Influence of PACAP on oxidative stress and tissue injury following small-bowel autotransplantation.
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.
Ferencz
Andrea
A
Department of Surgical Research and Techniques, University of Pécs, Medical Faculty, Kodály Zoltán Street 20, 7624, Pecs, Hungary. andrea.ferencz@aok.pte.hu
Racz
Boglarka
B
Tamas
Andrea
A
Reglodi
Dora
D
Lubics
Andrea
A
Nemeth
Jozsef
J
Nedvig
Klara
K
Kalmar-Nagy
Karoly
K
Horvath
Ors Peter
OP
Weber
Gyorgy
G
Roth
Erzsebet
E
D000818:Animals; D003080:Cold Temperature; D006085:Graft Survival / Q000187:drug effects*; D006133:Growth Substances / Q000494:pharmacology*; D007421:Intestine, Small / Q000378:metabolism* / Q000637:transplantation*; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000378:metabolism / Q000494:pharmacology*; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D014021:Tissue Preservation; D014182:Transplantation, Autologous
D006133:Growth Substances; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide