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.
Bielecki
K
K
Medizinische Poliklinik, University of Würzburg, Germany.
Wiedmann
M
M
Meyer
F
F
Kimura
W
W
Mössner
J
J
D000208:Acute Disease; D000681:Amylases / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D005472:Fluorouracil / Q000494:pharmacology*; D008297:Male; D009336:Necrosis; D010179:Pancreas / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010195:Pancreatitis / Q000201:enzymology* / Q000378:metabolism; D010477:Perfusion; D014176:Protein Biosynthesis; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley; D013656:Taurocholic Acid / Q000494:pharmacology
D013656:Taurocholic Acid; D012313:RNA; D000681:Amylases; D005472:Fluorouracil