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 degrees C with the following drug concentrations: thiopental sodium 20 mmoL/mL, droperidol 130 micromol/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.
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 degrees C with the following drug concentrations: thiopental sodium 20 mmoL/mL, droperidol 130 micromol/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.
Authors: Hiroe Shiratsuchi; Yasser Kouatli; Guang Xiang Yu; Harold M Marsh; Marc D Basson Journal: Am J Physiol Cell Physiol Date: 2009-04-08 Impact factor: 4.249