TRANSGENIC MICE WITH INCREASED COPPER ZINC SUPEROXIDE-DISMUTASE ACTIVITY ARE RESISTANT TO HEPATIC LEUKOSTASIS AND CAPILLARY NO-REFLOW AFTERGUT ISCHEMIA/REPERFUSION/

The objectives of this study were to (1) determine whether transgenic (Tg) mice overexpressing copper/zinc-superoxide dismutase (CuZn-SOD) a re protected from the deleterious effects of gut ischemia/reperfusion (VR) and (2) compare the effectiveness of Tg SOD overexpression in att enuating I/R injury to intravascularly administered CuZn-SOD or mangan ese (Mn)-SOD, The accumulation of fluorescently labeled leukocytes and number of nonperfused sinusoids were monitored by intravital microsco py in livers of wild-type mice (C57BL/6), CuZn-SOD Tg mice, and wild-t ype mice receiving either CuZn-SOD or Mn-SOD. All parameters were meas ured for 1 hour after release of the occluded (for 15 minutes) superio r mesenteric artery. Gut I/R in wild-type mice led to an increased num ber of stationary leukocytes, while reducing the number of perfused si nusoids (capillary no-reflow). All of these responses were significant ly blunted in CuZn-SOD Tg mice, with a corresponding attenuation of li ver enzyme release into plasma. Exogenously administered SOD had littl e or no effect on gut I/R-induced leukostasis or capillary no-reflow i n the liver. These observations suggest a role for superoxide in gut I /R-induced leukostasis and hypoxic stress in the liver. Furthermore, t he findings suggest that cellular localization of SOD activity is an i mportant determinant of the protective actions of this enzyme in exper imental models of I/R injury.