Arterial levels of oxidized glutathione (GSSG) reflect oxidant stress in vivo.
Neutrophil-related, oxidant-mediated injury to the pulmonary microvasculature appears to follow endotoxemia, cutaneous thermal injury, and ischemia-reperfusion injury to the liver or intestine. Glutathione is an important endogenous intracellular oxygen radical scavenger. Plasma concentrations of oxidized glutathione (GSSG) reflect oxidant injury resulting from an overdose of certain oxidatively metabolized drugs. The purpose of this investigation was to evaluate plasma GSSG as an indicator of oxidant stress resulting from activation of the endogenous inflammatory response. An established model of neutrophil- and oxidant-related acute lung injury following intestinal ischemia and reperfusion in rats was used. Intestinal ischemia was induced by clip occlusion of the superior mesenteric artery (SMA) for 120 min. Reperfusion resulted from SMA clip removal. Following reperfusion for 0, 15, or 120 min, plasma GSSG levels in portal vein, inferior vena cava (IVC), and aorta were obtained. Plasma GSSG was undetectable in sham animals and those with intestinal ischemia alone. Following reperfusion, all plasma samples had significant elevations in GSSG. Aortic plasma GSSG after 15 min of reperfusion was significantly elevated compared to both portal vein and IVC plasma GSSG. These data suggest that oxidant stress after intestinal reperfusion is reflected by elevations in plasma GSSG. The step up in plasma GSSG across the pulmonary vascular bed, a site of known oxidant injury, suggests that plasma GSSG may be a useful marker of oxidant stress in vivo, particularly with regard to the pulmonary microvasculature. This simple in vivo approach to assessing oxidant stress related to inflammatory tissue injury may have the potential to be of significant use in the clinical setting.
Abdalla
E K
EK
Department of Surgery, University of Michigan Medical School, Ann Arbor 48109.
Caty
M G
MG
Guice
K S
KS
Hinshaw
D B
DB
Oldham
K T
KT
D000818:Animals; D001158:Arteries; D005978:Glutathione / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D019803:Glutathione Disulfide; D007422:Intestines / Q000098:blood supply; D007511:Ischemia / Q000150:complications; D008168:Lung / Q000378:metabolism; D008297:Male; D010100:Oxygen; D011652:Pulmonary Circulation; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000150:complications; D013312:Stress, Physiological / Q000097:blood / Q000139:chemically induced*; D014652:Vascular Diseases / Q000209:etiology
D005978:Glutathione; D010100:Oxygen; D019803:Glutathione Disulfide