Extracellular superoxide dismutase attenuates lung injury after hemorrhage.
Reperfusion of the lung after hemorrhage generates free radicals such as superoxide (O(2)(.)) that may injure the lung; however, the relative importance of intracellular versus extracellular free radicals is unclear. The superoxide dismutases (SOD) are the primary enzymatic method to reduce superoxide. We examined whether lung-specific overexpression of extracellular superoxide dismutase (EC-SOD) would attenuate hemorrhage-induced lung injury. Wild-type mice and mice overexpressing the human EC-SOD gene with a lung-specific promoter were hemorrhaged by removing 30% of blood volume. After hemorrhage, the lung wet to dry weight ratios increased from 5.4 +/- 0.11 in unmanipulated control mice to 6.3 +/- 0.16 in wild-type mice, but to only 5.60 +/- 0.17 in the EC-SOD transgenic mice (p < 0.05 compared with hemorrhaged wild-type). Hemorrhage-induced lipid peroxidation, as assessed by lung F(2) isoprostanes, was lower in the EC-SOD transgenic mice (3.4 +/- 0.3 microg/lung) compared with wild-type mice (1.9 +/- 0.2 microg/lung; p < 0.05). Compared with wild-type, EC-SOD transgenic mice had attenuated the hemorrhage-induced increase in both pulmonary nuclear factor kappa B (NK-kappaB) activation (relative absorbance 1.1 +/- 0.2 for EC-SOD transgenic versus 2.5 +/- 0.1 for wild-type; p < 0.05) and myeloperoxidase activity (5.1 +/- 0.87 units/g for EC-SOD transgenic versus 11.3 +/- 1.8 units/g for wild-type; p < 0.01). Thus, overexpression of pulmonary EC-SOD in the mouse lung attenuates lung injury after hemorrhage.
Bowler
R P
RP
National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206, USA. BowlerR@njc.org
Arcaroli
J
J
Crapo
J D
JD
Ross
A
A
Slot
J W
JW
Abraham
E
E
D000818:Animals; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D006470:Hemorrhage / Q000150:complications*; D008171:Lung Diseases / Q000188:drug therapy* / Q000209:etiology; D051379:Mice; D013482:Superoxide Dismutase / Q000627:therapeutic use*
D016166:Free Radical Scavengers; D013482:Superoxide Dismutase