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Evaluation of Human Serum Albumin's Potential Effects on Renal Ischemia-Reperfusion Injury in a Rat Model

Year 2025, Volume: 20 Issue: 3, 130 - 138, 20.10.2025
https://doi.org/10.33719/nju1631647

Abstract

Objective: The purpose of this study is to examine how acute ischemia-reperfusion injury (IRI) in a rat model is affected by replacing human serum albumin (HSA).
Material and Methods: Thirty-six male Wistar albino rats were randomly divided into six groups: Control, Ischemia, Ischemia-Reperfusion (IR), Placebo, Preoperative Albumin (A1), and Intraoperative Albumin (A2). The renal artery of the kidney was blocked using 3/0 silk sutures to induce ischemia, followed by one hour of reperfusion in certain groups. The A1 group received 20% HSA (2.5 g/kg intraperitoneally) 24 hours before surgery, while the A2 group received the same dose 30 minutes before reperfusion. Samples of kidney and blood tissue were gathered for immunohistochemical, histological, and biochemical assessments. Biochemical parameters included ischemia-modified albumin (IMA), total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI). Histological assessments measured cortical and medullary damage, while immunohistochemistry evaluated oxidative stress markers such as superoxide dismutase (SOD1), glutathione reductase (GSR), and myeloperoxidase (MPO).
Results: Biochemical analyses showed no significant differences in TOS, TAS, OSI, and IMA levels between groups. Histological evaluation revealed that the A2 group had reduced kidney damage, particularly in the medulla, compared to the ischemia and placebo groups. Immunohistochemical findings indicated minor differences in oxidative stress marker expression, though not statistically significant.
Conclusion: Intraoperative HSA replacement has the potential to reduce ischemia-induced renal injury in rats, especially in medullary tissues. These findings suggest that HSA may be a promising therapeutic agent for managing ischemic kidney damage during partial nephrectomy. Further clinical studies are needed to validate its efficacy and safety in human applications.

Ethical Statement

Ethical approval for the project was obtained from the Kafkas University Animal Research Local Ethics Committee (decision date/number: 01-03-2023/2023-021).

Supporting Institution

This study was funded by the Kafkas University Scientific Research Projects Coordination Unit.

Project Number

TS-2023-58

Thanks

The authors thank Kafkas University Scientific Research Projects Coordination Unit.

