PLASMA-LEVELS OF GLUTATHIONE, ALPHA-TOCOPHEROL AND LIPID PEROXIDES INPOLYTRAUMATIZED PATIENTS - EVIDENCE FOR A STIMULATING EFFECT OF TNF-ALPHA ON GLUTATHIONE SYNTHESIS

Prognosis and outcome of polytraumatized patients are determined by th e possible development of multiple organ failure (MOF). Among the dire ct traumatic organ damage, it is caused by a systemic inflammatory rea ction. This might be triggered by an activation of the inflammatory me diator cascade following hemorrhagic-traumatic shock as well as by oxy gen-derived free radicals (ROS). The aim of our present study was to a nswer the following questions: 1. Is the ''oxidative stress'' measurab le during the development of MOF after polytraumatic injury? 2, Is the re a relation between the activation of the inflammatory mediator casc ade and changes of the organism's antioxidative system? The study grou p included 26 patients (15 survivors, 11 non-survivors) suffering from severe polytraumatic injury (Hannover Polytrauma Score 12-63 points). Plasma levels of reduced (GSH) and oxidized (GSSG) glutathione alpha- tocopherol (TOC), lipid peroxides (expressed in terms of thiobarbituri c acid reagible substances = TEARS), and tumor necrosis factor alpha ( TNF) were measured each day from the point of admission on the ICU unt il the discharge or death of the patients. The following results were obtained: Independent from the outcome, we observed a continuous loss of plasma sulfhydryl groups and TOC. In the patients developing a MOF score > 5 on 10th day after injury (n = 6), a significant increase in plasma GSSG level was measurable. Additionally, a total loss of plasma GSH was seen in some of these patients indicating the collapse of the GSH-dependent antioxidative system. Similar changes were never observ ed in patients with MOF score less than or equal to 5 on 10th day afte r injury (n = 15). In this group, a significant correlation between pl asma TNF peaks and short time GSH boosts was obtained as a possible in dicative for a stimulating effect of TNF on GSH synthesis. It can be c oncluded that processes of oxidative stress in connection with a consu mption of endogenic antioxidants might be able to promote the developm ent of MOF after polytraumatic injury.