DOES NEUTROPHIL-MEDIATED OXIDATIVE STRESS PLAY ANY SIGNIFICANT ROLE IN PRODUCING HEPATOCELLULAR DYSFUNCTION DURING EARLY SEPSIS

Background Although previous studies have indicated that hepatocellula r dysfunction during early sepsis can be prevented by prior neutrophil depletion, it remains unknown whether the changes in hepatic oxidativ e stress induced by activated neutrophils are responsible for the salu tary effect of neutropenia on hepatocellular function. Materials and m ethods. 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-com petent control animals were given nonimmunized Ig prior to the onset o f sepsis. Sham animals received antineutrophil Ig or control Ig. The l evels of reduced glutathione (GSH) and oxidized glutathione (GSSG) in the liver were determined at 5 h after CLP (i.e., the early, hyperdyna mic stage of sepsis) or sham operation by high performance liquid chro matography. Results. Although the levels of hepatic GSH and GSSG decre ased 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 bil e or circulation. Conclusion. Since neutrophil depletion did not signi ficantly affect hepatic levels of GSH and GSSG as well as the GSSG/GSH ratio but prevented the occurrence of hepatocellular dysfunction, fac tors other than oxidative stress are likely to be the mechanism respon sible for depressing hepatocellular function during the early, hyperdy namic stage of sepsis. (C) 1998 Academic Press.