Effects of endogenous acetaldehyde production by disulfiram and ethanol feeding on rat pancreas

Exogenous acetaldehyde infusion can induce pancreatitis-like injury of the pancreas in some isolated pancreas models, whereas in vivo such treatment h as failed to induce pancreatitis. In vivo exogenous acetaldehyde may not be effective because it is rapidly metabolized. The aim of this study was to investigate whether endogenous acetaldehyde accumulates in the pancreas aft er ethanol feeding when acetaldehyde metabolism is blocked by disulfiram, a nd whether this treatment can induce pancreatitis-like injury in the rat. T he liver was studied for comparison. In part I of the experiment, adult mal e Wistar rats were given water (n = 24), ethanol (n = 24), disulfiram (n = 24), and ethanol plus disulfiram for I week (n = 24) or 3 weeks (n = 24) an d for 3 weeks with (n = 6) and without (n = 6) hypovolemia. In part IT of t he experiment, rats were given water (n = 6), ethanol (n = 6), and high-dos e disulfiram (n = 6) and ethanol plus high-dose disulfiram (n = 6). Ethanol and acetaldehyde concentrations in blood, liver, and pancreas were measure d. Animal behavior was monitored, and weight changes, plasma amylase activi ty, water content, and histomorphology of the pancreas and liver were studi ed without knowing the group. No increases in plasma amylase activity and n o histomorphologic changes in the pancreas were observed under light or ele ctron microscopy in part I of the experiment. In part II, treatment with et hanol induced acetaldehyde accumulation in the liver (33.6 +/- 2.6 mu mol/L ), but to a lesser degree in the blood (9.6 +/- 1.6 mu mol/L) and pancreas (5.0 +/- 1.2 mu mol/L). Ethanol plus disulfiram induced marked accumulation of acetaldehyde in the liver (83.2 +/- 15.9 mu mol/L), blood (280.0 +/- 47 .4 mu mol/L), and pancreas (43.6 +/- 4.7 mu mol/L). When tissue acetaldehyd e levels reached 30 to 40 mu mol/L, we found a decrease in zymogen granules along with formation of small intracytoplasmic vacuolizations in the acina r cells and accumulation of lipid droplets in the hepatocytes, whereas phys iologic signs of pancreatitis (hyperamylasemia, edema) or increases in live r enzymes did not develop. High levels of acetaldehyde accumulate in the li ver and pancreas with the treatment described. Although this was accompanie d by lipid degeneration of the hepatocytes and some subcellular changes in the acinar cells, physiologic signs of pancreatitis did not develop. Thus a cetaldehyde accumulation alone, or in combination with hypovolemia, is not responsible for the induction of acute pancreatitis.