Skip to main content
SpringerLink
Log in

Favorable balance of anti-oxidant/pro-oxidant systems and ablated oxidative stress in Brown Norway rats in renal ischemia-reperfusion injury

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Oxidative stress is important in the pathogenesis of renal ischemia-reperfusion (IR) injury; however whether imbalances in reactive oxygen production and disposal account for susceptibility to injury is unclear. The purpose of this study was to compare necrosis, apoptosis, and oxidative stress in IR-resistant Brown Norway rats vs. IR-susceptible Sprague-Dawley (SD) rats in an in vivo model of renal IR injury. As superoxide (O ·−2 ) interacts with nitric oxide (NO) to form peroxynitrite, inducible NO synthase (iNOS) and nitrotyrosine were also examined. Renal IR was induced in SD and BN rats by bilateral clamping of renal arteries for 45 min followed by reperfusion for 24 h (SD 24 and BN 24, respectively). BN rats were resistant to renal IR injury as evidenced by lower plasma creatinine and decreased acute tubular necrosis. TUNEL staining analysis demonstrated significantly decreased apoptosis in the BN rats vs. SD rats after IR. Following IR, O ·−2 levels were also significantly lower in renal tissue of BN rats vs. SD rats (P < 0.05) in conjunction with a preservation of the O ·−2 dismutating protein, CuZn superoxide dismutase (CuZn SOD) (P < 0.05). This was accompanied by an overall decrease in 4-hydroxynonenal adducts in the BN but not SD rats after IR. BN rats also displayed lower iNOS expression (P < 0.05) resulting in lower tissue NO levels and decreased nitrotyrosine formation (P < 0.01) following IR. Collectively these results show that the resistance of the BN rat to renal IR injury is associated with a favorable balance of oxidant production vs. oxidant removal.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. Edelstein CL, Ling H, Schrier RW (1997) The nature of renal cell injury. Kidney Int 51:1341–1351

    Article  PubMed  CAS  Google Scholar 

  2. Lameire N (2005) The pathophysiology of acute renal failure. Crit Care Clin 21:197–210

    Article  PubMed  Google Scholar 

  3. Lameire N, Van Biesen W, Vanholder R (2005) Acute renal failure. Lancet 365:417–430

    PubMed  CAS  Google Scholar 

  4. Chien CT, Lee PH, Chen CF et al (2001) De novo demonstration and co-localization of free-radical production and apoptosis formation in rat kidney subjected to ischemia/reperfusion. J Am Soc Nephrol 12:973–982

    PubMed  CAS  Google Scholar 

  5. McCord JM, Roy RS (1982) The pathophysiology of superoxide: roles in inflammation and ischemia. Can J Physiol Pharmacol 60:1346–1352

    PubMed  CAS  Google Scholar 

  6. McCord JM, Roy RS, Schaffer SW (1985) Free radicals and myocardial ischemia. The role of xanthine oxidase. Adv Myocardiol 5:183–189

    PubMed  CAS  Google Scholar 

  7. Unal D, Yeni E, Erel O et al (2002) Antioxidative effects of exogenous nitric oxide versus antioxidant vitamins on renal ischemia reperfusion injury. Urol Res 30:190–194

    Article  PubMed  CAS  Google Scholar 

  8. Wink DA, Hanbauer I, Krishna MC et al (1993) Nitric oxide protects against cellular damage and cytotoxicity from reactive oxygen species. Proc Natl Acad Sci USA 90:9813–9817

    Article  PubMed  CAS  Google Scholar 

  9. Wink DA, Miranda KM, Espey MG et al (2001) Mechanisms of the antioxidant effects of nitric oxide. Antioxid Redox Signal 3:203–213

    Article  PubMed  CAS  Google Scholar 

  10. Martinez-Mier G, Toledo-Pereyra LH, Bussell S et al (2000) Nitric oxide diminishes apoptosis and p53 gene expression after renal ischemia and reperfusion injury. Transplantation 70:1431–1437

