Correction of renal ischemia/reperfusion injury with the combination of Infliximab and the erythropoietin-derived peptide mimetic pHBSP

Authors

  • Aleksandr S. Netrebenko Belgorod State National Research University

DOI:

https://doi.org/10.18413/rrpharmacology.9.10032

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.

Graphical Abstract

mceclip1-9f04929c47b1dd28b6907c1eba384dc7.png

Keywords:

pHBSP, infliximab, ischemia/reperfusion, TNF-α, preconditioning, inflammation

References

Bakker ALM, Mathijssen H, Azzahhafi J, Swaans MJ, Veltkamp M, Keijsers RGM, Akdim F, Post MC, Grutters JC (2021) Effectiveness and safety of infliximab in cardiac Sarcoidosis. International Journal of Cardiology 330: 179–185. https://doi.org/10.1016/j.ijcard.2021.02.022 [PubMed]

Basile DP, Yoder MC (2014) Renal endothelial dysfunction in acute kidney ischemia reperfusion injury. Cardiovascular &Hematological Disorders-Drug Targets 14(1): 3–14. https://doi.org/10.2174/1871529x1401140724093505 [PubMed] [PMC]

Bethesda MD (2017) LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. National Institute of Diabetes and Digestive and Kidney Diseases. [PubMed]

Bi XG, Li ML, Xu W, You JY, Xie D, Yuan XF, Xiang Y (2020) Helix B surface peptide protects against acute lung injury through reducing oxidative stress and endoplasmic reticulum stress via activation of Nrf2/HO-1 signaling pathway. European Review for Medical and Pharmacological Sciences 24(12): 6919–6930. https://doi.org/10.26355/eurrev_202006_21683 [PubMed]

Bratchikov OI, Pokrovskiy MV, Elagin VV, Kostina DA (2018) The correction of endothelial dysfunction with the help of distant ischemic and pharmacological preconditioning with thermal local asphyxia of kidney. Urology Herald 6(2): 4–12. https://doi.org/10.21886/2308-6424-2018-6-2-4-12

Elagin VV, Bratchikov OI (2018) Сorrection of microcirculatory damages in ischemic and reperfusive kidney injury in experiment. SmolenskyMedical Almanac [SmolenskiyMeditsinskiyAlmanakh] 4: 95–97. [in Russian]

Elagin VV, Bratchikov OI, UlyanovaАА (2018) Approaches to correction of ischemic and reperfusion kidney injuries in experiment. Research Results in Biomedicine 4(3): 63–69. https://doi.org/10.18413/2313-8955-2018-4-3-0-6

Forbes CM, Rendon RA, Finelli A, Kapoor A, Moore RB, Breau RH, Lacombe L, Kawakami J, Drachenberg DE, Pautler SE, Jewett MMA, Saarela O, Liu Z, Tanguay S, Black PC (2016) Disease progression and kidney function after partial vs. radical nephrectomy for T1 renal cancer. Urologic Oncology 34(11): 486–486. https://doi.org/10.1016/j.urolonc.2016.05.034 [PubMed]

Gobe GC, Coombes JS, Fassett RG, Endre ZH (2015) Biomarkers of drug-induced acute kidney injury in the adult. Expert Opinion on Drug Metabolism &Toxicology 11(11): 1683–1694. https://doi.org/10.1517/17425255.2015.1083011[PubMed]

Golmohammadi MG, Banaei S, Nejati K, Chinifroush-Asl MM (2020) Vitamin D3 and erythropoietin protect against renal ischemia-reperfusion injury via heat shock protein 70 and microRNA-21 expression. Scientific Reports 10(1): 20906. https://doi.org/10.1038/s41598-020-78045-3 [PubMed] [PMC]

