Circulating and muscle glutathione turnover in human endotoxemia

U. B. Fläring (1) , Christian Hebert , J. Wernerman , F. Hammarqvist , O. E. Rooyackers

1 Department of Anaesthesia and Intensive Care

Objective: Patients with septic shock have high plasma glutathione concentration, while intracellular concentrations in erythrocytes and muscle are low. Here we investigated the temporal pattern of glutathione status and glutathione kinetics in healthy volunteers during the initial phase of sepsis using a human endotoxin model. Design and setting: Descriptive pilot study in healthy male volunteers (n = 8) before and after an endotoxin challenge. Measurements and results: The glutathione status was determined in plasma and whole blood at baseline and hourly for 4 hours after intravenous endotoxin injection and in skeletal muscle at baseline and at 2 and 4 hours after endotoxin injection. In plasma the concentration of total glutathione decreased by 24 % (p < 0.05) at 3 hours after endotoxin injection and by 32 % (p < 0.001) at 4 hours. In whole blood and skeletal muscle, the concentrations of both reduced and total glutathione as well as the redox status remained unaltered during the initial 4 hours after an endotoxin challenge. The fractional synthesis rate (FSR) of glutathione in whole blood was 38±20 (%/day) before and 59±22 %/day 4 after the endotoxin challenge (p = 0.088) and in skeletal muscle 41±25 and 46±18 %/day (p=0.68) respectively. Conclusions: During the initial phase of sepsis as represented by an intravenous endotoxin challenge to healthy volunteers, plasma concentration of total glutathione decreased, while glutathione status and synthesis rate in skeletal muscle and whole blood remained unaltered. However, due to the variation in the synthesis measures, larger studies are needed to confirm these findings.

Mots clés: Medicine

U. B. Fläring, Christian Hebert, J. Wernerman, F. Hammarqvist, O. E. Rooyackers. Circulating and muscle glutathione turnover in human endotoxemia. Clinical Science, 2009, 117 (9), pp.313-319. ⟨10.1042/CS20080462⟩. ⟨hal-00512872⟩