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.

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 taurocholate-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 5-FU, an anticancer drug with possibly toxic side effects, in human pancreatitis.