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Non-conjugated chenodeoxycholate induces severe mitochondrial damage and inhibits bicarbonate transport in pancreatic duct cells
  1. J Maléth1,
  2. V Venglovecz2,
  3. Zs Rázga3,
  4. L Tiszlavicz3,
  5. Z Rakonczay Jr1,
  6. P Hegyi1
  1. 1First Department of Medicine
  2. 2Department of Pharmacology and Pharmacotherapy
  3. 3Department of Pathology, University of Szeged, Szeged, Hungary
  1. Correspondence to Dr Péter Hegyi, First Department of Medicine, University of Szeged, Faculty of Medicine, PO Box 427, H-6701 Szeged, Hungary; hep{at}in1st.szote.u-szeged.hu

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We read the manuscripts by Lee and Muallem1 and Venglovecz et al2 recently published in Gut with great interest. In both articles the authors highlighted the role of pancreatic ducts in maintaining the integrity of the pancreas. Venglovecz et al showed that a high concentration of the non-conjugated chenodeoxycholate (CDC) inhibits pancreatic ductal bicarbonate secretion; however, the mechanisms of the inhibition were not clarified. This is a follow-up study in which we show that this reduction of ductal bicarbonate secretion by CDC is evoked by inhibition of glycolytic and oxidative (caused by severe mitochondrial damage) metabolism with a consequent depletion of intracellular ATP levels.

Physiologically, pancreatic ductal fluid and HCO3 secretion are necessary to wash out the digestive enzymes from the acinar cells into the duodenum. Under pathophysiological conditions toxic factors (such as bile acids and ethanol) involved in the pathogenesis of acute pancreatitis have dual effects on ductal HCO3 secretion.1 Low doses of CDC and ethanol were found to stimulate fluid and HCO3 secretion. However, these toxic agents in high concentrations inhibit the secretion. These data suggest that an elevation in pancreatic ductal fluid and HCO3 secretion may have protective roles. However, since under physiological conditions the pressure in the main pancreatic duct is higher than in the bile ducts, it is still controversial as to whether bile acids enter the pancreatic ductal tree.

We have recently shown that a high concentration (1 mM) of the non-conjugated bile acid CDC has strong inhibitory effects on the activities of acid/base transporters (Na+/H+ exchanger (NHE), Na+/HCO3 cotransporter (NBC) …

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