Grebien F, Kerenyi MA, Kovacic B, Kolbe T, Becker V, Dolznig H, Pfeffer K, Klingmüller U, Müller M, Beug H, Müllner EW, Moriggl R (2008) Stat5 activation enables erythropoiesis in the absence of EpoR and Jak2. Blood 111(9): 4511–4522. https://doi.org/10.1182/blood-2007-07-102848 [PubMed] [PMC]

Jiang YL, Peng CX, Wang HZ, Qian LJ (2019) Comparison of the long-term follow-up and perioperative outcomes of partial nephrectomy and radical nephrectomy for 4 cm to 7 cm renal cell carcinoma: a systematic review and meta-analysis. BMC Urology 19(1): 48. https://doi.org/10.1186/s12894-019-0480-6 [PubMed] [PMC]

Khvan MA (2013) Mediators of inflammation in acute kidney injury.Nephrology and Dialysis 15(2): 106–115.

Kostina DA, Pokrovskaya TG, Poltev VY (2021) Renoprotective effect of carbamylated darbepoetin and udenafil in ischemia-reperfusion of rat kidney due to the effect of preconditioning and inhibition of nuclear factor kappa B. Research Results in Pharmacology 7(1): 1–19. https://doi.org/10.3897/rrpharmacology.7.63059

Li X, Tang Y, Ding Y, Chen Y, Hou M, Sun L, Qian G, Qin L, Lv H (2021) Higher efficacy of infliximab than immunoglobulin on Kawasaki disease, a meta-analysis. European Journal of Pharmacology 899: 173985. https://doi.org/10.1016/j.ejphar.2021.173985 [PubMed]

Lou J, Zhang H, Qi J, Xu Y, Wang X, Jiang J, Hu X, Ni L, Cai Y, Wang X, Gao W, Xiao J, Zhou K (2022) Cyclic helix B peptide promotes random-pattern skin flap survival via TFE3-mediated enhancement of autophagy and reduction of ROS levels. British Journal of Pharmacology 179(2): 301–321. https://doi.org/10.1111/bph.15702 [PubMed]

NagataY, Fujimoto M, NakamuraK, IsoyamaN, MatsumuraM, FujikawaK, UchiyamaK, TakakiE, TakiiR, Nakai A, MatsuyamaH (2016) Anti-TNF-αagent infliximab and splenectomy are protective against renal ischemia-reperfusion injury. Transplantation 100(8): 1675–1682. https://doi.org/10.1097/TP.0000000000001222 [PubMed]

Netrebenko AS, Gureev VV, Pokrovskii MV, Gureeva AV, Tsuverkalova YM, Rozhkov IS (2021) Assessment of the nephroprotective properties of the erythropoietin mimetic peptide and infliximab in kidney ischemia-reperfusion injury in rats. Archives of Razi Institute 76(4): 995–1004. https://doi.org/10.22092/ari.2021.355849.1728 [PubMed] [PMC]

NetrebenkoAS, GureevVV, PokrovskiiMV, YakushevVI, AvdeevaEV, GureevaAV, ZatolokinaMA (2022) Research of the renoprotective effect of a combination of the peptide mimicking the spatial structure of the b erythropoietin chain and infliximab in a renal ischemia-reperfusion injury model. Journal of Volgograd State Medical University [Vestnik Volgogradskogo Meditsinskogo Universiteta] 19(1): 167–172. https://doi.org/10.19163/1994-9480-2022-19-1-167-172 [in Russian]

Ponsioen CY, de Groof EJ, Eshuis EJ, Gardenbroek TJ, Bossuyt PMM, Hart A, Warusavitarne J, Buskens CJ, van Bodegraven AA, Brink MA, Consten ECJ, van Wagensveld BA, Rijk MCM, Crolla RMPH, Noomen CG, Houdijk APJ, Mallant RC, Boom M, Marsman WA, Stockmann HB, Mol B, de Groof AJ, Stokkers PC, D'Haens GR, Bemelman WA (2017) Laparoscopic ileocaecal resection versus infliximab for terminal ileitis in Crohn's disease: a randomised controlled, open-label, multicentre trial. The Lancet Gastroenterology and Hepatology 2(11): 785–792. https://doi.org/10.1016/S2468-1253(17)30248-0 [PubMed]

