Peroxynitrite decomposition catalyst FeTMPyP provides partial protection against intestinal ischemia and reperfusion injury in infant rats.
Free radicals are important in development of intestinal ischemia-reperfusion (I/R) injury, leading to intestinal and pulmonary damage. We evaluated the effects of peroxynitrite decomposition catalyst FeTMPyP in infant intestinal I/R. Suckling rats underwent 40 min intestinal ischemia + 90 min reperfusion. At reperfusion, animals received saline or FeTMPyP. Groups were (n = 11 per group): 1) control+saline; 2) I/R+saline; 3) I/R+FeTMPyP. Increased histologic injury and ICAM-1 expression were observed in ileum of both I/R+saline and I/R+FeTMPyP rats, but P-selectin expression was increased in I/R+saline animals only versus controls. Myeloperoxidase (neutrophil infiltration marker) was increased in ileum and lungs of I/R+saline rats, but FeTMPyP prevented this in the ileum. I/R+saline animals showed higher malondialdehyde (lipid peroxidation marker) in ileum and lungs versus both control+saline and I/R+FeTMPyP rats. Glutathione was decreased in all I/R animals, but oxidized and total glutathione were higher in I/R+FeTMPyP than the I/R+saline group. Nitrate+nitrite concentration (systemic nitric oxide production) was elevated in I/R+saline but not in I/R+FeTMPyP animals. FeTMPyP provides limited protection against intestinal I/R in neonatal rats by reducing ileal P-selectin expression, systemic nitric oxide production, neutrophil infiltration in ileum and lipid peroxidation in both lungs and ileum; and preserving intestinal antioxidant capacity.
Stefanutti
Giorgio
G
Units of Paediatric Surgery, Institute of Child Health, London, WC1N 1EH, United Kingdom.
Pierro
Agostino
A
Smith
Virpi V
VV
Klein
Nigel J
NJ
Eaton
Simon
S
D000818:Animals; D000833:Animals, Suckling; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D007511:Ischemia / Q000517:prevention & control*; D008315:Malondialdehyde / Q000378:metabolism; D008665:Metalloporphyrins / Q000378:metabolism / Q000494:pharmacology; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D015427:Reperfusion Injury / Q000517:prevention & control*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
C492721:5,10,15,20-tetrakis(N-methyl-4'-pyridyl)porphyrinato-iron(III); D008665:Metalloporphyrins; D009566:Nitrates; D009573:Nitrites; D019007:P-Selectin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D030421:Peroxynitrous Acid; D008315:Malondialdehyde; D009195:Peroxidase; D005978:Glutathione