Effect of 5-Fluorouracil on Secretion and Synthesis of Pancreatic Digestive Enzymes: Studies in Isolated Pancreatic Acini and Perfused Pancreas Derived from Normal Rats and from Rats with Acute Necrotizing Pancreatitis

Abstract

Summary

5-Fluorouracil (5-FU) has been claimed to have beneficial effects in human pancreatitis because of its ability to inhibit protein synthesis and secretion. However, the effect of 5-FU has not been studied in the pancreas of animals in more detail and the data in human pancreatitis are mostly derived from uncontrolled studies. Thus, we studied potential short-term effects of 5-FU on protein synthesis and secretion in isolated pancreatic acini from normal rats and from rats with sodium tauro-cholate-induced pancreatitis. Furthermore, we used the isolated perfused pancreas, damaged by taurocholate, to study whether arterial perfusion with 5-FU has any beneficial effects. When pancreatic acini were incubated with various concentrations of 5-FU, CCK-8-stimulated amylase secretion was not altered. Furthermore, 5-FU had no short-term effects on protein synthesis. Protein synthesis and secretion was already markedly depressed in isolated pancreatic acini derived from rats with sodium taurocholate-induced pancreatitis. 5-FU did not further decrease protein synthesis or secretion. Retrograde injection of sodium taurocholate in the main pancreatic duct of the isolated perfused pancreas resulted in a steep increase of amylase and lipase in the portal effluate. Arterial perfusion with 5-FU had no influence on enzyme release into the portal blood. We may conclude that our data, derived from experimental pancreatitis in rats, do not encourage investigation of the effect of SFU, an anticancer drug with possibly toxic side effects, in human pancreatitis.