Since the first evidence of the production of pancreatitis and liver cell damage by ethionine was made in rats by Farber and Popper(1950) and Goldberg et al.(1950), attentions were focused in the processes or the mechanisms of experimentally induced ethionine damages.
De Almeida and Grossman(1952) showed that the production of pancreatitis in dogs, cats and monkeys following administration of ethionine, which characterized by focal or diffuse necrosis of the acinar cells, interstitial inflammatory reaction and fat necrosis.
Other investigators studied the pathologic changes and metabolic antagonism after ethionine administration. The pathogenesis of the pancreatic lesion or liver cell damage is related to interference with some function of methionine metabolism since the changes are prevented by the simultaneous administration of methionine.
Also pancreatic enzymes content have been reported to be markedly increased in ethionine treated rats. Kahn and Carlson(1959) suggested that the caused of ethionine induced pancreatitis is an interference with the transport of proteolytic
enzymes from their intracellular position to the ductal system, by their experiment measuring membrane permeability with P**32 turnover in phospholipids. Kaufman et al.(1960) reported that excessive dietary methionine produced pancreatic damage which closely resembled that produced by small amounts of ethionine. Jackson(1925) described early that during total inanition the pancreas undergoes gross atrophy. The atrophy is due chiefly to an atrophy of the secretory acini, however, in the early stage the zymogen granules increase at the expense of the outer zoen with uncertain changes in the mitochondria.
Present study is concerned with the production of pancreatic or liver cell damage in rats following the administration of ethionine, methionine or fasting alone.
Studies of pancreatic and serum enzymes were made in various stages during fasting.
One hundred twenty six albino rats weighing approximately 150g each were divided into six experimental groups. The fist three groups, untreated control, ethionine, and methionine treated, were further divided into 6 subgroups of 6 animals per each subgroup. The remaining three groups of 6 animals per group were ethionine plus methionine, ethionine plus choline, and choline alone.
The rats were given aqueous dl-ethionine or dl-methionine intraperitoneally in a total dose of one mg per gram of body weight. Ethionie plus choline group received 0.5 mg per gram of body weight each. The choline group received 0.3 mg per gram of
body weight of choline alone.
The animals were fasted after the injection of ethionine or methionine. Water was permitted adlibitum in th animals fasted more than 24 hours and those animals were housed in individual cage.
The rats were sacrificed by exanguination from the femoral artery at 6, 2, 18, 24, 48 and 96 hours after the injection. The pancreas, liver and other organs were rapidly removed for either enzymatic or histologic study. The pancreas was homogenized in the cold acetone and made an acetone-ether extraction for enzyme
determination. The enzyme of pancreatic tissue powder were determined by the procedure described previously. Hematoxylin and eosin stained histologic section of the pancreas, liver and other organs and Sudan Ⅲ stained tissue fat.
Summary and Conclusion
Ethionine induced pancreatic and liver cell damages were studied in fasting rats given a single injection of large dose of ethionine or other amino acid with biochemical and histological technique.
1. Pancreatic enzyme content was progressively increased during inanition and the increased reached to the maximum value at the 24 hours after fasting. Thereafter the enzyme content was gradually decreased and the amylase was sharply decreased in
the animals fasted 96 hours.
2. Similar changes of pancreatic enzyme content during inanition as control group was showed in the animals given ethionine or methionine, howeve, the amylase content was reached to maximum at 24 hours and both lipase and trypsin content were
maximum at 48 hours in these animals. The rate of elevation of pancreatic enzyme was the highest in the animals given ethionine.
3. The pancreatic enzyme content after 48 hours inantion in the animals given ethionine plus methionine or ethionine plus choline was slightly low but elevated similarly as seen in ethionine alone.
4. The pancreatic enzyme content in animals given choline alone was equivalent of the content of control animals. Nevertheless, the rats given more than 0.5mg of choline per gram of body weight were expired within 12 hours.
5. The fall in serum amylase levels were seen in ethionine received rats and the fall reached to the maximum in the animals fasted 24 hours and thereafter the change was restored. Serum lipase was slightly elevated in either animals give ethionine or methionine.
6. Histologic findings revealed the early cloudy swelling and vacuolar degenerative changes of acinar cells and derangement of acini in the pancreas obtained at 6 hours after ethionine administration, and these changes reached to the maximum at 48 hours. The atrophy of acini and disorganized acinar cell were
appeared in pancreas obtained from the rats fasted for 96 hours after ethionine administration.
The light but similar features was observed in the pancreas of rats with inanition alone. The pancreatic changes are not differed by the simultaneous administration of methionine or choline to ethionine in such acute experiment.
7. The changes of liver cell consisted of cloudy swelling in early followed by the fatty changes with decreased of glycogen content in rats given ethionine.
(Partly supported by Grant No. 65-847, China Med. Board of New York)