CHRONIC ETHANOL-CONSUMPTION INCREASES THE FRAGILITY OF RAT PANCREATICZYMOGEN GRANULES

Intracellular activation of pancreatic digestive enzymes by lysosomal hydrolases is thought to be an early event in the pathogenesis of panc reatic injury. As ethanol excess is an important association of pancre atitis, experimental work has been directed towards exploring possible mechanisms whereby ethanol may facilitate contact between inactive di gestive enzyme precursors and lysosomal enzymes. The aim of this study was to find out if chronic ethanol administration increases the fragi lity of rat pancreatic zymogen granules. Sixteen male Sprague-Dawley r ats were pair fed ethanol and control liquid diets Zymogen granule fra gility assessed in pancreatic homogenate by determination of (a) laten cy 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 an imals suggesting increased zymogen granule fragility. In support of th is finding, there was a trend towards increased supernatant enzyme aft er ethanol feeding. In conclusion, administration of ethanol increases the fragility of pancreatic zymogen granules in the absence of morpho logical evidence of pancreatic injury. It is proposed that zymogen gra nule fragility may play an early part in the pathogenesis of alcoholic pancreatitis by permitting contact between digestive and lysosomal en zymes.