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NSAIDs Ibuprofen, Indometacin, and Diclofenac do not interact with Farnesoid X Receptor

Jurema Schmidt1, Franca-Maria Klingler1, Ewgenji Proschak1

  • 1Institute of Pharmaceutical Chemistry, Goethe-University Frankfurt, Max-von-Laue-Str. 9, 60438 Frankfurt, Germany.

Scientific Reports
|October 2, 2015
PubMed

Insights

Non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen do not inhibit the farnesoid X receptor (FXR), a key liver protector. Reported hepatotoxic effects are a consequence, not a cause, of reduced FXR signaling.

Area of Science:

  • Hepatology
  • Pharmacology
  • Molecular Biology

Background:

  • The nuclear farnesoid X receptor (FXR) is a crucial liver protector sensing bile acids.
  • FXR inhibition or knockout leads to detrimental liver effects.
  • Recent studies suggested non-steroidal anti-inflammatory drugs (NSAIDs) antagonize FXR, potentially explaining their hepatotoxicity.

Purpose of the Study:

  • To investigate the proposed FXR antagonistic activity of NSAIDs.
  • To clarify the relationship between NSAIDs, FXR signaling, and drug-induced hepatotoxicity.

Main Methods:

  • In vitro characterization of ibuprofen, indometacin, and diclofenac interactions with FXR.
  • Assessment of FXR signaling in the presence of NSAIDs and chenodeoxycholic acid (CDCA).

Main Results:

  • The investigated NSAIDs (ibuprofen, indometacin, diclofenac) do not directly interact with or inhibit FXR.
  • Reduced FXR signaling observed with NSAIDs was found to be a consequence, not the cause, of hepatotoxicity.

Conclusions:

  • NSAIDs do not act as FXR antagonists.
  • The hepatotoxic effects of NSAIDs are not mediated by FXR antagonism.
  • This finding necessitates a re-evaluation of NSAID-induced liver injury mechanisms.

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