References

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  • 6. Nørgård MØ, Svenningsen P. Acute Kidney Injury by Ischemia/Reperfusion and Extracellular Vesicles. Int J Mol Sci 2023;24. https://doi.org/10.3390/ IJMS242015312.
  • 7. Xie Z yong, Dong W, Zhang L, et al. NFAT inhibitor 11R-VIVIT ameliorates mouse renal fibrosis after ischemia-reperfusion-induced acute kidney injury. Acta Pharmacol Sin 2022;43:2081–2093. https://doi. org/10.1038/s41401-021-00833-y.
  • 8. Ma H, Guo X, Cui S, et al. Dephosphorylation of AMP-activated protein kinase exacerbates ischemia/ reperfusion-induced acute kidney injury via mitochondrial dysfunction. Kidney Int 2022;101:315– 330. https://doi.org/10.1016/j.kint.2021.10.028.
  • 9. Belinskaia DA, Voronina PA, Shmurak VI, Jenkins RO, Goncharov N V. Serum Albumin in Health and Disease: Esterase, Antioxidant, Transporting and Signaling Properties. Int J Mol Sci 2021;22. https://doi.org/10.3390/IJMS221910318.
  • 10. Chen X, Guan T, Li C, et al. SOD1 aggregation in astrocytes following ischemia/reperfusion injury: A role of NO-mediated S-nitrosylation of protein disulfide isomerase (PDI). J Neuroinflammation 2012;9:1–15. https://doi.org/10.1186/1742-2094-9-237/FIGURES/5.
  • 11. Chen S, Chen H, Du Q, Shen J. Targeting Myeloperoxidase (MPO) Mediated Oxidative Stress and Inflammation for Reducing Brain Ischemia Injury: Potential Application of Natural Compounds. Front Physiol 2020;11:528444. https://doi.org/10.3389/FPHYS.2020.00433/BIBTEX.
  • 12. Frasier CR, Moukdar F, Patel HD, et al. Redoxdependent increases in glutathione reductase and exercise preconditioning: role of NADPH oxidase and mitochondria. Cardiovasc Res 2013;98:47–55. https:// doi.org/10.1093/CVR/CVT009.
  • 13. Damiani E, Ince C, Orlando F, et al. Effects of the Infusion of 4% or 20% Human Serum Albumin on the Skeletal Muscle Microcirculation in Endotoxemic Rats. PLoS One 2016;11:e0151005. https://doi.org/10.1371/JOURNAL.PONE.0151005.
  • 14. Kahraman AA, Bingöl SA. Effects of Albumin Administration on Cytochrome C-1 (Cyc1) in IschemiaReperfusion Damaged Rat Ovary. Journal of Health Sciences 2024;33:175–181. https://doi.org/10.34108/ EUJHS.1345195.
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  • 16. Zakaria ER, Rippe B. Intraperitoneal fluid volume changes during peritoneal dialysis in the rat: Indicator dilution vs. volumetric measurements. Blood Purif 1995;13:255–270. https://doi.org/10.1159/000170209.
  • 17. Regoeczi E, Zaimi O, Chindemi PA, Charlwood PA. Absorption of plasma proteins from peritoneal cavity of normal rats. Am J Physiol Endocrinol Metab 1989;256. https://doi.org/10.1152/AJPENDO.1989.256.4.E447,.
  • 18. Watts JA, Maiorano PC. Trace Amounts of Albumin Protect Against Ischemia and Reperfusion Injury in Isolated Rat Hearts. J Mol Cell Cardiol 1999;31:1653– 1662. https://doi.org/10.1006/jmcc.1999.1001.
  • 19. Sampaio de Holanda G, dos Santos Valença S, Maran Carra A, et al. Sulforaphane and Albumin Attenuate Experimental Intestinal Ischemia-Reperfusion Injury. Journal of Surgical Research 2021;262:212–223. https://doi.org/10.1016/J.JSS.2021.01.014.
  • 20. Tang Y, Shen J, Zhang F, Yang FY, Liu M. Human serum albumin attenuates global cerebral ischemia/ reperfusion-induced brain injury in a Wnt/β-Catenin/ ROS signaling-dependent manner in rats. Biomedicine & Pharmacotherapy 2019;115:108871. https://doi. org/10.1016/J.BIOPHA.2019.108871.
  • 21. Kisaoglu A, Kose E, Yilmaz N, et al. Investigation of the Effect of Astaxanthin on Autophagy in Renal Ischemia-reperfusion Modeled Rats. Medeni Med J 2024;39:101–108. https://doi.org/10.4274/MMJ. GALENOS.2024.27243.
  • 22. Guzeloglu M, Yalcinkaya F, Atmaca S, et al. The beneficial effects of tadalafil on renal ischemia-reperfusion injury in rats. Urol Int 2011;86:197–203. https://doi. org/10.1159/000321927.
  • 23. Sarac F, Kilincaslan H, Kilic E, Koldas M, Terzi EH, Aydogdu I. Methylene blue attenuates renal ischemia– reperfusion injury in rats. J Pediatr Surg 2015;50:1067– 1071. https://doi.org/10.1016/J.JPEDSURG.2014.06.018.
  • 24. Aytac Ates H, Yücetaş U, Erkan E, et al. The Predictive Value of Ischemia-Modified Albumin in Renal IschemiaReperfusion Injury. Urol Int 2019;103:473–481. https:// doi.org/10.1159/000500929.
  • 25. Wu B, Yu J, Luo Y, Wu L, Zhang Z, Deng L. An Albumin-Enriched Nanocomplex Achieves Systemic Delivery of Clopidogrel Bisulfate to Ameliorate Renal Ischemia Reperfusion Injury in Rats. Mol Pharm 2022;19:3934–3947. https://doi.org/10.1021/acs. molpharmaceut.2c00401.
  • 26. Zabell JR, Wu J, Suk-Ouichai C, Campbell SC. Renal Ischemia and Functional Outcomes Following Partial Nephrectomy. Urol Clin North Am 2017;44:243–255. https://doi.org/10.1016/J.UCL.2016.12.010.
  • 27. Ellmerer M, Schaupp L, Brunner GA, et al. Measurement of interstitial albumin in human skeletal muscle and adipose tissue by open-flow microperfusion. Am J Physiol Endocrinol Metab 2000;278. https://doi.org/10.1152/AJPENDO.2000.278.2.E352/ASSET/ IMAGES/LARGE/AEND10224003X.JPEG.
  • 28. Brock F, Bettinelli LA, Dobner T, Stobbe JC, Pomatti G, Telles CT. Prevalence of hypoalbuminemia and nutritional issues in hospitalized elders. Rev Lat Am Enfermagem 2016;24. https://doi.org/10.1590/1518-8345.0260.2736.
  • 29. Karakiewicz PI, Jeldres C, Suardi N, et al. Age at diagnosis is a determinant factor of renal cell carcinoma–specific survival in patients treated with nephrectomy. Canadian Urological Association Journal 2008;2:610. https://doi. org/10.5489/CUAJ.978.

