the promising agents for the prevention and treatment of acute kidney injury.

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