Peroxynitrite decomposition catalyst FeTMPyP provides partial protection against intestinal ischemia and reperfusion injury in infant rats

Pediatr Res. 2007 Jul;62(1):43-8. doi: 10.1203/PDR.0b013e31806790c0.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Suckling
  • Endothelial Cells / cytology
  • Endothelial Cells / metabolism
  • Glutathione / metabolism
  • Intercellular Adhesion Molecule-1 / metabolism
  • Intestinal Mucosa* / metabolism
  • Intestines* / cytology
  • Intestines* / drug effects
  • Intestines* / pathology
  • Ischemia / prevention & control*
  • Malondialdehyde / metabolism
  • Metalloporphyrins* / metabolism
  • Metalloporphyrins* / pharmacology
  • Nitrates / metabolism
  • Nitrites / metabolism
  • P-Selectin / metabolism
  • Peroxidase / metabolism
  • Peroxynitrous Acid / metabolism*
  • Random Allocation
  • Rats
  • Reperfusion Injury / prevention & control*
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • 5,10,15,20-tetrakis(N-methyl-4'-pyridyl)porphyrinato-iron(III)
  • Metalloporphyrins
  • Nitrates
  • Nitrites
  • P-Selectin
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • Peroxynitrous Acid
  • Malondialdehyde
  • Peroxidase
  • Glutathione