Impact of inhaled oxygen on reactive oxygen species production and oxidative damage during spontaneous ventilation in a murine model of acute renal ischemia and reperfusion

Main Article Content

Melissa J. Kimlinger Eric H. Mace, MD Raymond C. Harris, MD Ming-Zhi Zhang, MD Matthew B. Barajas, MD Antonio Hernandez, MD, MSc Frederic T. Billings, IV, MD, MSc

Abstract

Introduction: Acute kidney injury (AKI) affects 10% of patients following major surgery and is independently associated with extra-renal organ injury, development of chronic kidney disease, and death. Perioperative renal ischemia and reperfusion (IR) contributes to AKI by, in part, increasing production of reactive oxygen species (ROS) and leading to oxidative damage. Variations in inhaled oxygen may mediate some aspects of IR injury by affecting tissue oxygenation, ROS production, and oxidative damage. We tested the hypothesis that provision of air (normoxia) compared to 100% oxygen (hyperoxia) during murine renal IR affects renal ROS production and oxidative damage.


Methods: We administered 100% oxygen or air to 8-9 week-old FVB/N mice and performed dorsal unilateral nephrectomy with contralateral renal ischemia/reperfusion surgery while mice spontaneously ventilated. We subjected mice to 30 minutes of ischemia and 30 minutes of reperfusion prior to sacrifice. We obtained an arterial blood gas (ABG) by performing sternotomy and left cardiac puncture. We stained the kidney with pimonidazole, a marker of tissue hypoxia; 4-HNE, a marker of ROS-production; and measured F 2 -isoprostanes in homogenized tissue to quantify oxidative damage.


Results: Hyperoxia during IR increased arterial oxygen content compared to normoxia, but both groups of mice were hypoventilating at the time of ABG sampling. Renal tissue hypoxia following reperfusion was similar in both treatment groups. ROS production was similar in the cortex of mice (3.8% area in hyperoxia vs. 3.1% in normoxia, P=0.19) but increased in the medulla of hyperoxia-treated animals (6.3% area in hyperoxia vs. 4.5% in nomoxia, P=0.02). Renal F 2 -isoprostanes were similar in treatment groups (2.2 pg/mg kidney in hyperoxia vs. 2.1 pg/mg in normoxia, P=0.40).


Conclusions: Hyperoxia during spontaneous ventilation in murine renal IR did not appear to affect renal hypoxia following reperfusion, but hyperoxia increased medullary ROS production compared to normoxia.


Key Words: kidney, AKI, oxygen, ischemia, reperfusion, oxidative damage, organ injury, normoxia, hyperoxia, hypoxia, FIO2, murine

Article Details

How to Cite
KIMLINGER, Melissa J. et al. Impact of inhaled oxygen on reactive oxygen species production and oxidative damage during spontaneous ventilation in a murine model of acute renal ischemia and reperfusion. Medical Research Archives, [S.l.], v. 9, n. 10, oct. 2021. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/2575>. Date accessed: 28 nov. 2021. doi: https://doi.org/10.18103/mra.v9i10.2575.
Section
Research Articles

