Search

Abstract  The pancreas is vulnerable to ethanol toxicity, but the pathogenesis of alcoholic pancreatitis is not fully defined. The intracellular oxidative balance and the characteristics of the secretion of isolated rat pancreatic acinar cells stimulated with the cholecystokinin analogue cerulein were assayed after acute oral ethanol (4 g/kg) load. Pancreatic acinar cells from ethanol-treated rats showed a significant (p p p  [ABSTRACT FROM AUTHOR]

Gastroduodenal toxicity of nonsteroidal anti-inflammatory drugs (NSAIDs) is partly independent from cyclooxygenase inhibition, possibly related to increased intermixed micellar–vesicular (nonphospholipid–associated) bile salt concentrations thought to be responsible for bile salt cytotoxicity. We evaluated the effects of indomethacin on bile salt cytotoxicity with complementary in vitro and ex vivo systems. In the erythrocyte model, indomethacin alone did not induce hemolysis. In contrast, indomethacin enhanced and phospholipids decreased hemolysis induced by hydrophobic taurodeoxycholate (TDC). Hydrophilic tauroursodeoxycholate (TUDC) enhanced rather than decreased TDC-induced hemolysis in the presence of indomethacin. Indomethacin did not affect intermixed micellar–vesicular bile salt concentrations or compositions. Indomethacin also increased TDC-induced lactate dehydrogenase release in CaCo-2 cells and bile salt-induced rat colonic mucosal injury, and prevented potential protective effects of TUDC in these systems. Our data show that indomethacin enhances bile salt–induced cytotoxicity without affecting intermixed micellar–vesicular bile salt concentrations or compositions. These findings may be relevant for gastroduodenal injury during NSAID therapy. [ABSTRACT FROM AUTHOR]