Transgenic mice with increased copper/zinc-superoxide dismutase activity are resistant to hepatic leukostasis and capillary no-reflow after gut ischemia/reperfusion.
The objectives of this study were to (1) determine whether transgenic (Tg) mice overexpressing copper/zinc-superoxide dismutase (CuZn-SOD) are protected from the deleterious effects of gut ischemia/reperfusion (I/R) and (2) compare the effectiveness of Tg SOD overexpression in attenuating I/R injury to intravascularly administered CuZn-SOD or manganese (Mn)-SOD. The accumulation of fluorescently labeled leukocytes and number of nonperfused sinusoids were monitored by intravital microscopy in livers of wild-type mice (C57BL/6), CuZn-SOD Tg mice, and wild-type mice receiving either CuZn-SOD or Mn-SOD. All parameters were measured for 1 hour after release of the occluded (for 15 minutes) superior mesenteric artery. Gut I/R in wild-type mice led to an increased number of stationary leukocytes, while reducing the number of perfused sinusoids (capillary no-reflow). All of these responses were significantly blunted in CuZn-SOD Tg mice, with a corresponding attenuation of liver enzyme release into plasma. Exogenously administered SOD had little or no effect on gut I/R-induced leukostasis or capillary no-reflow in the liver. These observations suggest a role for superoxide in gut I/R-induced leukostasis and hypoxic stress in the liver. Furthermore, the findings suggest that cellular localization of SOD activity is an important determinant of the protective actions of this enzyme in experimental models of I/R injury.
Department of Molecular and Cellular Physiology, Louisiana State University Medical Center, Shreveport, LA 71130-3992, USA.
Y
Y
Horie
R
R
Wolf
S C
SC
Flores
J M
JM
McCord
C J
CJ
Epstein
D N
DN
Granger
D000704:Analysis of Variance; D000818:Animals; D002196:Capillaries / Q000503:physiopathology; D004198:Disease Susceptibility; D007422:Intestines / Q000098:blood supply*; D018921:Leukostasis / Q000201:enzymology*; D008099:Liver / Q000098:blood supply*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D015427:Reperfusion Injury / Q000150:complications*; D013482:Superoxide Dismutase / Q000378:metabolism*
D013482:Superoxide Dismutase