References

1. Chertow GM, Burdick E, Honour M, Bonventre JV, Bates DW. Acute Kidney Injury, Mortality, Length of Stay, and Costs in Hospitalized Patients. 2005-11-01 2005;doi:10.1681/ASN.2004090740
2. Fortrie G, de Geus HRH, Betjes MGH. The aftermath of acute kidney injury: a narrative review of long-term mortality and renal function. ReviewPaper. Critical Care. 2019-01-24 2019;23(1):1-11. doi:doi:10.1186/s13054-019-2314-z
3. Meersch M, Schmidt C, Zarbock A. Perioperative Acute Kidney Injury: An Under-Recognized Problem. Anesthesia and analgesia. 2017 Oct 2017;125(4)doi:10.1213/ANE.0000000000002369
4. Molinari L, Sakhuja A, Kellum JA. Perioperative Renoprotection: General Mechanisms and Treatment Approaches. Anesthesia & Analgesia. 2020;131(6)
5. Saadat-Gilani K, Zarbock A, Meersch M. Perioperative Renoprotection: Clinical Implications. Anesthesia & Analgesia. 2020;131(6)
6. O'Neal J, Shaw A, Billings F. Acute kidney injury following cardiac surgery: current understanding and future directions. Critical care (London, England). 07/04/2016 2016;20(1)doi:10.1186/s13054-016-1352-z
7. Conrad C, Eltzschig HK. Disease Mechanisms of Perioperative Organ Injury. Anesthesia & Analgesia. 2020;131(6)
8. Mouren S, Souktani R, Beaussier M, et al. Mechanisms of coronary vasoconstriction induced by high arterial oxygen tension. Am J Physiol. Jan 1997;272(1 Pt 2):H67-75. doi:10.1152/ajpheart.1997.272.1.H67
9. Smit B, Smulders YM, van der Wouden JC, Oudemans-van Straaten HM, Spoelstra-de Man AME. Hemodynamic effects of acute hyperoxia: systematic review and meta-analysis. ReviewPaper. Critical Care. 2018-02-25 2018;22(1):1-10. doi:doi:10.1186/s13054-018-1968-2
10. Cadenas S. ROS and redox signaling in myocardial ischemia-reperfusion injury and cardioprotection. Free radical biology & medicine. 2018 Mar 2018;117doi:10.1016/j.freeradbiomed.2018.01.024
11. Granger D, Kvietys P. Reperfusion injury and reactive oxygen species: The evolution of a concept. Redox biology. 2015 Dec 2015;6doi:10.1016/j.redox.2015.08.020
12. Meng-Yu W, Giou-Teng Y, Wan-Ting L, et al. Current Mechanistic Concepts in Ischemia and Reperfusion Injury. Cellular Physiology and Biochemistry. 2021;46(4):1650-1667. doi:10.1159/000489241
13. Grocott HP, Faraoni D. Avoidance of Hyperoxemia during Cardiopulmonary Bypass: Why Does Pathophysiology Not Always Translate into Clinical Outcome? Anesthesiology. 2021;128(2):419-419. doi:10.1097/ALN.0000000000001990
14. Nensén O, Hansell P, Palm F. Intrarenal oxygenation determines kidney function during the recovery from an ischemic insult. American journal of physiology Renal physiology. 12/01/2020 2020;319(6)doi:10.1152/ajprenal.00162.2020
15. Chouchani ET, Pell VR, Gaude E, et al. Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature. 2014/11/01 2014;515(7527):431-435. doi:10.1038/nature13909
16. Eltzschig HK, Eckle T. Ischemia and reperfusion—from mechanism to translation. Nature Medicine. 2011/11/01 2011;17(11):1391-1401. doi:10.1038/nm.2507
17. Skrypnyk NI, Harris RC, de Caestecker MP. Ischemia-reperfusion model of acute kidney injury and post injury fibrosis in mice. J Vis Exp. Aug 9 2013;(78)doi:10.3791/50495
18. Varia M, Calkins-Adams D, Rinker L, et al. Pimonidazole: a novel hypoxia marker for complementary study of tumor hypoxia and cell proliferation in cervical carcinoma. Gynecologic oncology. 1998 Nov 1998;71(2)doi:10.1006/gyno.1998.5163
19. Dalleau S, Baradat M, Guéraud F, Huc L. Cell death and diseases related to oxidative stress:4-hydroxynonenal (HNE) in the balance. Cell Death & Differentiation. 2013/12/01 2013;20(12):1615-1630. doi:10.1038/cdd.2013.138
20. Milne GL, Musiek ES, Morrow JD. F2-isoprostanes as markers of oxidative stress in vivo: an overview. Biomarkers. Nov 2005;10 Suppl 1:S10-23. doi:10.1080/13547500500216546
21. Milne G, Sanchez S, Musiek E, Morrow J. Quantification of F2-isoprostanes as a biomarker of oxidative stress. Nature protocols. 2007 2007;2(1)doi:10.1038/nprot.2006.375
22. Iversen N, Malte H, Baatrup E, Wang T. The normal acid-base status of mice. Respiratory physiology & neurobiology. 03/15/2012 2012;180(2-3)doi:10.1016/j.resp.2011.11.015
23. Massey CA, Richerson GB. Isoflurane, ketamine-xylazine, and urethane markedly alter breathing even at subtherapeutic doses. J Neurophysiol. 2017;118(4):2389-2401. doi:10.1152/jn.00350.2017
24. Munshi R, Hsu C, Himmelfarb J. Advances in understanding ischemic acute kidney injury. ReviewPaper. BMC Medicine. 2011-02-02 2011;9(1):1-6. doi:doi:10.1186/1741-7015-9-11
25. Molitoris B, Sandoval R, Sutton T. Endothelial injury and dysfunction in ischemic acute renal failure. Critical care medicine. 2002 May 2002;30(5 Suppl)doi:10.1097/00003246-200205001-00011
26. Zwemer CF, Shoemaker JL, Jr., Hazard SW, 3rd, Davis RE, Bartoletti AG, Phillips CL. Hyperoxic reperfusion exacerbates postischemic renal dysfunction. Surgery. Nov 2000;128(5):815-21. doi:10.1067/msy.2000.109117