The Pathophysiological Significance of Reactive Oxygen Formation in Rat Liver

Abstract

Reactive oxygen species (ROS) are thought to be involved in the pathogenesis of various important human diseases and their therapeutic interventions, e.g. ischemia/reperfusion injuries such as myocardial infarction, stroke, shock and organ transplantation (McCord, 1985). Evidence for the involvement of ROS is mainly based on pharmacological interventions. Since in most cases several potential damaging mechanisms could contribute to cell and organ injury, the exact role of ROS remains unknown. We recently have been studying the quantification of intracellular ROS formation in various models of no-flow ischemia (Jaeschke et al., 1988) and hypoxia (Jaeschke et al., 1988; Jaeschke and Mitchell, 1989; Jaeschke, 1990a) in the liver by measurement of the biliary and sinusoidal release of glutathione disulfide (GSSG). It was found that during hypoxia even the physiological formation of ROS was suppressed by more than 80% (Jaeschke, 1990a). During reoxygenation ROS formation was estimated as 0.15 μmol O₂-/min/g liver wt., a 3–4 fold increase above physiological values (Jaeschke et al., 1988; Jaeschke and Mitchell, 1989). Formation of ROS caused by reperfusion after hepatic no-flow ischemia was estimated by these methods to be less than 0.05 μmol O₂-/min/g (Jaeschke et al., 1988).