Influence of PACAP on Oxidative Stress and Tissue Injury Following Small-Bowel Autotransplantation

Abstract

Tissue injury caused by cold preservation and reperfusion remains an unsolved problem during small-bowel transplantation. Pituitary adenylate cyclase-activating polypeptide (PACAP) is present and plays a central role in the intestinal physiology. This study investigated effect of PACAP-38 on the oxidative stress and tissue damage in autotransplanted intestine. Sham-operated, ischemia/reperfusion, and autotransplanted groups were established in Wistar rats. In ischemia/reperfusion groups, 1 h (group A), 2 h (group B), and 3 h (group C) ischemia followed by 3 h of reperfusion was applied. In autotransplanted groups, total orthotopic intestinal autotransplantation was performed. Grafts were preserved in University of Wisconsin (UW) solution and in UW containing 30 microg PACAP-38 for 1, 2, 3, and 6 h. Reperfusion lasted 3 h in all groups. Endogenous PACAP-38 concentration was measured by radioimmunoassay. To determine oxidative stress parameters, malondialdehyde, reduced glutathione, and superoxide dismutase were measured in tissue samples. Tissue damage was analyzed by qualitative and quantitative methods on hematoxylin/eosin-stained sections. Concentration of endogenous PACAP-38 significantly decreased in groups B and C compared to sham-operated group. Preservation solution containing PACAP-38 ameliorated bowel tissue oxidative injury induced by cold ischemia and reperfusion. Histological results showed that preservation caused destruction of the mucous, submucous, and muscular layers, which were further deteriorated by the end of reperfusion. In contrast, PACAP-38 significantly protected the intestinal structure. Ischemia/reperfusion decreased the endogenous PACAP-38 concentration in the intestinal tissue. Administration of PACAP-38 mitigated the oxidative injury and histological lesions in small-bowel autotransplantation model.

The effects of pituitary adenylate cyclase activating polypeptide in renal ischemia/reperfusion

“…PACAP injection. The results are in accordance with the findings of earlier studies, where the changes of SOD activity were measured in intestinal ischemia/reperfusion [8]. the protective effect of pacap has also been shown in oxidative stress-induced kidney injury in vitro [17].…”

“…This protective effect was first described in global and focal cerebral ischemia [32,42,48]. Subsequently, the protective effects of PACAP were reported in ischemic injury of the retina [4] and in ischemia/reperfusion-induced damages of peripheral organs, such as in intestinal, cardiac and liver ischemia/reperfusion [8,20,39].…”

Presence of Endogenous PACAP-38 Ameliorated Intestinal Cold Preservation Tissue Injury

“…The present observations are in accordance with our previous observations, where we have shown that adding exogenous PACAP-38 to UW solution prevented the elevation of lipid peroxidation and the reduction in endogenous scavenger capacity in rat small intestine. The intestinal structure was also significantly better preserved in small bowel autotransplantation model when PACAP-38 was added to the preservation solution (Ferencz et al 2009b). These observations support the role of PACAP-38 in tissue preservation in cold preservation model of transplantation.…”

“…These include primary graft non-or dysfunction, endotoxemia, peritonitis, and risk of acute/chronic rejection. Given the negative effect of this phenomenon, efforts are being made to recognize, modulate, minimize, or even eliminate it (Carden and Granger 2000;Ferencz et al 2009b;Balaz et al 2004;Mallick et al 2004Mallick et al , 2005.…”

Effects of PACAP on Mitochondrial Apoptotic Pathways and Cytokine Expression in Rats Subjected to Renal Ischemia/Reperfusion

“…PACAP has been shown to have protective effects against ischemia-induced tissue damage in the nervous system and also in the periphery, such as in the small intestine (Ferencz et al 2009;Ohtaki et al 2008). Ischemia/ reperfusion injury is characterized by common mechanisms in all tissues.…”