ETHANOL-INDUCED ALTERATIONS IN MESSENGER-RNA LEVELS CORRELATE WITH GLANDULAR CONTENT OF PANCREATIC-ENZYMES

Ethanol abuse Is a well-known association of pancreatitis. The effects of chronic ethanol consumption on pancreatic digestive and lysosomal enzymes may be relevant to the pathogenesis of alcoholic pancreatitis, because pancreatic enzymes play an important role in the development of pancreatic injury, The aims of this study were to determine the eff ects of ethanol on gene expression and glandular content of pancreatic digestive enzymes and on gene expression of the lysosomal enzyme cath epsin B (known to be capable of activating trypsinogen), Pancreatic co ntent and mRNA levels for lipase, trypsinogen, and chymotrypsinogen we re determined in rats that were pair-fed a nutritionally adequate liqu id diet with or without ethanol for 4 weeks, mRNA levels for the lysos omal enzyme cathepsin B were also assessed in this model, Ethanol sign ificantly increased the content of lipase in the pancreas. There was a trend toward an increase in trypsinogen and chymotrypsinogen levels; however, these differences were not statistically significant, mRNA le vels for lipase, trypsinogen, and chymotrypsinogen were raised in etha nol-fed rats, Ethanol feeding also increased mRNA levels for the lysos omal enzyme cathepsin B, Furthermore, there was a close, statistically significant correlation between changes in mRNA levels and tissue act ivities of pancreatic digestive and lysosomal enzymes after ethanol co nsumption. These results suggest that ethanol increases the capacity o f the pancreatic acinar cell to synthesize digestive and lysosomal enz ymes, thereby increasing the susceptibility of the gland to enzyme-rel ated injury.