Renoprotective potential of exogen erythropoietin on experimental ruptured abdominal aortic aneurysm model: An animal study

Document Type: Original Article


1 Department of Cardiovascular Surgery, Faculty of Medicine, Karadeniz Technical University, 61080 Trabzon, Turkey

2 Department of Histology and Embryology, Faculty of Medicine, Karadeniz Technical University, 61080 Trabzon, Turkey

3 Department of Biochemistry, Faculty of Medicine, Karadeniz Technical University, 61080 Trabzon, Turkey


Objective(s): The aim of this study is to investigate the renoprotective effect of erythropoietin (EPO) on hypovolemic shock and ischemia/reperfusion (IR) injury on kidneys as end-organs in an experimentally-created ruptured abdominal aortic aneurysm (rAAA) model.
Materials and Methods: Thirty anesthetized Sprague-Dawley male rats were randomized to sham ((Sh n:6) (Sh+EPO n:6)) or shock and I/R groups ((S/IR n:9) (S/IR+EPO n:9)). Additional surgical procedure except aortic exploration was not performed on Sh and Sh+EPO groups. 60 min of shock, 60 min of ischemia, and 120 min of reperfusion were applied on S/IR and S/IR+EPO groups. In the S/IR and S/IR+EPO groups, hemorrhagic shock, lower torso ischemia, and reperfusion were created. At the end of the shock period, saline solutions were separately and equally administered to Sh and S/IR groups, whereas 2000 U/kg EPO was intraperitoneally administered to Sh+EPO and S/IR+EPO groups. At the end of the experimental study, some biochemical and histological parameters were studied in serum and kidney tissues.
Results: Biochemical parameters were all significantly increased in the S/IR group compared with the Sh group. These parameters were not statistically significantly different between S/IR+EPO and Sh+EPO groups. In histopathologic examination, EPO prevented high-grade injury.
Conclusion: Our data indicate that EPO may have a renoprotective effect and reduce the systemic inflammatory response that resulted from shock and I/R in an experimental model of rAAA.


1. Böckler D, Holden A, Krievins D, de Vries JP, Peters AS, Geisbüsch P, et al. Extended use of endovascular aneurysm sealing for ruptured abdominal aortic aneurysms. Semin Vasc Surg 2016; 29: 106-113.
2. An endovascular strategy or open repair for ruptured abdominal aortic aneurysm: one-year outcomes from the IMPROVE randomised trial. Eur Heart J 2015; 36: 2061-2069.
3. Eslami MH, Messina LM. Ruptured AAA: open surgical management. Semin Vasc Surg 2010; 23: 200-205.
4. Lindsay TF, Walker P, Romaschin A. Acute pulmonary injury in a model of ruptured abdominal aortic aneurysm. J Vasc Surg 1995; 22:1-8.
5. Ishii Y, Sawada T, Murakami T, Sakuraoka Y, Shiraki T, Shimizu A, et al. Renoprotective effect of erythropoietin against ischemia-reperfusion injury in non-human primate model. Nephrol Dial Transplant 2011; 26:1157-1162.
6. Song YR, Lee T, You SJ, Chin HJ, Chae DW, Lim C, et al. Prevention of acute kidney injury by erythropoietin in patients undergoing coronary artery bypass grafting: A pilot study. Am J Nephrol 2009; 30: 253-260.
7. Moeini M, Nematbakhsh M, Fazilati M, Talebi A, Pilehvarian AA, Azarkish F, et al. Protective role of recombinant human erythropoietin in kidney and lung injury following renal bilateral ischemia-reperfusion in rat model. Int J Prev Med 2013;4:648-655.
8. Lombardero M, Kovacs K, Scheithauer BW. Erythropoietin: a hormone with multiple functions. Pathobiology 2011;78:41-53.
9. K. Yagi. Assay for blood plasma or serum. Methods Enzymol 1984; 105: 328–331.
10. Mihara M, Uchiyama M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem 1978;86:271-278.
11. Tahamtan M, Moosavi SM, Sheibani V, Nayebpour M, Esmaeili-Mahani S, Shabani M. Erythropoietin attenuates motor impairments induced by bilateral renal ischemia/reperfusion in rats. Fundam Clin Pharmacol 2016;30:502-510.
12. Nandra KK, Collino M, Rogazzo M, Fantozzi R, Patel NS, Thiemermann C. Pharmacological preconditioning with erythropoietin attenuates the organ injury and dysfunction induced in a rat model of hemorrhagic shock. Dis Model Mech 2013;6:701-709.
13. Seifi B, Kadkhodaee M, Ranjbaran M, Bakhshi E. Nephroprotection through the Akt/eNOS pathway by centrally administered erythropoietin in a rat model of fixed-volume hemorrhage. Life Sci 2018; 193:180-185.
14. Zhang J, Zhao D, Na N, Li H, Miao B, Hong L, et al. Renoprotective effect of erythropoietin via modulation of the STAT6/MAPK/NF-κB pathway in ischemia/reperfusion injury after renal transplantation. Int J Mol Med 2018;41:25-32.
15. Kiss K, Csonka C, Pálóczi J, Pipis J, Görbe A, Kocsis GF et al. Novel, selective EPO receptor ligands lacking erythropoietic activity reduce infarct size in acute myocardial infarction in rats. Pharmacol Res 2016;113:62-70.
16. Elshiekh M, Kadkhodaee M, Seifi B, Ranjbaran M, Ahghari P. Ameliorative Effect of recombinant human erythropoietin and ıschemic preconditioning on renal ıschemia-reperfusion ınjury in rats. Nephrourol Mon 2015;7: e31152.