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Oxidative parameters and mortality in sepsis induced by cecal ligation and perforation

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Abstract

Objective

This study assessed parameters of free radical damage to biomolecules, mitochondrial superoxide production, superoxide dismutase, and catalase activities and their relationship to sepsis mortality.

Design and setting

Prospective animal study in a university laboratory for experimental.

Subjects

140 male Wistar rats.

Interventions

The animals were randomly divided into three groups: sham-operated (n=20), cecal ligation and perforation resuscitated with normal saline (n=40), and cecal ligation and perforation with normal saline plus antibiotics (n=40).

Measurements and results

Blood samples were collected from all animals 3, 12, and 24 h after CLP through a jugular catheter inserted before CLP. Rats were evaluated during 5 days after the intervention. Nonsurvivor animals were grouped according to the duration between sepsis induction and death, and oxidative parameters were compared to survivors and sham-operated. Lipid peroxidation, protein carbonyls, and superoxide dismutase were significantly increased in nonsurvivor septic rats and were predictive of mortality. We demonstrated that there is a different modulation of superoxide dismutase and catalase in nonsurvivors during the course of septic response. There was a marked increase in superoxide dismutase activity without a proportional increase in catalase activity in nonsurvivors.

Conclusions

This is the first report of plasma superoxide dismutase as an earlier marker of mortality. Ours results might help to clarify an important aspect of oxidative response to sepsis, i.e., an increase in superoxide dismutase activity without a proportional increase in catalase activity

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References

  1. Barriere SL, Lowry SF (1995) An overview of mortality risk prediction in sepsis. Crit Care Med 23:376–393

    CAS  PubMed  Google Scholar 

  2. Macarthur H, Westfall TC, Riley DP, Misko TP, Salvemini D (2000) Inactivation of catecholamines by superoxide gives new insights on the pathogenesis of septic shock. Proc Natl Acad Sci USA 97:9753–9758

    Article  CAS  PubMed  Google Scholar 

  3. Salvemini D, Cuzzocrea S (2002) Oxidative stress in septic shock and disseminated intravascular coagulation. Free Radic Biol Med 33:1173–1185

    Article  CAS  PubMed  Google Scholar 

  4. Zimmermann JJ (1995) Defining the role of oxyradicals in the pathogenesis of sepsis. Crit Care Med 23:616–617

    CAS  PubMed  Google Scholar 

  5. Chang CK, Llanes S, Schumer W (1999) Inhibiotry effect of DMSO on nuclear factor-κB activation and intracellular adhesion molecule 1 gene expression in septic rat. J Surg Res 82:294–299

    Article  CAS  PubMed  Google Scholar 

  6. Fujimura N, Sumita S, Aimono M (2000) Effect of free radical scavenger on diaphragmatic contractility in septic peritonitis. Am J Respir Crit Care Med 162:2159–2165

    CAS  PubMed  Google Scholar 

  7. Ortolani O, Conti A, Gaudio AR (2000) The effect of glutathione and N-acetylcysteine on lipoperoxidative damage in patients with early septic shock. Am J Respir Crit Care Med 161:1907–1911

    CAS  PubMed  Google Scholar 

  8. Heller AR, Groth G, Heller SC (2001) N-acetylcysteine reduces respiratory burst but augments neutrophil phagocytosis in intensive care unit patients. Crit Care Med 29:272–276

    CAS  PubMed  Google Scholar 

  9. Rank N, Michel C, Haertel C (2000) NAC increases liver blood flow and improves liver function in septic shock patients: results of a prospective, randomized, double-blind study. Crit Care Med 28:3799–3807

    PubMed  Google Scholar 

  10. Vulcano M, Meiss RP, Isturiz MA (2000) Deferoxamine reduces tissue injury and lethality in LPS-treated mice. Int J Immunopharmacol 22:635–644

    Google Scholar 

  11. Powell RJ, Machiedo GW, Rush BF Jr, Dikdan GS (1991) Effect of oxygen-free radical scavengers on survival in sepsis. Am Surg 57:86–88

    CAS  PubMed  Google Scholar 

  12. Kunimoto F, Morita T, Ogawa R, Fujita T (1987) Inhibition of lipid peroxidation improves survival rate of endotoxemic rats. Circ Shock 21:15–22

    CAS  PubMed  Google Scholar 

  13. Broner CW, Shenep JL, Stidham GL, Stokes DC, Hildner WK (1988) Effect of scavengers of oxygen-derived free radicals on mortality in endotoxin-challenged mice. Crit Care Med 16:848–851

