Fatty acid ethyl esters increase rat pancreatic lysosomal fragility.
Recent studies indicate that altered lysosomal function may be involved in the early stages of pancreatic injury. Chronic consumption of ethanol has been shown to increase rat pancreatic lysosomal fragility. Fatty acid ethyl esters (nonoxidative products of ethanol metabolism) accumulate in the pancreas after ethanol consumption. The aim of this study was to determine whether the lysosomal fragility observed after ethanol could be mediated by fatty acid ethyl esters. Rat pancreatic lysosomes were incubated for 20 minutes at 20 degrees C with ethyl oleate (a representative fatty acid ethyl ester). Lysosomal stability was then assessed by determination of (1) latency (i.e., the percent increase in lysosomal enzyme activity after addition of Triton X-100) and (2) supernatant activity (i.e., the proportion of lysosomal enzyme remaining in the supernatant after resedimentation of lysosomes). N-acetyl glucosaminidase and cathepsin B were assayed as lysosomal marker enzymes. Lysosomes incubated with buffer alone were used as controls. Ethyl oleate at concentrations above 140 mumol/L increased pancreatic lysosomal fragility as demonstrated by decreased latency. Increased percentage of enzyme in the supernatant was observed at higher concentrations. These results suggest that increased pancreatic lysosomal fragility observed with ethanol may be mediated by fatty acid ethyl esters.
Haber
P S
PS
Department of Gastroenterology, Prince Henry Hospital, Sydney, Australia.
Wilson
J S
JS
Apte
M V
MV
Pirola
R C
RC
D000118:Acetylglucosaminidase / Q000032:analysis; D000818:Animals; D002403:Cathepsins / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000032:analysis; D008247:Lysosomes / Q000201:enzymology / Q000502:physiology* / Q000648:ultrastructure; D008297:Male; D017830:Octoxynol; D009829:Oleic Acids / Q000494:pharmacology*; D010179:Pancreas / Q000648:ultrastructure*; D011092:Polyethylene Glycols; D051381:Rats; D017207:Rats, Sprague-Dawley
D005230:Fatty Acids, Nonesterified; D009829:Oleic Acids; D000431:Ethanol; D011092:Polyethylene Glycols; D017830:Octoxynol; D000118:Acetylglucosaminidase; D002403:Cathepsins; C033180:ethyl oleate