Abstract
We have previously demonstrated that β-3-thienylalanine (β3TA), an analogue of phenylalanine, inhibits zymogen granule formation in pancreatic acinar cells in rats. That such inhibition of zymogens might prevent drug-induced pancreatitis was studied in the experimental model of ethionine pancreatitis. 14 Sprague Dawley rats were divided into 2 groups. Group I was given a maintenance amino acid diet for 3 days and then a diet containing equimolar substitution of ethionine for methionine for 8 days. Group II received this same diet but with a 3 × equimolar substitution of β3TA for phenylalanine for 3 days, followed by a 1 × equimolar substitution for 8 days while on ethionine. The animals were killed and tissues prepared for microscopic examination. Group I rats demonstrated severe pancreatitis; group II showed few such changes. Another study was done in identical manner with rats being killed 3 days after initiation of ethionine feeding. Engorgement of acini with zymogens and early pyknosis appeared to precede the development of pancreatitis in rats not receiving β3TA. Rats receiving this analogue showed complete zymogen suppression and no pancreatitis. A 9 × equimolar dose of β3TA administered over a 24-hour period was fatal to rats receiving such high concentrations. β3TA may prevent ethionine pancreatitis through its zymogen suppressive effect.
Published Version
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