Intracellular activation of pancreatic digestive
enzymes by lysosomal
hydrolases is thought to be an early event in the pathogenesis of pancreatic injury. As
ethanol excess is an important association of
pancreatitis, experimental work has been directed towards exploring possible mechanisms whereby
ethanol may facilitate contact between inactive digestive
enzyme precursors and lysosomal
enzymes. The aim of this study was to find out if chronic
ethanol administration increases the fragility of rat pancreatic zymogen granules. Sixteen male Sprague-Dawley rats were pair fed
ethanol and control liquid diets for four weeks. Zymogen granule fragility was then assessed in pancreatic homogenate by determination of (a) latency and (b) per cent supernatant
enzyme after sedimentation of zymogen granules.
Amylase was used as a zymogen granule marker
enzyme. Latency was significantly reduced in pancreatic homogenates of
ethanol fed animals suggesting increased zymogen granule fragility. In support of this finding, there was a trend towards increased supernatant
enzyme after
ethanol feeding. In conclusion, administration of
ethanol increases the fragility of pancreatic zymogen granules in the absence of morphological evidence of pancreatic injury. It is proposed that zymogen granule fragility may play an early part in the pathogenesis of
alcoholic pancreatitis by permitting contact between digestive and lysosomal
enzymes.