Abstract
Omeprazole (OME) has been shown to reduce liver regeneration and enhance gastrin serum levels. Since gastrin inhibits biliary growth, we tested the hypothesis that omeprazole inhibits cholangiocyte proliferation in BDL rats by increasing gastrin serum levels.MethodsIn vivo, male Fischer 344 rats (immediately BDL) were treated with vehicle or OME (40 mg/Kg BW daily) for 1 wk. We measured changes in: liver histology, and intrahepatic bile duct mass in liver sections; H3 histone and PCNA and secretin receptor (SR) gene expression; basal and secretin‐stimulated cAMP levels in cholangiocytes bile and bicarbonate secretion in bile fistula rats. Changes in SR and secretin‐stimulated secretion are key functional tools for evaluating the degree of biliary hyperplasia.ResultsChronic in vivo administration of OME to BDL rats increased gastrin serum levels and reduced biliary proliferation and hyperplasia and decreased SR expression and significantly inhibited the stimulatory effects of secretin on cAMP levels and ductal secretion compared to vehicle treated controls.ConclusionThe usage of OME may be important for the management of chronic cholestatic liver diseases.
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