Evaluation of Human Serum Albumin's Potential Effects on Renal Ischemia-Reperfusion Injury in a Rat Model

Year 2025, Volume: 20 Issue: 3, 130 - 138, 20.10.2025
https://doi.org/10.33719/nju1631647

Abstract

Project Number

TS-2023-58

References

  • 1. Capitanio U, Montorsi F. Renal cancer. The Lancet 2016;387:894–906. https://doi.org/10.1016/S0140- 6736(15)00046-X.
  • 2. Drucker BJ. Renal cell carcinoma: Current status and future prospects. Cancer Treat Rev 2005;31:536–545. https://doi.org/10.1016/J.CTRV.2005.07.009.
  • 3. Delahunt B, Eble JN, Samaratunga H, Thunders M, Yaxley JW, Egevad L. Staging of renal cell carcinoma: current progress and potential advances. Pathology 2021;53:120– 128. https://doi.org/10.1016/J.PATHOL.2020.08.007.
  • 4. Ljungberg B, Albiges L, Abu-Ghanem Y, et al. European Association of Urology Guidelines on Renal Cell Carcinoma: The 2022 Update. Eur Urol 2022;82:399– 410. https://doi.org/10.1016/J.EURURO.2022.03.006.
  • 5. Deutch MR, Dreyer TK, Pelant T, Jensen JB. Impact of ischemia time during partial nephrectomy on short- and long-term renal function. Scand J Urol 2023;57:86–89. https://doi.org/10.1080/21681805.2023.2172075.
  • 6. Nørgård MØ, Svenningsen P. Acute Kidney Injury by Ischemia/Reperfusion and Extracellular Vesicles. Int J Mol Sci 2023;24. https://doi.org/10.3390/ IJMS242015312.
  • 7. Xie Z yong, Dong W, Zhang L, et al. NFAT inhibitor 11R-VIVIT ameliorates mouse renal fibrosis after ischemia-reperfusion-induced acute kidney injury. Acta Pharmacol Sin 2022;43:2081–2093. https://doi. org/10.1038/s41401-021-00833-y.
  • 8. Ma H, Guo X, Cui S, et al. Dephosphorylation of AMP-activated protein kinase exacerbates ischemia/ reperfusion-induced acute kidney injury via mitochondrial dysfunction. Kidney Int 2022;101:315– 330. https://doi.org/10.1016/j.kint.2021.10.028.
  • 9. Belinskaia DA, Voronina PA, Shmurak VI, Jenkins RO, Goncharov N V. Serum Albumin in Health and Disease: Esterase, Antioxidant, Transporting and Signaling Properties. Int J Mol Sci 2021;22. https://doi.org/10.3390/IJMS221910318.
  • 10. Chen X, Guan T, Li C, et al. SOD1 aggregation in astrocytes following ischemia/reperfusion injury: A role of NO-mediated S-nitrosylation of protein disulfide isomerase (PDI). J Neuroinflammation 2012;9:1–15. https://doi.org/10.1186/1742-2094-9-237/FIGURES/5.
  • 11. Chen S, Chen H, Du Q, Shen J. Targeting Myeloperoxidase (MPO) Mediated Oxidative Stress and Inflammation for Reducing Brain Ischemia Injury: Potential Application of Natural Compounds. Front Physiol 2020;11:528444. https://doi.org/10.3389/FPHYS.2020.00433/BIBTEX.
  • 12. Frasier CR, Moukdar F, Patel HD, et al. Redoxdependent increases in glutathione reductase and exercise preconditioning: role of NADPH oxidase and mitochondria. Cardiovasc Res 2013;98:47–55. https:// doi.org/10.1093/CVR/CVT009.
  • 13. Damiani E, Ince C, Orlando F, et al. Effects of the Infusion of 4% or 20% Human Serum Albumin on the Skeletal Muscle Microcirculation in Endotoxemic Rats. PLoS One 2016;11:e0151005. https://doi.org/10.1371/JOURNAL.PONE.0151005.
  • 14. Kahraman AA, Bingöl SA. Effects of Albumin Administration on Cytochrome C-1 (Cyc1) in IschemiaReperfusion Damaged Rat Ovary. Journal of Health Sciences 2024;33:175–181. https://doi.org/10.34108/ EUJHS.1345195.
  • 15. Anesthesia (Guideline) | Vertebrate Animal Research. Available at https://animal.research.uiowa.edu/iacucguidelines-anesthesia. Accessed November 25, 2024.
  • 16. Zakaria ER, Rippe B. Intraperitoneal fluid volume changes during peritoneal dialysis in the rat: Indicator dilution vs. volumetric measurements. Blood Purif 1995;13:255–270. https://doi.org/10.1159/000170209.
