Intestinal mucosal damage caused by non-steroidal anti-inflammatory drugs: Role of bile salts

Michele Petruzzelli, Michele Vacca, Antonio Moschetta, Rosa Cinzia Sasso, Giuseppe Palasciano, Karel J. van Erpecum, Piero Portincasa

Research output: Contribution to journalReview article

32 Scopus citations

Abstract

The strong analgesic, anti-inflammatory effects of non-steroidal anti-inflammatory drugs (NSAIDs) are hampered by high occurrence of gastrointestinal side effects. Therapeutic actions of NSAIDs result from cyclooxygenase (COX) enzymes inhibition with reduced synthesis of prostaglandins, major modulators of inflammation. Since prostaglandins also regulate key events in gut homeostasis -mucosal secretion, blood flow, epithelial regeneration - COX inhibition has been accepted as the reason for NSAID gastrointestinal toxicity. Several findings challenge this theory: first, intestinal damage by NSAIDs occurs also in COX-1 knockout mice, demonstrating that topical (non-prostaglandin mediated) mechanisms are involved; second, no correlation is found in vivo between the extent of intestinal injury and the degree of inhibition of prostaglandin synthesis; third, bile flow interruption in animal models completely prevents intestinal damage by parenterally administered NSAIDs. What is in bile that could play a role in NSAID toxicity? This timely review will critically discuss the role of bile salts in NSAID-dependent gut damage.

Original languageEnglish (US)
Pages (from-to)503-510
Number of pages8
JournalClinical Biochemistry
Volume40
Issue number8
DOIs
StatePublished - May 1 2007

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Keywords

  • Bile salts
  • Cyclooxygenase (COX)
  • Farnesoid X Receptor
  • Intestinal toxicity
  • Non-steroidal anti-inflammatory drugs (NSAIDs)
  • Phospholipids

ASJC Scopus subject areas

  • Clinical Biochemistry

Cite this

Petruzzelli, M., Vacca, M., Moschetta, A., Cinzia Sasso, R., Palasciano, G., van Erpecum, K. J., & Portincasa, P. (2007). Intestinal mucosal damage caused by non-steroidal anti-inflammatory drugs: Role of bile salts. Clinical Biochemistry, 40(8), 503-510. https://doi.org/10.1016/j.clinbiochem.2007.01.015