    CAS  PubMed  Google Scholar 

  14. Kong CW, Tsai K, Chin JH, Chan WL, Hong CY (2000) Magnolol attenuates peroxidative damage and improves survival of rats with sepsis. Shock 13:24–28

    CAS  PubMed  Google Scholar 

  15. Warner BW, Hasselgren PO, James JH (1987) Superoxide dismutase in rats with sepsis. Effect on survival rate and amino acid transport. Arch Surg 122:1142–1146

    CAS  PubMed  Google Scholar 

  16. Broner CW, Shenep JL, Stidham GL (1989) Effect of antioxidants in experimental Escherichia coli septicemia. Circ Shock 29:77–92

    CAS  PubMed  Google Scholar 

  17. Sprong RC, Winkelhuyzen-Janssen AML, Aarsman CJM, van Oirschot JFLM, Bruggen T, van Asbeck BS (1998) Low-dose N-acetylcysteine protects rats against endotoxin-mediated oxidative stress, but high-dose increases mortality. Am J Respir Crit Care Med 157:1283–1293

    CAS  PubMed  Google Scholar 

  18. Wichterman KA, Baue AE, Chaudry IH (1980) Sepsis and septic shock–a review of laboratory models and a proposal. J Surg Res 29:189–199

    CAS  PubMed  Google Scholar 

  19. Hollenberg SM, Dumasius A, Easington C, Colilla SA, Neumann A, Parrillo JE (2001) Characterization of a hyperdynamic murine model of resuscitated sepsis using echocardiography. Am J Respir Crit Care Med 164:891–895

    CAS  PubMed  Google Scholar 

  20. Draper HH, Hadley M (1990) Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol 186:421–431

    CAS  PubMed  Google Scholar 

  21. Levine RL, Garland D, Oliver CN (1990) Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol 186:464–478

    CAS  PubMed  Google Scholar 

  22. Dal-Pizzol F, Klamt F, Bernard EA, Benfato MS, Moreira JCF (2001) Retinol supplementation induces oxidative stress and modulates antioxidant enzyme activities in rat Sertoli cells. Free Radic Res 34:395–404

    CAS  PubMed  Google Scholar 

  23. Bannister JV, Calaberese L (1987) Assays for SOD. Methods Biochem Anal 32:279–312

    CAS  PubMed  Google Scholar 

  24. Poderoso JJ, Carreras MC, Lisdero C, Boveris A (1996) Nitric oxide inhibits electron transfer and increases superoxide radical production in rat heart mitochondrial and submitochondrial particles. Arch Biochem Biophys 328:85–92

    Article  CAS  PubMed  Google Scholar 

  25. Lloyd SS, Chang AK, Taylor FB Jr (1993) Free radicals and septic shock in primates: the role of tumor necrosis factor. Free Radic Biol Med 14:233–242

    Article  CAS  PubMed  Google Scholar 

  26. Callahan LA, Nethery D, Stofan D, DiMarco A, Supinski G (2001) Free radical-induced contractile protein dysfunction in endotoxin-induced sepsis. Am J Respir Cell Mol Biol 24:210–217

    CAS  PubMed  Google Scholar 

  27. Basu S, Eriksson M (1998) Oxidative injury and survival during endotoxemia. FEBS Lett 438:159–160

    Article  CAS  PubMed  Google Scholar 

  28. Németh I, Boda D (2001) Xanthine oxidase activity and blood glutathione redox ratio in infants and children with septic shock syndrome. Intensive Care Med 27:216–221

    Google Scholar 

  29. Winterbourn CC, Buss IH, Chan TP (2000) Protein carbonyl measurements show evidence of early oxidative stress in critically ill patients. Crit Care Med 28:143–149

    CAS  PubMed  Google Scholar 

  30. McCord JM (1998) The importance of oxidant-antioxidant balance. In: Montagneir L, Olivier R, Pasquier C (eds) Oxidative stress in cancer, AIDS, and neurodegenerative diseases. Dekker, New York, pp 1–8

  31. Klamt F, Dal-Pizzol F, Frota Jr MLC, Andrades M, Silva EG, Walz R, Izquierdo I, Brentani RR, Moreira JCF (2001) Imbalance of antioxidant defences in mice lacking cellular prion protein. Free Radic Biol Med 30:1137–1144

    Article  CAS  PubMed  Google Scholar 

  32. Dal-Pizzol F, Klamt F, Andrades M, Frota Jr MLC, Caregnato F, Quevedo J, Schorder N, Vianna M, Izquierdo I, Archer T, Moreira JCF (2001) Neonatal iron administration induces oxidative stress in adult Wistar rats. Brain Res Dev Brain Res 130:109–114