    Article  PubMed  CAS  Google Scholar 

  11. Chatterjee PK, Patel NS, Kvale EO et al (2002) Inhibition of inducible nitric oxide synthase reduces renal ischemia/reperfusion injury. Kidney Int 61:862–871

    Article  PubMed  CAS  Google Scholar 

  12. Zahmatkesh M, Kadkhodaee M, Arab HA et al (2006) Effects of co-administration of an iNOS inhibitor with a broad-spectrum reactive species scavenger in rat renal ischemia/reperfusion injury. Nephron Exp Nephrol 103:e119–e125

    Article  PubMed  CAS  Google Scholar 

  13. Beckman JS (2002) Protein tyrosine nitration and peroxynitrite. FASEB J 16:1144

    Article  PubMed  Google Scholar 

  14. Beckman JS, Chen J, Ischiropoulos H et al (1994) Oxidative chemistry of peroxynitrite. Methods Enzymol 233:229–240

    PubMed  CAS  Google Scholar 

  15. Beckman JS, Ischiropoulos H, Zhu L et al (1992) Kinetics of superoxide dismutase- and iron-catalyzed nitration of phenolics by peroxynitrite. Arch Biochem Biophys 298:438–445

    Article  PubMed  CAS  Google Scholar 

  16. Goligorsky MS, Brodsky SV, Noiri E (2002) Nitric oxide in acute renal failure: NOS versus NOS. Kidney Int 61:855–861

    Article  PubMed  CAS  Google Scholar 

  17. Gow AJ, Ischiropoulos H (2001) Nitric oxide chemistry and cellular signaling. J Cell Physiol 187:277–282

    Article  PubMed  CAS  Google Scholar 

  18. Davies SJ, Reichardt-Pascal SY, Vaughan D et al (1995) Differential effect of ischaemia-reperfusion injury on anti-oxidant enzyme activity in the rat kidney. Exp Nephrol 3:348–354

    PubMed  CAS  Google Scholar 

  19. Jassem W, Fuggle SV, Rela M et al (2002) The role of mitochondria in ischemia/reperfusion injury. Transplantation 73:493–499

    Article  PubMed  CAS  Google Scholar 

  20. Dobashi K, Ghosh B, Orak JK et al (2000) Kidney ischemia-reperfusion: modulation of antioxidant defenses. Mol Cell Biochem 205:1–11

    Article  PubMed  CAS  Google Scholar 

  21. Cruthirds DL, Novak L, Akhi KM et al (2003) Mitochondrial targets of oxidative stress during renal ischemia/reperfusion. Arch Biochem Biophys 412:27–33

    Article  PubMed  CAS  Google Scholar 

  22. Cruthirds DL, Saba H, MacMillan-Crow LA (2005) Overexpression of manganese superoxide dismutase protects against ATP depletion-mediated cell death of proximal tubule cells. Arch Biochem Biophys 437:96–105

    Article  PubMed  CAS  Google Scholar 

  23. Yin M, Wheeler MD, Connor HD et al (2001) Cu/Zn-superoxide dismutase gene attenuates ischemia-reperfusion injury in the rat kidney. J Am Soc Nephrol 12:2691–2700

    PubMed  CAS  Google Scholar 

  24. Baker JE, Konorev EA, Gross GJ et al (2000) Resistance to myocardial ischemia in five rat strains: is there a genetic component of cardioprotection?. Am J Physiol Heart Circ Physiol 278:H1395–1400

    PubMed  CAS  Google Scholar 

  25. Basile DP, Donohoe D, Cao X et al (2004) Resistance to ischemic acute renal failure in the Brown Norway rat: a new model to study cytoprotection. Kidney Int 65:2201–2211

    Article  PubMed  CAS  Google Scholar 

  26. Shi Y, Hutchins W, Ogawa H et al (2005) Increased resistance to myocardial ischemia in the Brown Norway vs. Dahl S rat: role of nitric oxide synthase and Hsp90. J Mol Cell Cardiol 38:625–635

