Effects of the tyrosine kinase inhibitor tyrphostin AG 556 on acute necrotising pancreatitis in rats.

Abstract

Objective: To investigate the effects of the tyrosine kinase inhibitor tyrphostin AG 556 on the course of acute necrotising pancreatitis in rats.

Design: Laboratory study.

Setting: Medical school, Turkey.

Animals: 72 Sprague Dawley rats, 12 in the sham operated (control) group and 20 in each of the three others.

Main outcome measures: Cardiorespiratory measurements, mortality, effect on the activities of various enzymes in serum and tissue of pancreas and lung, and the histological picture.

Results: The four study groups were sham + Ringer's lactate, acute necrotising pancreatitis with Ringer's lactate, tryphostin AG 556, and dimethylsulfoxide (DMSO). There were 12 animals in the first group and 20 in each of the other groups. The induction of pancreatitis increased mortality from 0/12 in the control to 6/20 (30%), 7/20 (35%), 8/20 (40%) in the three experimental groups, respectively. Heart rate, packed cell volume (PCV), serum activities of amylase and alanine aspartate transferase, tissue activity of myeloperoxidase (MPO) and malondialdehyde (MDA) in the pancreas and lung, serum concentrations of urea and calcium, volume of ascites, degree of pancreatic damage, blood pressure, and urine production did no differ between the pancreatitis groups.

Conclusions: Treatment with the tyrphostin kinase inhibitor did not improve the course of acute pancreatitis or reduce the extent of acinar cell injury and is therefore unlikely to be of benefit in patients with pancreatitis.