Research Results in Pharmacology (Jun 2023)
Correction of renal ischemia/reperfusion injury with the combination of Infliximab and the erythropoietin-derived peptide mimetic pHBSP
Abstract
Introduction: Due to the high social and economic value of acute kidney injury, the scientific community is focused on methods of diagnosis and treatment of this pathology. A number of studies have already revealed cytoprotective effects of the helix B–derived erythropoietin peptide and infliximab in simulated ischemia/reperfusion injury of liver, myocardium, and nervous tissue. The aim of this research was to study the renoprotective effects of the combination of pHBSP and infliximab on the renal ischemia/reperfusion injury. Materials and Methods: The experiment was performed in 230 white male Wistar rats. The animals were treated with pHBSP and infliximab. Under anesthesia, a unilateral right nephrectomy was performed and the contralateral renal pedicle was clamped. Functional tests were performed and tissue samples were taken for laboratory studies 5 minutes, 24 hours and 72 hours after reperfusion. Results and Discussion: The results obtained confirm the dose-dependent renoprotective activity of the helix B–derived erythropoietin peptide and infliximab. The nephroprotective activity of the combination of pHBSP at a dose of 25 mcg/kg and infliximab at a dose of 10 mg/kg significantly exceeded the effect of a single-drug therapy. This is evidenced by the normalization of renal tubule function, a significant increase in the microcirculation level, the absence of rough lesion during pathomorphological examination, as well as a decrease in the expression of TNF-α by 54% and IL-1β by 65% in comparison with the ischemia/reperfusion group according to immunohistochemistry examination. The important role of ATP-sensitive potassium channel in the renoprotective activity of pHBSP has been confirmed. Conclusion: The renoprotective activity of the helix B–derived erythropoietin peptide and infliximab has been confirmed, and the advantage of their combined administration for the correction of morphofunctional disorders in simulated renal ischemia/reperfusion injury due to the multimodal effect on pathogenetic processes has been established.
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