Indomethacin enhances bile salt detergent activity: relevance for NSAIDs-induced gastrointestinal mucosal injury.

Digestive Diseases and Sciences
M PetruzzelliKarel J van Erpecum

Abstract

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 ...Continue Reading

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Citations

Dec 19, 2007·Journal of Gastroenterology and Hepatology·Elizabeth J DialLenard M Lichtenberger
Mar 6, 2010·American Journal of Physiology. Gastrointestinal and Liver Physiology·Yong ZhouLenard M Lichtenberger
May 18, 2011·Evidence-based Complementary and Alternative Medicine : ECAM·Hironori Ishikawa, Shiro Watanabe
May 15, 2007·Life Sciences·Emily K Y LamC H Cho
Feb 27, 2007·Clinical Biochemistry·Michele PetruzzelliPiero Portincasa
Aug 14, 2012·Biochimica Et Biophysica Acta·Priyanka PrakashAlemayehu A Gorfe
Jul 3, 2010·Biochimica Et Biophysica Acta·Robert EhehaltWolfgang Stremmel
Dec 1, 2014·Medical Hypotheses·C M SpiesF Buttgereit
Oct 2, 2007·Current Opinion in Gastroenterology·Maggie Ham, Jonathan D Kaunitz
Dec 6, 2014·American Journal of Physiology. Gastrointestinal and Liver Physiology·Elizabeth J DialLenard M Lichtenberger
Mar 31, 2021·Journal of Gastroenterology and Hepatology·Naoki ShibuyaRyota Hokari

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