Ragulina VA, Kostina DA, Dovgan AP, Burda YE, Nadezhdin SV (2017) Nuclear factor kappa B as a potential target for pharmacological correction endothelium-associated pathology. Research Results in Pharmacology 3(1): 114–124. https://doi.org/10.18413/2500-235X-2017-3-1-114-124

Sabbisetti VS, Waikar SS, Antoine DJ, Smiles A, Wang C, Ravisankar A, Ito K, Sharma S, Ramadesikan S, Lee M, Briskin R, De Jager PL, Ngo TT, Radlinski M, Dear JW, Park KB, Betensky R, Krolewski AS, Bonventre JV (2014) Blood kidney injury molecule-1 is a biomarker of acute and chronic kidney injury and predicts progression to ESRD in type I diabetes. Journal of the American Society of Nephrology 25(10): 2177–2186. https://doi.org/10.1681/ASN.2013070758 [PubMed] [PMC]

Skachilova S, Danilenko L, Kesarev O, Kochkarova I (2015) Pharmacological protection of the ischemic myocardium by derivatives of 3-(2,2,2-trimethylhydrazinium) propionate and evaluation of their antioxidant activity. Research Results in Pharmacology 1(1): 23–27. https://doi.org/10.18413/2500-235X-2015-1-4-25-31

Tan R, Tian H, Yang B, Zhang B, Dai C, Han Z, Wang M, Li Y, Wei L, Chen D, Wang G, Yang H, He F, Chen Z (2018) Autophagy and Akt in the protective effect of erythropoietin helix B surface peptide against hepatic ischaemia/reperfusion injury in mice. Scientific Reports 8(1): 14703. https://doi.org/10.1038/s41598-018-33028-3 [PubMed] [PMC]

Tasdemir C, Tasdemir S, Vardi N, Ates B, Parlakpinar H, Kati B, Karaaslan MG, Acet A (2012) Protective effect of infliximab on ischemia/reperfusion-induced damage in rat kidney. Renal Failure 34(9): 1144–1149. https://dpo.org/10.3109/0886022X.2012.717490 [PubMed]

Wang W (2004) Renal potassium channels: recent developments. Current Opinion in Nephrology and Hypertension 13(5): 549–555. https://doi.org/10.1097/00041552-200409000-00011 [PubMed]

Yakovlev AK, L.A. GayderovaLA, AlpatovaNA, (2016) Studying of the standardization principles of pharmacological activity of recombinant erythropoietin preparations. Reference Materials 1: 8–20. https://doi.org/10.20915/2077-1177-2016-0-1-8-20

Zhang C, Yang C, Zhu T (2017) From erythropoietin to its peptide derivatives: Smaller but stronger. Current Protein &Peptide Science 18(12): 1191–1194. https://doi.org/10.2174/1389203717666160909130006 [PubMed]

Zhang X, Dong S (2019) Protective effects of erythropoietin towards acute lung injuries in rats with sepsis and its related mechanisms. Annals of Clinical and Laboratory Science 49(2): 257–264. [PubMed]

Author Biography

Aleksandr S. Netrebenko, Belgorod State National Research University

Postgraduate student, Department of Pharmacology and Clinical Pharmacology of Belgorod State National Research University,  e-mail: AlexNetrebenko@mail.com, ORCID ID https://orcid.org/0000-0003-2212-0508.  

Downloads

Published

19-06-2023

How to Cite

Netrebenko AS (2023) Correction of renal ischemia/reperfusion injury with the combination of Infliximab and the erythropoietin-derived peptide mimetic pHBSP. Research Results in Pharmacology 9(2): 85–97. https://doi.org/10.18413/rrpharmacology.9.10032

Issue

Section

Experimental Pharmacology