Irreversible exocrine pancreatic insufficiency in alcoholic rats without chronic pancreatitis after alcohol withdrawal.
BACKGROUND
Long-term alcohol consumption alone did not cause chronic pancreatitis (CP) but impaired exocrine pancreatic function. This study is to explore the reversibility of exocrine pancreatic insufficiency in the abstinent rats and its mechanism.


METHODS
Forty-eight healthy male Wistar rats were divided randomly into 4 groups: 6-month control, 6-month ethanol, 9-month control, and 9-month ethanol + withdrawal. Morphological changes of pancreatic acinar cells were observed. Pancreatic amylase and lipase were measured using an automatic biochemical analyzer. Free fatty acid (FFA) in rat intestinal chyme was measured. Cholecystokinin (CCK) levels were determined by radioimmunoassay. The expression of CCK-A receptors was quantitatively analyzed by Western blot.


RESULTS
Alcohol-induced ultramicrostructure changes of pancreatic acinar cells, including lipid droplets, myelinoid inclusion bodies, dilated rough endoplasmic reticulums, and diminished zymogen granules, were not attenuated after alcohol abstinence. The outputs of amylase and lipase, FFA content in intestinal chyme, and the intestinal and the pancreatic CCK levels in rats were reduced after chronic alcohol intake and were still lower than the control after cessation of alcohol use. Chronic ethanol intake or abstinence did not induce any change in the expression of CCK-A receptors.


CONCLUSIONS
Exocrine pancreatic insufficiency was irreversible in alcoholic rats without CP after alcohol withdrawal. It may be attributed to reduced pancreatic CCK, long-standing fatty infiltration, ultramicrostructure injuries in pancreatic acinar cells, and aging.
Li
Jing
J
Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, China.
Zhou
Chao
C
Wang
Rui
R
Liu
Rui
R
Huang
Zhiyin
Z
Tang
Chengwei
C
D000437:Alcoholism / Q000473:pathology*; D000681:Amylases / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002492:Central Nervous System Depressants / Q000097:blood; D002766:Cholecystokinin / Q000378:metabolism; D002149:Energy Intake / Q000502:physiology; D000431:Ethanol / Q000097:blood; D010188:Exocrine Pancreatic Insufficiency / Q000139:chemically induced*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism; D008049:Lipase / Q000378:metabolism; D008297:Male; D010179:Pancreas / Q000201:enzymology / Q000473:pathology; D010195:Pancreatitis / Q000150:complications*; D050500:Pancreatitis, Chronic / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D043886:Receptor, Cholecystokinin A / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000473:pathology*; D014280:Triglycerides / Q000378:metabolism; D015430:Weight Gain / Q000502:physiology
D002492:Central Nervous System Depressants; D005230:Fatty Acids, Nonesterified; D043886:Receptor, Cholecystokinin A; D014280:Triglycerides; D000431:Ethanol; D002766:Cholecystokinin; D008049:Lipase; D000681:Amylases