    Article  PubMed  CAS  Google Scholar 

  27. Blydt-Hansen TD, Katori M, Lassman C et al (2003) Gene transfer-induced local heme oxygenase-1 overexpression protects rat kidney transplants from ischemia/reperfusion injury. J Am Soc Nephrol 14:745–754

    Article  PubMed  CAS  Google Scholar 

  28. Pieper GM, Nilakantan V, Zhou X et al (2005) Treatment with {alpha}-phenyl-N-tert-butylnitrone, a free radical-trapping agent, abrogates inflammatory cytokine gene expression during alloimmune activation in rat cardiac allografts. J Pharmacol Exp Ther 312:774–779

    Article  PubMed  CAS  Google Scholar 

  29. Khadour FH, Panas D, Ferdinandy P (2002) Enhanced NO and superoxide generation in dysfunctional hearts from endotoxemic rats. Am J Physiol Heart Circ Physiol 283:H1108–H1115

    PubMed  CAS  Google Scholar 

  30. Nilakantan V, Zhou X, Hilton G et al (2005) Hierarchical change in antioxidant enzyme gene expression and activity in acute cardiac rejection: role of inducible nitric oxide synthase. Mol Cell Biochem 270:39–47

    Article  PubMed  CAS  Google Scholar 

  31. Nilakantan V, Halligan NL, Nguyen TK et al (2005) Post-translational modification of manganese superoxide dismutase in acutely rejecting cardiac transplants: role of inducible nitric oxide synthase. J Heart Lung Transplant 24:1591–1599

    Article  PubMed  Google Scholar 

  32. Wang Q, Tompkins KD, Simonyi A et al (2006) Apocynin protects against global cerebral ischemia-reperfusion-induced oxidative stress and injury in the gerbil hippocampus. Brain Res 1090:182–189

    Article  PubMed  CAS  Google Scholar 

  33. Dodd OJ, Pearse DB (2000) Effect of the NADPH oxidase inhibitor apocynin on ischemia-reperfusion lung injury. Am J Physiol Heart Circ Physiol 279:H303–H312

    Google Scholar 

  34. Rhoden E, Teloken C, Lucas M et al (2000) Protective effect of allopurinol in the renal ischemia-reperfusion in uninephrectomized rats. Gen Pharmacol 35:189–193

    PubMed  CAS  Google Scholar 

  35. Taylor NE, Glocka P, Liang M et al (2006) NADPH oxidase in the renal medulla causes oxidative stress and contributes to salt-sensitive hypertension in Dahl S rats. Hypertension 47:692–698

    Article  PubMed  CAS  Google Scholar 

  36. Afonso V, Santos G, Collin P et al (2006) Tumor necrosis factor-alpha down-regulates human Cu/Zn superoxide dismutase 1 promoter via JNK/AP-1 signaling pathway. Free Radic Biol Med 41:709–721

    Article  PubMed  CAS  Google Scholar 

  37. Eschwege P, Paradis V, Conti M et al (1999) In situ detection of lipid peroxidation by-products as markers of renal ischemia injuries in rat kidneys. J Urol 162:553–557

    Article  PubMed  CAS  Google Scholar 

  38. Walker LM, York JL, Imam SZ et al (2001) Oxidative stress and reactive nitrogen species generation during renal ischemia. Toxicol Sci 63:143–148

    Article  PubMed  CAS  Google Scholar 

  39. Erdogan H, Fadillioglu E, Yagmurca M et al (2006) Protein oxidation and lipid peroxidation after renal ischemia-reperfusion injury: protective effects of erdosteine and N-acetylcysteine. Urol Res 34:41–46

    Article  PubMed  CAS  Google Scholar 

  40. Noiri E, Nakao A, Uchida K et al (2001) Oxidative and nitrosative stress in acute renal ischemia. Am J Physiol Renal Physiol 281:F948–F957

    PubMed  CAS  Google Scholar 

  41. Yu L, Gengaro PE, Niederberger M et al (1994) Nitric oxide: a mediator in rat tubular hypoxia/reoxygenation injury. Proc Natl Acad Sci USA 91:1691–1695

