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Administration of hydrogen sulfide protects ischemia reperfusion-induced acute kidney injury by reducing the oxidative stress

Abstract

Background

Renal ischemia–reperfusion injury (IRI) is a major cause of acute kidney injury. Hydrogen sulfide (H2S) has been known as a novel gaseous signaling molecule.

Aims

The aim of this study was to investigate whether the efficacy of H2S in protecting against renal IRI is through its antioxidative effect.

Method

In this study, rats were randomized into Sham, IR, or sodium hydrosulfide (NaHS, an H2S donor) groups. To establish a model of renal IRI, both renal arteries were occluded for 55 min and then declamped to allow reperfusion for 24 h. Rats in the NaHS group received intraperitoneal injections of 75 μmol/kg NaHS 10 min before the onset of ischemia and immediately after the onset of reperfusion. Sham group underwent laparotomy without cross-clamping of renal pedicles. After reperfusion, plasma and renal tissue samples were collected for functional, histological, and oxidative stress evaluation.

Results

The IR group exhibited significant rise in plasma creatinine, blood urea nitrogen (BUN), renal malondialdehyde (MDA) concentration, and significant reduction of renal superoxide dismutase (SOD) activity. Treatment with NaHS reduced the levels of plasma creatinine, BUN, renal MDA concentration, and increased SOD activity in the kidneys. NaHS improved renal histological changes in comparison to IR group.

Conclusion

Our data demonstrated that H2S can protect against renal IRI and that its therapeutic effects may be mediated by reducing oxidative stress.

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References

  1. Chertow GM, Burdick E, Honour M, Bonventre JV, Bates DW (2005) Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol 16:3365–3370

    Article  PubMed  Google Scholar 

  2. Regner KR, Roman RJ (2012) Role of medullary blood flow in the pathogenesis of renal ischemia-reperfusion injury. Curr Opin Nephrol Hypertens 21:33–38

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  3. Tan S, Wang G, Guo Y, Gui D, Wang N (2013) Preventive effects of a natural anti-inflammatory agent, astragaloside IV, on ischemic acute kidney injury in rats. Evid Based Complement Alternat Med 2013:284025

    PubMed  PubMed Central  Google Scholar 

  4. Hunter JP, Hosgood SA, Patel M, Rose R, Read K, Nicholson ML (2012) Effects of hydrogen sulphide in an experimental model of renal ischaemia-reperfusion injury. Br J Surg 99:1665–1671

    CAS  Article  PubMed  Google Scholar 

  5. Hosgood SA, Nicholson ML (2010) Hydrogen sulphide ameliorates ischaemia-reperfusion injury in an experimental model of non-heart-beating donor kidney transplantation. Br J Surg 97:202–209

    CAS  Article  PubMed  Google Scholar 

  6. Williams P, Lopez H, Britt D, Chan C, Ezrin A, Hottendorf R (1997) Characterization of renal ischemia-reperfusion injury in rats. J Pharmacol Toxicol Methods 37:1–7

    CAS  Article  PubMed  Google Scholar 

  7. Kurian GA, Pemaih B (2014) Standardization of in vitro cell-based model for renal ischemia and reperfusion injury. Indian J Pharm Sci 76:348–353

    PubMed  PubMed Central  Google Scholar 

  8. Singh D, Kaur R, Chander V, Chopra K (2006) Antioxidants in the prevention of renal disease. J Med Food 9:443–450

    CAS  Article  PubMed  Google Scholar 

  9. Pham-Huy LA, He H, Pham-Huy C (2008) Free radicals, antioxidants in disease and health. Int J Biomed Sci 4:89–96

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Yun Y, Duan WG, Chen P, Wu HX, Shen ZQ, Qian ZY et al (2009) Ischemic postconditioning modified renal oxidative stress and lipid peroxidation caused by ischemic reperfusion injury in rats. Transplant Proc 41:3597–3602

    CAS  Article  PubMed  Google Scholar 

  11. Davies KJ (1987) Protein damage and degradation by oxygen radicals. I. general aspects. J Biol Chem 262:9895–9901

    CAS  PubMed  Google Scholar 

  12. Ivanov AV, Bartosch B, Smirnova OA, Isaguliants MG, Kochetkov SN (2013) HCV and oxidative stress in the liver. Viruses 5:439–469

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. Ferrari R, Ceconi C, Curello S, Cargnoni A, Pasini E, De Giuli F et al (1991) Role of oxygen free radicals in ischemic and reperfused myocardium. Am J Clin Nutr 53:215S–222S

    CAS  PubMed  Google Scholar 

  14. Paller MS, Hoidal JR, Ferris TF (1984) Oxygen free radicals in ischemic acute renal failure in the rat. J Clin Invest 74:1156–1164

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. Wallace JL, Blackler RW, Chan MV, Da Silva GJ, Elsheikh W, Flannigan KL et al (2015) Anti-inflammatory and cytoprotective actions of hydrogen sulfide: translation to therapeutics. Antioxid Redox Signal 22(5):398–410

    CAS  Article  PubMed  Google Scholar 

  16. King AL, Lefer DJ (2011) Cytoprotective actions of hydrogen sulfide in ischaemia-reperfusion injury. Exp Physiol 96:840–846