  • 17. Regoeczi E, Zaimi O, Chindemi PA, Charlwood PA. Absorption of plasma proteins from peritoneal cavity of normal rats. Am J Physiol Endocrinol Metab 1989;256. https://doi.org/10.1152/AJPENDO.1989.256.4.E447,.
  • 18. Watts JA, Maiorano PC. Trace Amounts of Albumin Protect Against Ischemia and Reperfusion Injury in Isolated Rat Hearts. J Mol Cell Cardiol 1999;31:1653– 1662. https://doi.org/10.1006/jmcc.1999.1001.
  • 19. Sampaio de Holanda G, dos Santos Valença S, Maran Carra A, et al. Sulforaphane and Albumin Attenuate Experimental Intestinal Ischemia-Reperfusion Injury. Journal of Surgical Research 2021;262:212–223. https://doi.org/10.1016/J.JSS.2021.01.014.
  • 20. Tang Y, Shen J, Zhang F, Yang FY, Liu M. Human serum albumin attenuates global cerebral ischemia/ reperfusion-induced brain injury in a Wnt/β-Catenin/ ROS signaling-dependent manner in rats. Biomedicine & Pharmacotherapy 2019;115:108871. https://doi. org/10.1016/J.BIOPHA.2019.108871.
  • 21. Kisaoglu A, Kose E, Yilmaz N, et al. Investigation of the Effect of Astaxanthin on Autophagy in Renal Ischemia-reperfusion Modeled Rats. Medeni Med J 2024;39:101–108. https://doi.org/10.4274/MMJ. GALENOS.2024.27243.
  • 22. Guzeloglu M, Yalcinkaya F, Atmaca S, et al. The beneficial effects of tadalafil on renal ischemia-reperfusion injury in rats. Urol Int 2011;86:197–203. https://doi. org/10.1159/000321927.
  • 23. Sarac F, Kilincaslan H, Kilic E, Koldas M, Terzi EH, Aydogdu I. Methylene blue attenuates renal ischemia– reperfusion injury in rats. J Pediatr Surg 2015;50:1067– 1071. https://doi.org/10.1016/J.JPEDSURG.2014.06.018.
  • 24. Aytac Ates H, Yücetaş U, Erkan E, et al. The Predictive Value of Ischemia-Modified Albumin in Renal IschemiaReperfusion Injury. Urol Int 2019;103:473–481. https:// doi.org/10.1159/000500929.
  • 25. Wu B, Yu J, Luo Y, Wu L, Zhang Z, Deng L. An Albumin-Enriched Nanocomplex Achieves Systemic Delivery of Clopidogrel Bisulfate to Ameliorate Renal Ischemia Reperfusion Injury in Rats. Mol Pharm 2022;19:3934–3947. https://doi.org/10.1021/acs. molpharmaceut.2c00401.
  • 26. Zabell JR, Wu J, Suk-Ouichai C, Campbell SC. Renal Ischemia and Functional Outcomes Following Partial Nephrectomy. Urol Clin North Am 2017;44:243–255. https://doi.org/10.1016/J.UCL.2016.12.010.
  • 27. Ellmerer M, Schaupp L, Brunner GA, et al. Measurement of interstitial albumin in human skeletal muscle and adipose tissue by open-flow microperfusion. Am J Physiol Endocrinol Metab 2000;278. https://doi.org/10.1152/AJPENDO.2000.278.2.E352/ASSET/ IMAGES/LARGE/AEND10224003X.JPEG.
  • 28. Brock F, Bettinelli LA, Dobner T, Stobbe JC, Pomatti G, Telles CT. Prevalence of hypoalbuminemia and nutritional issues in hospitalized elders. Rev Lat Am Enfermagem 2016;24. https://doi.org/10.1590/1518-8345.0260.2736.
  • 29. Karakiewicz PI, Jeldres C, Suardi N, et al. Age at diagnosis is a determinant factor of renal cell carcinoma–specific survival in patients treated with nephrectomy. Canadian Urological Association Journal 2008;2:610. https://doi. org/10.5489/CUAJ.978.
There are 29 citations in total.

Details

Primary Language English
Subjects Urology
Journal Section Research Article
Authors

Ümit Yıldırım

Mehmet Uslu 0000-0002-8370-3793

Mehmet Ezer 0000-0003-4422-6768

İsmet Bilger Erihan

Ali Alper Kahraman

Seyit Ali Bingöl

Project Number TS-2023-58
Publication Date October 20, 2025
Submission Date February 2, 2025
Acceptance Date August 6, 2025
Published in Issue Year 2025 Volume: 20 Issue: 3

Cite

Vancouver Yıldırım Ü, Uslu M, Ezer M, Erihan İB, Kahraman AA, Bingöl SA. Evaluation of Human Serum Albumin’s Potential Effects on Renal Ischemia-Reperfusion Injury in a Rat Model. New J Urol. 2025;20(3):130-8.