Intestinal post-ischemic reperfusion injury: studies with neonatal necrotizing enterocolitis.
In the feline intestine studies have implicated superoxide (O.-) and other oxygen derived free radicals as initiators of injury as measured by increased capillary permeability during the reperfusion period. Biochemical mechanisms of this free radical generation include: xanthine oxidase dependent O.- production, hydrogen peroxide (H2O2) formation by superoxide dismutase (SOD), hydroxyl radical (OH-) production via the Haber-Weiss reaction, and lipid radical formation from membrane peroxidation. Pathological consequences of these events include inflammatory neutrophil infiltration, damage to the collagen and mucosal basement membrane, increased capillary permeability, edema, cell degeneration and necrosis. Animal models of neonatal necrotizing enterocolitis (NNEC) indicate that intestinal injury occurs after the etiologic factors (hypothermia, hypoxia) are removed. In order to determine the role of active oxygen species in the pathogenesis of NNEC, weanling hamsters and neonatal piglets were cold stressed and activities of pro/antioxidant enzymes were determined, and histopathologic and ultrastructural studies were performed. Cold stressed weanling hamsters showed a 55.7% (P less than 0.05) decrease in xanthine dehydrogenase/xanthine oxidase activity ratio. Light microscopy revealed scattered colonic mucosal erosions and submucosal edema in 50% of cold stressed animals. Transmission electron microscopy demonstrated degeneration of colonic mucosal epithelial cells, enlarged intracellular spaces, cytoplasmic vacuolization, and nuclear membrane swelling. The colonic serosa was also edematous and infiltrated with bacteria. Large intestinal tissue from cold stressed neonatal piglets showed a significant increase (P less than 0.05) in Mn and Cu, Zn, SOD, CAT, GSH-Red, total GSH, and Glc6-PD at 0 and 12 hrs. post stress.(ABSTRACT TRUNCATED AT 250 WORDS)
Cassutto
B H
BH
Department of Veterinary Biosciences, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic and State University, Blacksburg 24061.
Misra
H P
HP
Pfeiffer
C J
CJ
D000818:Animals; D000831:Animals, Newborn; D006224:Cricetinae; D004761:Enterocolitis, Pseudomembranous / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D005609:Free Radicals; D007422:Intestines / Q000098:blood supply* / Q000648:ultrastructure; D010100:Oxygen / Q000378:metabolism; D015427:Reperfusion Injury / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D014969:Xanthine Oxidase / Q000502:physiology
D005609:Free Radicals; D014969:Xanthine Oxidase; D010100:Oxygen