Plasma levels of glutathione, alpha-tocopherol and lipid peroxides in polytraumatized patients; evidence for a stimulating effect of TNF alpha on glutathione synthesis
Kretzschmar, M.; Pfeiffer, L.; Schmidt, C.; Schirrmeister, W.
Experimental and Toxicologic Pathology Official Journal of the Gesellschaft für Toxikologische Pathologie 50(4-6): 477-483
ISSN/ISBN: 0940-2993 PMID: 9784026 DOI: 10.1016/s0940-2993(98)80037-7
Prognosis and outcome of polytraumatized patients are determined by the possible development of multiple organ failure (MOF). Among the direct traumatic organ damage, it is caused by a systemic inflammatory reaction. This might be triggered by an activation of the inflammatory mediator cascade following hemorrhagic-traumatic shock as well as by oxygen-derived free radicals (ROS). The aim of our present study was to answer the following questions: 1. Is the "oxidative stress" measurable during the development of MOF after polytraumatic injury? 2. Is there a relation between the activation of the inflammatory mediator cascade and changes of the organism's antioxidative system? The study group 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 thiobarbituric acid reagible substances = TBARS), and tumor necrosis factor alpha (TNF) were measured each day from the point of admission on the ICU until 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 observed in patients with MOF score < or = 5 on 10th day after injury (n = 15). In this group, a significant correlation between plasma TNF peaks and short time GSH boosts was obtained as a possible indicative for a stimulating effect of TNF on GSH synthesis. It can be concluded that processes of oxidative stress in connection with a consumption of endogenic antioxidants might be able to promote the development of MOF after polytraumatic injury.