    Article  PubMed  CAS  Google Scholar 

  42. Noiri E, Peresleni T, Miller F et al (1996) In vivo targeting of inducible NO synthase with oligodeoxynucleotides protects rat kidney against ischemia. J Clin Invest 97:2377–2383

    Article  PubMed  CAS  Google Scholar 

  43. Peresleni T, Noiri E, Bahou WF et al (1996) Antisense oligodeoxynucleotides to inducible NO synthase rescue epithelial cells from oxidative stress injury. Am J Physiol Renal Physiol 270:F971–F977

    CAS  Google Scholar 

  44. Ling H, Edelstein C, Gengaro P et al (1999) Attenuation of renal ischemia-reperfusion injury in inducible nitric oxide synthase knockout mice. Am J Physiol Renal Physiol 277:F383–F390

    CAS  Google Scholar 

  45. Ling H, Gengaro PE, Edelstein CL (1998) Effect of hypoxia on proximal tubules isolated from nitric oxide synthase knockout mice. Kidney Int 53:1642–1646

    Article  PubMed  CAS  Google Scholar 

  46. Chander V, Chopra K (2006) Possible role of nitric oxide in the protective effect of resveratrol in 5/6th nephrectomized rats. J Surg Res 133:129–135

    Article  PubMed  CAS  Google Scholar 

  47. Chander V, Chopra K (2006) Renal protective effect of molsidomine and L-arginine in ischemia-reperfusion induced injury in rats. J Surg Res 128:132–139

    Google Scholar 

  48. Mark LA, Robinson AV, Schulak JA (2005) Inhibition of nitric oxide synthase reduces renal ischemia/reperfusion injury. J Surg Res 129:236–241

    Article  PubMed  CAS  Google Scholar 

  49. Yamakura F, Matsumoto T, Fujimura T et al (2001) Modification of a single tryptophan residue in human Cu,Zn-superoxide dismutase by peroxynitrite in the presence of bicarbonate. Biochim Biophys Acta 1548:38–46

    PubMed  CAS  Google Scholar 

  50. Yamakura F, Matsumoto T, Ikeda K et al (2005) Nitrated and oxidized products of a single tryptophan residue in human Cu,Zn-superoxide dismutase treated with either peroxynitrite-carbon dioxide or myeloperoxidase-hydrogen peroxide-nitrite. J Biochem (Tokyo) 138:57–69

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Transplant Surgery, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI, 53226, USA

    Vani Nilakantan, Gail Hilton, Cheryl Maenpaa, Galen M. Pieper, Christopher P. Johnson & Brian D. Shames

  2. Kidney Disease Center, Medical College of Wisconsin, Milwaukee, WI, USA

    Vani Nilakantan, Scott K. Van Why & Brian D. Shames

  3. Division of Pediatric Nephrology, Medical College of Wisconsin, Milwaukee, WI, USA

    Scott K. Van Why

  4. Free Radical Research Center, Medical College of Wisconsin, Milwaukee, WI, USA

    Galen M. Pieper

  5. Clement J. Zablocki VA Medical Center, Medical College of Wisconsin, Milwaukee, WI, USA

    Christopher P. Johnson

Authors
  1. Vani Nilakantan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gail Hilton
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cheryl Maenpaa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Scott K. Van Why
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Galen M. Pieper
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Christopher P. Johnson
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Brian D. Shames
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vani Nilakantan.

Additional information

This work was supported in part by a Medical College of Wisconsin-Research Affairs Committee Grant to V. Nilakantan, and by divisional funds to V. Nilakantan and B.D. Shames.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nilakantan, V., Hilton, G., Maenpaa, C. et al. Favorable balance of anti-oxidant/pro-oxidant systems and ablated oxidative stress in Brown Norway rats in renal ischemia-reperfusion injury. Mol Cell Biochem 304, 1–11 (2007). https://doi.org/10.1007/s11010-007-9480-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-007-9480-z

Keywords

Search

Navigation