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Effects of Intravenous Administration of Pentoxifylline in Pancreatic Ischemia/Reperfusion Injury
Edmond R. Campion, ANA Maria M. Coelho*, Marcel C. Machado, Sandra N. Sampietre, Nilza a. Molan, José Jukemura, Luiz C. D'Albuquerque
Gastroenterology, University of Sao Paulo, Sao Paulo, Brazil
Background/Aim: Therapeutics strategies to reduce pancreatic ischemic/reperfusion injury (I/R) might improve the outcome of human pancreatic-kidney transplantation. Pentoxifylline (PTX) beside its hemorrheologic effects has an anti-inflammatory effect by inhibiting NF-kappaB activation. We have previously demonstrated that PTX had anti-inflammatory response in acute pancreatitis and liver ischemia/reperfusion models. We have hypothesized that PTX could reduce pancreatic, renal lesions and the systemic inflammatory response in pancreatic I/R injury. The aim of this study was to evaluate the effect of PTX administration in a rat model of pancreatic I/R injury
Methods: Pancreatic ischemia was performed in Wistar rats during one hour by clamping the splenic vessels under mechanical ventilation. The vascular clamp was removed 1 hour after ischemia and pancreatic revascularization was achieved, followed by 4h or 24h of reperfusion. The animals submitted to ischemic/reperfusion were randomly divided into 2 groups: Group C (n=20): control, rats received saline solution IV, 45 minutes after ischemia, and Group P (n=20): rats received PTX (25mg/Kg) IV, 45 minutes after ischemia. Four and twenty four hours after reperfusion blood were collected for determinations of amylase, creatinine, TNF-α, IL-6, and IL-10. Pancreatic malondialdehyde (MDA) content was also performed. After 24hours of reperfusion pulmonary tissues were assembled for myeloperoxidade (MPO) analyses.
Results: A significant reduction in serum TNF-α, IL-6, IL-10, and creatinine levels was observed in PTX group compared to control group (p<0.05). No differences in pancreatic MDA content and in serum amylase levels were observed between two groups. Twenty-four hours after ischemia it was not observed any significant difference in the results of lung myeloperoxidase activity (MPO).
Conclusion: Pentoxifylline administration reduced the systemic inflammatory response and renal dysfunction in pancreatic I/R injury and could be a useful tool in pancreas-kidney transplantation
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