FATTY-ACID ETHYL-ESTERS INCREASE RAT PANCREATIC LYSOSOMAL FRAGILITY

Recent studies indicate that altered lysosomal function may be involve d in the early stages of pancreatic injury. Chronic consumption of eth anol has been shown to increase rat pancreatic lysosomal fragility. Fa tty acid ethyl esters (nonoxidative products of ethanol metabolism) ac cumulate in the pancreas after ethanol consumption. The alm of this st udy was to determine whether the lysosomal fragility observed after et hanol could be mediated by fatty acid ethyl esters. Rat pancreatic lys osomes were incubated for 20 minutes at 20-degrees-C with ethyl oleate (a representative fatty acid ethyl ester). Lysosomol stability was th en assessed by determination of (1) latency (i.e., the percent increas e in lysosomal enzyme activity after addition of Triton X-100) and (2) supernatant activity (i.e., the proportion of lysosomal enzyme remain ing in the supernatant after resedimentation of lysosomes). N-acetyl g lucosaminidase and cathepsin B were assayed as lysosomal marker enzyme s. Lysosomes incubated with buffer alone were used as controls. Ethyl oleate at concentrations above 440 mumol/L increased pancreatic lysoso mal fragility as demonstrated by decreased latency. Increased percenta ge of enzyme in the supernatant was observed at higher concentrations. These results suggest that increased pancreatic lysosomal fragility o bserved with ethanol may be mediated by fatty acid ethyl esters.