Beneficial effects of peroxynitrite decomposition catalyst in a rat model of splanchnic artery occlusion and reperfusion

The aim of the present study was to investigate the protective effect of th e peroxynitrite decomposition catalyst 5,10,15,20-tetrakis(2,4,6-trimethyl- 3,5-disulfonatophenyl)-porphyrinato iron (III) (FeTMPS) in a model of splan chnic artery occlusion shock (SAO). SAO shock was induced in rats by clampi ng both the superior mesenteric artery and the celiac trunk for 45 min, fol lowed by release of the clamp (reperfusion). At 60 min after reperfusion, a nimals were killed for histological examination and biochemical studies. Th ere was a marked increase in the oxidation of dihydrorhodamine 123 to rhoda mine (a marker of peroxynitrite-induced oxidative processes) in the plasma of the SAO-shocked rats after reperfusion, but not during ischemia alone. I mmunohistochemica1 examination demonstrated a marked increase in the immuno reactivity to nitrotyrosine, an index of nitrogen species such as peroxynit rite, in the necrotic ileum in shocked rats. SAG-shocked rats developed a s ignificant increase of tissue myeloperoxidase and malonaldehyde activity, a nd marked histological injury to the distal ileum. SAO shock was also assoc iated with a significant mortality (0% survival at 2 h after reperfusion). Reperfused ileum tissue sections from SAG-shocked rats showed positive stai ning for P-selectin localized mainly in the vascular endothelial cells. Ile um tissue sections obtained from SAO-shocked rats and stained with antibody to ICAM-1 showed a diffuse staining. Administration of FeTMPS significantl y reduced ischemia/reperfusion injury in the bowel, and reduced lipid and t he production of peroxynitrite during reperfusion. Treatment with PN cataly st also markedly reduced the intensity and degree of P-selectin and ICAM-1 staining in tissue sections from SAG-shocked rats and improved survival. Ou r results clearly demonstrate that peroxynitrite decomposition catalysts ex ert a protective effect in SAO and that this effect may be due to inhibitio n of the expression of adhesion molecules and the tissue damage associated with peroxynitrite-related pathways.-Cuzzocrea S., Misko, T. P., Costantino , C., Mazzon, E., Micali, A., Caputi, A. P., Macarthur, H., Salvemini, D. B eneficial effects of peroxynitrite decomposition catalyst in a rat model of splanchnic artery occlusion and reperfusion.