Background
Some of the postulated molecular mechanisms of sepsis progression are linked with
the imbalance between reactive oxygen species (ROS) production and its degradation
by cellular antioxidant pathways. Some studies have correlated plasma oxidative stress,
inflammatory markers, and clinical markers of organ failure, but none performed this
in a systematic way, determining in situ oxidative and inflammatory markers and correlating these with markers of organ failure.
Materials and Methods
Rats subjected to cecal ligation and puncture (CLP) were treated with basic support
or antioxidants and killed 12 h after to determine thiobarbituric acid reactive species
(as an index of oxidative damage), superoxide dismutase (SOD), catalase (CAT), and
myeloperoxidase (MPO) (as an index of neutrophil infiltration) in the kidney and lung.
In addition, protein content in bronchoalveolar lavage fluid (as an index of lung
alveolo-capillary dysfunction) and plasma urea (as an index of kidney injury) were
measured at the same time.
Results
In the CLP group, we found a positive correlation between thiobarbituric acid reactive
species (TBARS) and markers of organ injury in lung and kidney. Oxidative damage is
correlated with an increase in SOD/CAT ratio only in the lung. In contrast, oxidative
damage is correlated with MPO activity in the kidney, but not lung, suggesting different
sources of oxidative damage depending on the analyzed organ. These reflect differences
on the effects of basic support and antioxidants on organ dysfunction after sepsis.
Conclusion
Despite the general occurrence of oxidative damage in different organs during sepsis
development and a positive correlation between oxidative markers and organ injury,
antioxidant effects seemed to depend not only on the diminution of oxidative damage
but also on its anti-inflammatory activity.
Key Words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of Surgical ResearchAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care.Crit Care Med. 2001; 29: 1303
- Acute renal failure and sepsis.N Engl J Med. 2004; 351: 159
- The pathophysiology and treatment of sepsis.New Eng J Med. 2003; 348: 138
- Oxidative stress in septic shock and disseminated intravascular coagulation.Free Radic Biol Med. 2002; 33: 1173
- Protein carbonyl measurements show evidence of early oxidative stress in critically ill patients.Crit Care Med. 2000; 28: 143
- Inactivation of catecholamines by superoxide gives new insights on the pathogenesis of septic shock.Proc Natl Acad Sci USA. 2000; 97: 9753
- The role of free radicals in sepsis development.Front Biosci. 2009; 1: 277
- Oxidative variables in the rat brain after sepsis induced by cecal ligation and perforation.Crit Care Med. 2006; 34: 886
- Treatment with N-acetylcysteine plus deferoxamine protects rats against oxidative stress and improves survival in sepsis.Crit Care Med. 2004; 32: 342
- Oxidative parameters and mortality in sepsis induced by cecal ligation and perforation.Intensive Care Med. 2003; 29: 1782
- Oxidative parameters differences during non-lethal and lethal sepsis development.J Surg Res. 2005; 125: 68
- Sepsis and septic shock—a review of laboratory models and a proposal.J Surg Res. 1980; 29: 189
- et al Characterization of a hyperdynamic murine model of resuscitated sepsis using echocardiography.Am J Respir Crit Care Med. 2001; 164: 891
- Malondialdehyde determination as index of lipid peroxidation.Methods Enzymol. 1990; 186: 421
- Protein measurement with the Folin phenol reagent.J Biol Chem. 1951; 193: 265
- Catalase in vitro.Methods Enzymol. 1984; 105: 121
- Assays for superoxide dismutase.Methods Biochem Anal. 1987; 32: 279
- Assays of glutathione peroxidase.Methods Enzymol. 1984; 105: 114
- Edema and cell infiltration in the phorbol ester-treated mouse ear are temporally separate and can be differentially modulated by pharmacologic agents.Agents Actions. 1989; 26: 335
- Effects of N-acetylcysteine plus deferoxamine in lipopolysaccharide induced acute lung injury in the rat.Crit Care Med. 2006; 34: 471
- Animal models of sepsis: Setting the stage.Nat Rev Drug Discov. 2005; 4: 854
- Cecal ligation and puncture.Shock. 2005; 52
- Mechanism of sepsis-induced organ dysfunction.Crit Care Med. 2007; 35: 2408
- Antibiotic therapy reduces nitrosative stress and programmed cell death in the rabbit fetal lung.Eur Respir J. 2005; 25: 88
- Superoxide anion overproduction in sepsis: Effects of vitamin e and simvastatin.Shock. 2004; 22: 34
- Molecular characterization of a superoxide-generating NAD(P)H oxidase in the ventilatory muscles.Am J Respir Crit Care Med. 2002; 165: 412
- Xanthine oxidase activity in patients with sepsis.Clin Biochem. 2008; 41: 1186
- Free radical in biology and medicine.Oxford University Press, Oxford, UK1999
- Copper/zinc superoxide dismutase transgenic brain accumulates hydrogen peroxide after perinatal hypoxia ischemia.Ann Neurol. 1998; 44: 357
- Transfection with human copper-zinc superoxide dismutase induces bidirectional alterations in other antioxidant enzymes, proteins, growth factor response, and paraquat resistance.Free Radic Biol Med. 1995; 18: 497
- The cardioprotective effect of Mn-superoxide dismutase is lost at high doses in the postischemic isolated rabbit heart.Free Radic Biol Med. 1990; 9: 473
- Cardioprotection by CuZn-superoxide dismutase is lost at high doses in the reoxygenated heart.Free Radic Biol Med. 1990; 9: 465
- Immunopathologic alterations in murine models of sepsis of increasing severity.Infect Immun. 1999; 67: 6603
- Regulation of manganese superoxide dismutase by lipopolysaccharide, interleukin-1, and tumor necrosis factor. Role in the acute inflammatory response.J Biol Chem. 1990; 265: 2856
- Manganese superoxide dismutase: A hepatic acute phase protein regulated by interleukin-6 and glucocorticoids.Endocrinology. 1991; 129: 2376
- Superoxide radical inhibits catalase.J Biol Chem. 1982; 257: 5751
- Mitochondrial superoxide production is related to the control of cytokine release from peritoneal macrophage after antioxidant treatment in septic rats.J Surg Res. 2007; 141: 252
- Effect of sesame oil on oxidative-stress-associated renal injury in endotoxemic rats: Involvement of nitric oxide and proinflammatory cytokines.Shock. 2005; 24: 276
Article info
Publication history
Published online: September 10, 2009
Received:
June 25,
2009
Identification
Copyright
© 2011 Elsevier Inc. Published by Elsevier Inc. All rights reserved.