PON1 and oxidative stress in human sepsis and an animal model of sepsis

Dragomir Draganov, John Teiber, Catherine Watson, Charles Bisgaier, Jean Nemzek, Daniel Remick, Theodore Standiford, Bert La Du

Research output: Chapter in Book/Report/Conference proceedingChapter

33 Scopus citations

Abstract

Sepsis is the leading cause of death in critically ill patients. The pathophysiological mechanisms implicated in the development of sepsis and organ failure are complex and involve activation of systemic inflammatory response and coagulation together with endothelial dysfunction. Oxidative stress is a major promoter and mediator of the systemic inflammatory response. Serum PON1 has been demonstrated in multiple clinical and animal studies to protect against oxidative stress, but also to undergo inactivation upon that condition. We found decreased plasma PON1 activity in patients with sepsis compared to healthy controls or critically ill patients without sepsis; furthermore, in sepsis patients PON1 activity was lower and remained lower in the course of sepsis in the non-survivors compared to the survivors. Plasma PON1 activity was positively correlated with high-density lipoprotein cholesterol and negatively correlated with markers of lipid peroxidation. In an experimental animal model of sepsis, murine cecal ligation and puncture, the time course of plasma PON1 activity was very similar to that found in sepsis patients. Persistently low PON1 activity in plasma was associated with lethal outcome in human and murine sepsis.

Original languageEnglish (US)
Title of host publicationParaoxonases in Inflammation, Infection, and Toxicology
EditorsSrinivasa Reddy
Pages89-97
Number of pages9
DOIs
StatePublished - Dec 1 2010

Publication series

NameAdvances in Experimental Medicine and Biology
Volume660
ISSN (Print)0065-2598

Keywords

  • Cecal ligation and puncture model
  • Critically ill patients
  • High-density lipoprotein
  • Lipid peroxides
  • Oxidative stress
  • Sepsis
  • Systemic inflammatory response
  • Thiobarbituric acid reacting substances
  • Total antioxidant activity

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Draganov, D., Teiber, J., Watson, C., Bisgaier, C., Nemzek, J., Remick, D., Standiford, T., & Du, B. L. (2010). PON1 and oxidative stress in human sepsis and an animal model of sepsis. In S. Reddy (Ed.), Paraoxonases in Inflammation, Infection, and Toxicology (pp. 89-97). (Advances in Experimental Medicine and Biology; Vol. 660). https://doi.org/10.1007/978-1-60761-350-3_9