A novel, protective role of ursodeoxycholate in bile-induced pancreatic ductal injury

M. Katona, P. Hegyi, Balázs Kui, Zsolt Balla, Z. Rakonczay, Zsolt Rázga, L. Tiszlavicz, József Maléth, V. Venglovecz

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

We have previously shown that chenodeoxycholic acid (CDCA) strongly inhibits pancreatic ductal HCO3 - secretion through the destruction of mitochondrial function, which may have significance in the pathomechanism of acute pancreatitis (AP). Ursodeoxycholic acid (UDCA) is known to protect the mitochondria against hydrophobic bile acids and has an ameliorating effect on cell death. Therefore, our aim was to investigate the effect of UDCA pretreatment on CDCA-induced pancreatic ductal injury. Guinea pig intrainterlobular pancreatic ducts were isolated by collagenase digestion. Ducts were treated with UDCA for 5 and 24 h, and the effect of CDCA on intracellular Ca2+ concentration ([Ca2+]i), intracellular pH (pHi), morphological and functional changes of mitochondria, and the rate of apoptosis were investigated. AP was induced in rat by retrograde intraductal injection of CDCA (0.5%), and the disease severity of pancreatitis was assessed by measuring standard laboratory and histological parameters. Twenty- four-hour pretreatment of pancreatic ducts with 0.5 mM UDCA significantly reduced the rate of ATP depletion, mitochondrial injury, and cell death induced by 1 mM CDCA and completely prevented the inhibitory effect of CDCA on acid-base transporters. UDCA pretreatment had no effect on CDCA-induced Ca2+ signaling. Oral administration of UDCA (250 mg/kg) markedly reduced the severity of CDCA-induced AP. Our results clearly demonstrate that UDCA 1) suppresses the CDCA-induced pancreatic ductal injury by reducing apoptosis and mitochondrial damage and 2) reduces the severity of CDCA-induced AP. The protective effect of UDCA against hydrophobic bile acids may represent a novel therapeutic target in the treatment of biliary AP.

Original languageEnglish
Pages (from-to)G193-G204
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume310
Issue number3
DOIs
Publication statusPublished - 2016

Fingerprint

Chenodeoxycholic Acid
Ursodeoxycholic Acid
Bile
Pancreatitis
Wounds and Injuries
Pancreatic Ducts
Bile Acids and Salts
Mitochondria
Cell Death
Apoptosis
Collagenases
Oral Administration
Digestion
Guinea Pigs
Adenosine Triphosphate

Keywords

  • Acute pancreatitis
  • Chenodeoxycholic acid
  • Epithelial cells
  • Mitochondria
  • Ursodeoxycholic acid

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology (medical)
  • Physiology
  • Hepatology

Cite this

A novel, protective role of ursodeoxycholate in bile-induced pancreatic ductal injury. / Katona, M.; Hegyi, P.; Kui, Balázs; Balla, Zsolt; Rakonczay, Z.; Rázga, Zsolt; Tiszlavicz, L.; Maléth, József; Venglovecz, V.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 310, No. 3, 2016, p. G193-G204.

Research output: Contribution to journalArticle

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