Oxidative stress and mitochondrial glutathione in human lymphocytes exposed to clinically relevant anesthetic drug concentrations

Study objective To evaluate the potential of compounds commonly used in anesthesia practice to affect the intracellular oxidant-antioxidant homeostasis of peripheral blood lymphocytes at clinically relevant concentrations; and to study the changes in reactive oxygen species production and measure the mitochondrial glutathione content. Design Prospective, in vitro study. Setting Experimental medical research laboratory at a University Hospital. Measurements Lymphocytes were isolated from the peripheral blood of 15 healthy donors and incubated for 12 hours at 37°C with the following drug concentrations: thiopental sodium 20 mmoL/mL, droperidol 130 μmol/mL, propofol 60 mmoL/mL, and succinylcholine 17 mmoL/mL. Reactive oxygen species (ROS) generation was determined by hydroethidine and 2′,7′-dichlorofluorescein diacetate methods. Mitochondrial glutathione level was assessed using monobromobimane staining. Measurements and main results Thiopental-treated lymphocytes exhibited an overgeneration of ROS, but no change was detected in mitochondrial glutathione quantity. Propofol and droperidol could not induce any perturbative effect on the oxidative state of T cells, whereas succinylcholine was found to markedly affect lymphocyte oxidative state both by impairing glutathione content and promoting exaggerated production of ROS. Conclusion Drugs commonly used in anesthesia practice may significantly alter the oxidative state of peripheral T cells. This mechanism could contribute to the immune suppression that occurs transiently in the early postoperative period. © 2004 by Elsevier Inc.