The aim of the present study was to investigate the protective effect of the
peroxynitrite decomposition catalyst 5,10,15, 20-tetrakis(2,4,6-trimethyl-3,5-disulfonatophenyl)-porphyrinato
iron (III) (
FeTMPS) in a model of splanchnic artery occlusion
shock (SAO). SAO
shock was induced in rats by clamping both the superior mesenteric artery and the celiac trunk for 45 min, followed by release of the clamp (reperfusion). At 60 min after reperfusion, animals were killed for histological examination and biochemical studies. There was a marked increase in the oxidation of
dihydrorhodamine 123 to
rhodamine (a marker of
peroxynitrite-induced oxidative processes) in the plasma of the SAO-shocked rats after reperfusion, but not during
ischemia alone. Immunohistochemical examination demonstrated a marked increase in the immunoreactivity to
nitrotyrosine, an index of
nitrogen species such as
peroxynitrite, in the necrotic ileum in shocked rats. SAO-shocked rats developed a significant increase of tissue
myeloperoxidase and
malonaldehyde activity, and marked histological injury to the distal ileum. SAO
shock was also associated with a significant mortality (0% survival at 2 h after reperfusion). Reperfused ileum tissue sections from SAO-shocked rats showed positive staining for
P-selectin localized mainly in the vascular endothelial cells. Ileum tissue sections obtained from SAO-shocked rats and stained with antibody to
ICAM-1 showed a diffuse staining. Administration of
FeTMPS significantly reduced
ischemia/reperfusion injury in the bowel, and reduced
lipid and the production of
peroxynitrite during reperfusion. Treatment with PN catalyst also markedly reduced the intensity and degree of
P-selectin and
ICAM-1 staining in tissue sections from SAO-shocked rats and improved survival. Our results clearly demonstrate that
peroxynitrite decomposition catalysts exert a protective effect in SAO and that this effect may be due to inhibition of the expression of adhesion molecules and the tissue damage associated with
peroxynitrite-related pathways.