A comparison of alcoholic pancreatitis in rat and man

Abstract

SUMMARY Acute ethanol intoxication was studied in 38 Wistar rats, 18 on a balanced dietand 20 on a high fat diet, fed by gavage on 47 % ethanol in a dosage of from 3 to 12 g/kg body weight daily for periods ranging from three to 16 days. No macroscopic changes in pancreas or liver were found in any of these animals. Histological changes (venous congestion of the pancreas, the liver, and the kidneys) were found in rats given 4 g or more per kilogram. The only difference between the findings in rats given a balanced diet and those given a high fat diet was the development of fatty livers in the latter group.Chronic ethanol intoxication was studied in 45 Wistar rats, on a balanced diet, which were given 20% ethanol freely for 20 to 30 months. More than half the animals developed pancreatic lesions very similar to those of human chronic pancreatitis. The pathological changes, in foci surrounded by normal pancreatic tissue, were a reduction in acini, duct multiplication (probably by neogenesis), protein plugs, sometimes calcified in the ducts and sclerosis. Samples of pancreatic juice from four animals exposed to ethanol contained significantly higher protein concentrations than samples taken from two control animals. Protein precipitates appeared spontaneously in the pancreatic juice of the animals exposed to ethanol, but not in that of the controls. These findings are very similar to those in alcoholic pancreatitis in man, which has thus been reproduced for the first time in experimental animals. Beta-cell adenomata of the islets of Langerhans were observed in four of the rats exposed to ethanol.

Effects of long term intravenous administration of ethanol on rat pancreas.

“…The theory proposed by Sarles et al (1971) that elevation in protein levels of the pancreatic juice is involved in the formation of protein plug could not be supported by the present findings. Although we did not confirm the formation of protein plug, there are many papers reporting the formation (IIashihira et al 1977;Nagata et al 1977).…”

“…From this viewpoint, the degeneration of mitochondria and an increase in lipid droplets observed in the groups treated with alcohol may be due to some cytotoxic effect of alcohol; in other words, the harmful effect of alcohol on the pancreatic metabolism. Similar to Sarles et al (1971), Dane et al (1970) gave alcohol to rats and made electron microscopic observations of the pancreas in function with time. Since they observed fatty degeneration of the acinar cells, swelling of mitochondria and the presence of FCD, they assumed that alcohol might give cytotoxic effect on the pancreas as well as on the liver.…”

“…Among previous studies, Huttunen et al (1976) collected pancreatic juice at the earliest period, namely 10 to 12 weeks after the start of administration of alcohol, given through a gastric tube and they observed a decrease in protein levels in the pancreatic juice. In the present study rats of oral-EtOH group received alcohol by the same method as that used by Sarles et al (1971) and Hashihira et al (1977). In these rats a decreased output of protein in basal secretion was recorded as early as 4 weeks after the start of the experiment.…”

“…In an experiment performed by Sarles et al (1971) in which rats were given 20% alcohol as drinking water, the mean intake of alcohol until rats grew to a body weight of 400 g was 4 g/rat/day. On the other hand, Dane et al (1970) reported that the mean daily alcohol intake was 0.5 to 1.2 g/100 g body weight in an experiment using various concentrations of alcohol.…”

“…The present findings indicate that the cytotoxic effect of alcohol on acinar cells and nutritional disorder associated with alcohol ingestion constitute important factors in the pathogenesis of chronic alcoholic pancreatitis. chronic pancreatitis; pancreatic exocrine function; intravenous administration of ethanol; protein plug As to the mechanism by which chronic alcoholic pancreatitis develops, various theories have been proposed such as hypersecretion-obstruction theory (Dreiling 1952), the theory of protein plug (Sarles et al 1971;Sarles 1974) and the theory of cytotoxicity (Darle et al 1970). As to the effect of alcohol on exocrine functions of the pancreas, it has been reported that orally ingested alcohol stimulates the pancreatic secretion secondary to the increase in the gastric acid secretion, while the alcohol transferred into the blood suppresses pancreatic secretion (Woodward et al 1957;Tiscornia et al 1972).…”