Skip to main content

Effect of increasing endotoxin doses on oxidative injury and cyclooxygenase-mediated inflammation in the anaesthetised pig

Introduction

In this study the effect of the endotoxin dose on production of an F2-isoprostane, 8-iso-PGF, a free radical-mediated lipid peroxidation product, and 15-keto-dihydro-PGF, a major metabolite of PGF and cyclooxygenase (COX)-mediated inflammatory response, was investigated. Oxidative injury and COX-mediated inflammation play a central role in the manifestation of endotoxaemic shock. These eicosanoids are therefore markers of key processes in the pathophysiology of endotoxaemic shock. However, their relationship to the endotoxin dose has not been established.

Methods

Twenty pigs were anesthetised and given endotoxin at logarithmically increasing doses (0.063–16 μg/kg/hour). Three nonendotoxaemic pigs served as controls. 8-Iso-PGF and 15-keto-dihydro-PGF were measured in plasma at baseline and hourly for 6 hours. The dose–response to increasing doses of endotoxin was determined using the two-sided Jonckheere–Terpstra test.

Results

Endotoxin induced the formation of both 8-iso-PGF and 15-keto-dihydro-PGF. Increases in the endotoxin dose induced significant log-linear responses in 8-iso-PGF and 15-keto-dihydro-PGF (P < 0.001, P < 0.05, respectively) as depicted in Figure 1.

Figure 1
figure1

Relative changes in 8-iso-PGF and 15-keto-DH-PGF (values are mean ± SEM).

Conclusion

Our findings indicate that free radical-mediated lipid peroxidation and COX-mediated inflammatory response are dependent on the endotoxin dose in a log-linear fashion in this model.

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Lipcsey, M., Söderberg, E., Basu, B. et al. Effect of increasing endotoxin doses on oxidative injury and cyclooxygenase-mediated inflammation in the anaesthetised pig. Crit Care 12, P391 (2008). https://doi.org/10.1186/cc6612

Download citation

Keywords

  • Public Health
  • Lipid
  • Lipid Peroxidation
  • Inflammatory Response
  • Emergency Medicine