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


METHODS
Prospective, in vitro study.


METHODS
Experimental medical research laboratory at a University Hospital.


METHODS
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.


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.


CONCLUSIONS
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.
Delogu
Giovanna
G
Department of Anesthesia and Intensive Care, University Hospital, Policlinico Umberto 1, Rome, Italy. giovanna.delogu@uniroma1.it
Antonucci
Adriana
A
Moretti
Sonia
S
Marandola
Maurizio
M
Tellan
Guglielmo
G
Signore
Michele
M
Famularo
Giuseppe
G
D000777:Anesthetics / Q000097:blood / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000097:blood / Q000494:pharmacology; D002469:Cell Separation; D004305:Dose-Response Relationship, Drug; D004329:Droperidol / Q000097:blood / Q000494:pharmacology; D005978:Glutathione / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D006993:Hypnotics and Sedatives / Q000097:blood / Q000494:pharmacology; D066298:In Vitro Techniques; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009467:Neuromuscular Depolarizing Agents / Q000097:blood / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D015742:Propofol / Q000097:blood / Q000494:pharmacology; D011446:Prospective Studies; D017382:Reactive Oxygen Species / Q000032:analysis; D012016:Reference Values; D013390:Succinylcholine / Q000097:blood / Q000494:pharmacology; D013874:Thiopental / Q000097:blood / Q000494:pharmacology
D000777:Anesthetics; D014150:Antipsychotic Agents; D006993:Hypnotics and Sedatives; D009467:Neuromuscular Depolarizing Agents; D017382:Reactive Oxygen Species; D005978:Glutathione; D013390:Succinylcholine; D013874:Thiopental; D004329:Droperidol; D015742:Propofol