Role of Kupffer cells and PMN leukocytes in hepatic and systemic oxidativestress in rats subjected to tourniquet shock

Kupffer cells (KCs) have been implicated in leukocyte recruitment and micro vascular dysfunction associated with liver inflammation. The overall object ive of this study was to assess the role of KCs and polymorphonuclear (PMN) leukocytes on the oxidative stress elicited in the liver as a consequence of hind limb reperfusion in rats subjected to tourniquet shock, a shock mod el that differs from other models in that hepatic injury is a consequence o f remote organ damage. Colloidal carbon clearance from blood and its incorp oration into KCs demonstrate that these cells are activated after the 2 h h ind limb reperfusion period and that they are responsible for the observed oxidative stress and for PMN leukocyte recruitment and activation. Liver ox idative stress in this model is evidenced by increased liver tissue GSSG/GS H ratio, thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation, myeloperoxidase (MPO) activity, an index of tissue-associate d neutrophil accumulation, and a significant loss in total tissue superoxid e dismutase (SOD) activity. Mean arterial blood pressure (MAP), as well as plasma levels of alanine aminotransferase (ALT), an index of hepatic tissue injury, total SOD activity, plasma levels of or-tocopherol and p-carotene, and total plasma nitrite are also affected as a consequence of KC activati on after the 2 h hind limb reperfusion period. Inhibition of KC activity by gadolinium chloride (GdCl3) reverted most of the above alterations to valu es that do no differ from those found in control animals. These results sup port the hypothesis that hepatic and systemic oxidative stress elicited by hind limb reperfusion in rats subjected to tourniquet shock is both KC and PMN leukocyte dependent.