Beneficial effects of melatonin 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 pineal secretary product melatonin in a model of splanchnic artery occlus ion shock (SAO). SAO shock was induced in rats by damping both the superior mesenteric artery and the celiac trunk for 45 min, followed thereafter by release of the clamp (reperfusion). At 60 min after reperfusion, animals we re sacrificed for tissue histological examination and biochemical studies. There was a marked increase in the oxidation of dihydrorhodamine 123 to rho damine (a marker of peroxynitrite-induced oxidative processes) in the plasm a of the SAG-shocked rats after reperfusion, but not during ischemia alone. Immunohistochemical examination demonstrated a marked increase in the immu noreactivity to nitrotyrosine, an index of nitrogen species such as peroxyn itrite, in the necrotic ileum in shocked rats. SAG-shocked rats developed a significant increase of tissue myeloperoxidase and malondialdehyde activit y, and marked histological injury to the distal ileum. SAO shock was also a ssociated with a significant mortality (0%, survival at 2 hr after reperfus ion). Reperfused ileum tissue sections from SAG-shocked rats showed positiv e staining for P-selectin, which was mainly localized in the vascular endot helial cells. Ileum tissue sections obtained from SAG-shocked rats with ant i-intercellular adhesion molecule (ICAM-1) antibody showed a diffuse staini ng. Melatonin (applied at 3 mg/kg, 5 min prior to reperfusion, followed by an infusion of 3 mg/kg per hr), significantly reduced ischemia/reperfusion injury in the bowel as evaluated by histological examination. This prevente d the infiltration of neutrophils into the reperfused intestine, as evidenc ed by reduced myeloperoxidase activity and reduced lipid peroxidation. This was evaluated by malondialdehyde activity which reduced the production of peroxynitrite during reperfusion, markedly reduced the intensity and degree of P-selectin and ICAM-1 in tissue section from SAG-shocked rats and impro ved their survival. Taken together, our results clearly demonstrate that me latonin treatment exerts a protective effect and part of this effect may be due to inhibition of the expression of adhesion molecule and peroxynitrite -l-elated pathways and subsequent reduction of neutrophil-mediated cellular injury.