    Article  CAS  PubMed  Google Scholar 

  33. Dal-Pizzol F, Ritter C, Klamt F, Andrades M, Frota Jr MLC, Diel C, da Rocha A, de Lima C, Braga Filho A, Schwartsmann G, Moreira JCF (2003) Modulation of oxidative stress in response to gamma-radiation in human glioma cell lines. J Neurooncol 61:89–94

    Article  PubMed  Google Scholar 

  34. Warner A, Bencosme A, Healy D, Verme C (1995) Prognostic role of antioxidant enzymes in sepsis: preliminary assessment. Clin Chem 41:867–871

    CAS  PubMed  Google Scholar 

  35. Bianca REV, Wayman NS, McDonald MC, Pinto A, Sharpe MA, Chatterjee PK, Thiemermann C (2002) Superoxide dismutase mimetic with catalase activity, EUK-134, attenuates the multiple organ injury and dysfunction caused by endotoxin in the rat. Med Sci Monit 8:BR1–BR7

    PubMed  Google Scholar 

  36. Salvemini D, Cuzzocrea S (2003) Therapeutical potential of superoxide dismutase mimetics as therapeutic agents in critical care medicine. Crit Care Med 31 [Suppl]:29–38

    Google Scholar 

  37. Traber DL, Adams T, Sziebvert L (1985) Potentiation of lung vascular response to endotoxin by superoxide dismutase. J Appl Physiol 58:1005–1009

    CAS  PubMed  Google Scholar 

  38. Olsen NC, Grizzle MK, Anderson DL (1987) Effect of polyethylene glycol-superoxide dismutase and catalase on endotoxemia in pigs. J Appl Physiol 63:1526–1532

    PubMed  Google Scholar 

  39. Novotny MJ, Laighlin MH, Adams H (1998) Evidence of lack of importance of oxygen free radicals in Escherichia coli endotoxemia in dogs. Am J Physiol 254:H954–H962

    Google Scholar 

  40. McKechnie K, Furman BL, Parrat JR (1986) Modification by oxygen free radical scavengers of the metabolic and cardiovascular effects of endotoxin infusion in conscious rats. Circ Shock 19:429–439

    CAS  PubMed  Google Scholar 

  41. Masuda A, Longo DL, Kobayashi Y (1988) Induction of mitochondrial manganese superoxide dismutase by interleukin 1. FASEB J 2:3087–3091

    CAS  PubMed  Google Scholar 

  42. Visner GA, Douglas WC, Wilson JM, Burr IA, Nick HS (1990) Regulation of manganese superoxide dismutase by lipopolysaccaride, interleukin-1, and tumor necrosis factor. J Biol Chem 265:2856–2864

    CAS  PubMed  Google Scholar 

  43. Gantchev TG, van Lier JE (1995) Catalase inactivation following photosensitization with tetrasulfonated metallophthalocyanines. Photochem Photobiol 62:123–134

    CAS  PubMed  Google Scholar 

  44. Boczkowski J, Lisdero CL, Lanone S, Boveris A, Poderoso JJ (1999) Endogenous peroxynitrite mediates mitochondrial dysfunction in rat diaphragm during endotoxemia. FASEB J 13:1637–1647

    CAS  PubMed  Google Scholar 

  45. Ritter C, Andrades M, Moreira JCF, Dal-Pizzol F (2003) Superoxide production during sepsis development. Am J Respir Crit Care Med 167:474–475

    PubMed  Google Scholar 

  46. Boveris A, Alvarez S, Navarro A (2002) The role of mitochondrial nitric oxide synthase in inflammation and septic shock. Free Radic Biol Med 33:1186–1193

    Article  CAS  PubMed  Google Scholar 

  47. Sanlioglu S, Williams CM, Samavati L (2001) LPS induces Rac-1-dependent reactive oxygen species formation and coordinates tumor necrosis factor-α secretion through IKK regulation of NF-κB. J Biol Chem 276:30188–30198

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from FAPERGS, FIPE-HCPA, and CNPq. The authors thank to Dr. R. Roesler for his critical revision of the manuscript.

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Correspondence to Felipe Dal-Pizzol.

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An editorial regarding this article can be found in the same issue (http://dx.doi.org/10.1007/s00134-003-1861-5)

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Ritter, C., Andrades, M., Frota, M.L.C. et al. Oxidative parameters and mortality in sepsis induced by cecal ligation and perforation. Intensive Care Med 29, 1782–1789 (2003). https://doi.org/10.1007/s00134-003-1789-9

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  • DOI: https://doi.org/10.1007/s00134-003-1789-9

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