Effects of intravenous administration of pentoxifylline in pancreatic ischaemia-reperfusion injury.

Background: Therapeutic strategies to reduce the occurrence of pancreatic ischaemia-reperfusion (I-R) injury might improve outcomes in human pancreas and kidney transplantation. In addition to its haemorrheologic effects, pentoxifylline has an anti-inflammatory effect by inhibiting NF-κB activation. This group has previously demonstrated that pentoxifylline induces an anti-inflammatory response in acute pancreatitis and liver I-R models. This led to the hypothesis that pentoxifylline might reduce pancreatic and renal lesions and the systemic inflammatory response in pancreatic I-R injury. The aim of this experimental study was to evaluate the effect of pentoxifylline administration in a rat model of pancreatic I-R injury.

Methods: Pancreatic I-R was performed in Wistar rats over 1 h by clamping the splenic vessels. The animals submitted to I-R were divided into two groups: Group 1 (n = 20, control) rats received saline solution administered i.v. at 45 min after ischaemia, and Group 2 (n = 20) rats received pentoxifylline (25 mg/kg) administered i.v. at 45 min after ischaemia. Blood samples were collected to enable the determination of amylase, creatinine, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-10. Pancreatic malondialdehyde (MDA) content, pancreas histology and pulmonary myeloperoxidase (MPO) were also assessed.

Results: Significant reductions in serum TNF-α, IL-6 and IL-10 were observed in Group 2 compared with Group 1 (P < 0.05). No differences in pancreatic MDA content or serum amylase levels were observed between the two groups. The histologic score was significantly lower in pentoxifylline-treated animals, denoting less severe pancreatic histologic damage.

Conclusions: Pentoxifylline administration reduced the systemic inflammatory response, the pancreatic histological lesion and renal dysfunction in pancreatic I-R injury and may be a useful tool in pancreas and kidney transplantation.