    CAS  Article  PubMed  Google Scholar 

  17. Bracht H, Scheuerle A, Groger M, Hauser B, Matallo J, McCook O et al (2012) Effects of intravenous sulfide during resuscitated porcine hemorrhagic shock*. Crit Care Med 40:2157–2167

    CAS  Article  PubMed  Google Scholar 

  18. Xue H, Yuan P, Ni J, Li C, Shao D, Liu J et al (2013) H(2)S inhibits hyperglycemia-induced intrarenal renin-angiotensin system activation via attenuation of reactive oxygen species generation. PLoS ONE 8:e74366

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. Esterbauer H, Schaur RJ, Zollner H (1991) Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med 11:81–128

    CAS  Article  PubMed  Google Scholar 

  20. Paoletti F, Mocali A (1990) Determination of superoxide dismutase activity by purely chemical system based on NAD (P) H Oxidation. Methods Enzymol 186:209–220

    CAS  Article  PubMed  Google Scholar 

  21. Elrod JW, Calvert JW, Morrison J, Doeller JE, Kraus DW, Tao L et al (2007) Hydrogen sulfide attenuates myocardial ischemia-reperfusion injury by preservation of mitochondrial function. Proc Natl Acad Sci USA 104:15560–15565

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  22. Hunter J, Hosgood S, Patel M, Rose R, Read K, Nicholson M (2012) Effects of hydrogen sulphide in an experimental model of renal ischaemia–reperfusion injury. Br J Surg 99:1665–1671

    CAS  Article  PubMed  Google Scholar 

  23. Ekici F, Karson A, Dillioglugil MO, Gurol G, Kir HM, Ates N (2013) The effects of vagal nerve stimulation in focal cerebral ischemia and reperfusion model. Turk Neurosurg 23:451–457

    PubMed  Google Scholar 

  24. Bos EM, Wang R, Snijder PM, Boersema M, Damman J, Fu M et al (2013) Cystathionine gamma-lyase protects against renal ischemia/reperfusion by modulating oxidative stress. J Am Soc Nephrol 24:759–770

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  25. Bos EM, Leuvenink HG, Snijder PM, Kloosterhuis NJ, Hillebrands JL, Leemans JC et al (2009) Hydrogen sulfide-induced hypometabolism prevents renal ischemia/reperfusion injury. J Am Soc Nephrol 20:1901–1905

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  26. Tripatara P, Patel NS, Brancaleone V, Renshaw D, Rocha J, Sepodes B et al (2009) Characterisation of cystathionine gamma-lyase/hydrogen sulphide pathway in ischaemia/reperfusion injury of the mouse kidney: an in vivo study. Eur J Pharmacol 606:205–209

    CAS  Article  PubMed  Google Scholar 

  27. Kim J, Jang HS, Park KM (2010) Reactive oxygen species generated by renal ischemia and reperfusion trigger protection against subsequent renal ischemia and reperfusion injury in mice. Am J Physiol Renal Physiol 298:F158–F166

    CAS  Article  PubMed  Google Scholar 

  28. Xu Z, Prathapasinghe G, Wu N, Hwang SY, Siow YL (2009) O K. Ischemia-reperfusion reduces cystathionine-beta-synthase-mediated hydrogen sulfide generation in the kidney. Am J Physiol Renal Physiol 297:F27–F35

    CAS  Article  PubMed  Google Scholar 

  29. Liu H, Bai XB, Shi S, Cao YX (2009) Hydrogen sulfide protects from intestinal ischaemia–reperfusion injury in rats. J Pharm Pharmacol 61:207–212

    CAS  Article  PubMed  Google Scholar 

  30. Zhou X, Feng Y, Zhan Z, Chen J (2014) Hydrogen sulfide alleviates diabetic nephropathy in a streptozotocin-induced diabetic rat model. J Biol Chem 289:28827–28834

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. Liu H, Bai XB, Shi S, Cao YX (2009) Hydrogen sulfide protects from intestinal ischaemia-reperfusion injury in rats. J Pharm Pharmacol 61:207–212

    CAS  Article  PubMed  Google Scholar 

  32. Cheng P, Wang F, Chen K, Shen M, Dai W, Xu L et al (2014) Hydrogen sulfide ameliorates ischemia/reperfusion-induced hepatitis by inhibiting apoptosis and autophagy pathways. Mediators Inflamm 2014:935251

    PubMed  PubMed Central  Google Scholar 

  33. Webster KA (2012) Mitochondrial membrane permeabilization and cell death during myocardial infarction: roles of calcium and reactive oxygen species. Future Cardiol 8:863–884

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  34. Wang JF, Li Y, Song JN, Pang HG (2014) Role of hydrogen sulfide in secondary neuronal injury. Neurochem Int 64:37–47

    CAS  Article  PubMed  Google Scholar 

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Azizi, F., Seifi, B., Kadkhodaee, M. et al. Administration of hydrogen sulfide protects ischemia reperfusion-induced acute kidney injury by reducing the oxidative stress. Ir J Med Sci 185, 649–654 (2016). https://doi.org/10.1007/s11845-015-1328-z

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  • DOI: https://doi.org/10.1007/s11845-015-1328-z

Keywords

  • Renal
  • Ischemia
  • Reperfusion
  • Hydrogen sulfide