Effects of endogenous acetaldehyde production by disulfiram and ethanol feeding on rat pancreas |
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Authors: | Zhi-Jun He MD Peter Eriksson PhD Hannu Alho MD Aimo Harmoinen PhD Isto Nordback MD |
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Institution: | (1) Department of Surgery, Tampere University Hospital, University of Tampere School of Medicine, Tampere;(2) Department of Clinical Chemistry, Tampere University Hospital, University of Tampere School of Medicine, Tampere;(3) Department of Menai Health and Alcohol Research, National Public Health Institute, Helsinki, Finland;(4) Department of Surgery, Tampere University Hospital, P.O. Box 2000, FIN-33521 Tampere, Finland |
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Abstract: | Exogenous acetaldehyde infusion can induce pancreatitis-like injury of the pancreas in some isolated pancreas models, whereas
in vivo such treatment has 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 after ethanol feeding when acetaldehyde metabolism is blocked by disulfiram, and
whether this treatment can induce pancreatitis-like injury in the rat. The liver was studied for comparison. In part I of
the experiment, adult male Wistar rats were given water (n = 24), ethanol (n = 24), disulfiram (n = 24), and ethanol plus
disulfiram for 1 week (n = 24) or 3 weeks (n = 24) and for 3 weeks with (n = 6) and without (n = 6) hypovolemia. In part II
of the experiment, rats were given water (n = 6), ethanol (n = 6), and high-dose disulfiram (n = 6) and ethanol plus high-dose
disulfiram (n = 6). Ethanol and acetaldehyde concentrations in blood, liver, and pancreas were measured. Animal behavior was
monitored, and weight changes, plasma amylase activity, water content, and histomorphology of the pancreas and liver were
studied without knowing the group. No increases in plasma amylase activity and no histomorphologic changes in the pancreas
were observed under light or electron microscopy in part I of the experiment. In part II, treatment with ethanol induced acetaldehyde
accumulation in the liver (33.6 ±2.6 (μmol/L), but to a lesser degree in the blood (9.6 ±1.6 μmol/L) and pancreas (5.0 ±1.2
μ,mol/L). Ethanol plus disulfiram induced marked accumulation of acetaldehyde in the liver (83.2 ±15.9 μmol/L), blood (280.0
±47.4 μnol/L), and pancreas (43.6 ±4.7 μ,mol/L). When tissue acetaldehyde levels reached 30 to 40 μ,mol/L, we found a decrease
in zymogen granules along with formation of small intracytoplasmic vacuolizations in the acinar cells and accumulation of
lipid droplets in the hepatocytes, whereas physiologic signs of pancreatitis (hyperatnylasemia, edema) or increases in liver
enzymes did not develop. High levels of acetaldehyde accumulate in the liver and pancreas w ith the treatment described. Although
this was accompanied by lipid degeneration of the hepatocytes and some subcellular changes in the acinar cells, physiologic
signs of pancreatitis did not develop. Thus acetaldehyde accumulation alone, or in combination with hypovolemia, is not responsible
for the induction of acute pancreatitis.
Supported by grants from the Paulo Foundation and the Medical Research Fund of Tampere University Hospital. |
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Keywords: | Acetaldehyde acute alcoholic pancreatitis disulfiram liver changes histopathology |
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