Does neutrophil-mediated oxidative stress play any significant role in producing hepatocellular dysfunction during early sepsis?

Academic Article

Abstract

  • Background. Although previous studies have indicated that hepatocellular dysfunction during early sepsis can be prevented by prior neutrophil depletion, it remains unknown whether the changes in hepatic oxidative stress induced by activated neutrophils are responsible for the salutary effect of neutropenia on hepatocellular function. Materials and methods. Neutropenia was induced in the rat by intravenous injection of immunoglobulins directly against rat neutrophils (anti-neutrophil Ig) at 16 and 2 h prior to the initiation of cecal ligation and puncture (CLP, i.e., an animal model of polymicrobial sepsis) or sham operation. Neutropenia was confirmed by peripheral blood smears. Neutrophil-competent control animals were given nonimmunized Ig prior to the onset of sepsis. Sham animals received antineutrophil Ig or control Ig. The levels of reduced glutathione (GSH) and oxidized glutathione (GSSG) in the liver were determined at 5 h after CLP (i.e., the early, hyperdynamic stage of sepsis) or sham operation by high performance liquid chromatography. Results. Although the levels of hepatic GSH and GSSG decreased significantly at 5 h after CLP, irrespective of neutropenia, the ratio of GSSG/GSH was not significantly altered under such conditions. The decrease in hepatic glutathione concentrations in septic animals may represent the decreased synthesis or increased efflux into the bile or circulation. Conclusion. Since neutrophil depletion did not significantly affect hepatic levels of GSH and GSSG as well as the GSSG/GSH ratio but prevented the occurrence of hepatocellular dysfunction, factors other than oxidative stress are likely to be the mechanism responsible for depressing hepatocellular function during the early, hyperdynamic stage of sepsis.
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    Author List

  • Molnar RG; Wang P; Chaudry IH
  • Start Page

  • 75
  • End Page

  • 79
  • Volume

  • 80
  • Issue

  • 1