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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° 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 …