1.   Furthermore, recent studies from this laboratory have shown that experimental ethanol administration increases the fragility of rat pancreatic lysosomes.

2.   The aim of this study was to determine whether ethanol induced fragility of pancreatic lysosomes is mediated by ethanol, its oxidative metabolite acetaldehyde or cholesteryl esters.

3.   To study this question, the stability of pancreatic lysosomes was assessed after exposure in vitro to ethanol, acetaldehyde and the cholesteryl ester, cholesteryl oleate.

4.   Pancreatic lysosomes were isolated by a modification of the method of Ignarro et al as previously described.

5.   Experiments examining the effect of cholesteryl esters on the stability of isolated pancreatic lysosomes were carried out using cholesteryl oleate incorporated into phosphatidylcholine vesicles.

6.   The Table also indicates the proportion of lysosomal enzymes released into the supernatant after sedimentation of uncubated pancreatic lysosomes.

7.   Experimental ethanol administration results in increased fragility of pancreatic lysosomes and the simultaneous accumulation of cholesteryl esters in the pancrease.

8.   Ethanol induced fragility of pancreatic lysosomes has been observed in the absence of any morphologic evidence of pancreatic damage making it unlikely that it is a secondary phenomenon.

9.   This study shows that cholesteryl oleate can disrupt pancreatic lysosomes in vitro suggesting that cholesteryl esters may be responsible for the lysosomal fragility observed in vivo.