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Indomethacin disrupts the protective effect of phosphatidylcholine against bile salt‐induced ileal mucosa injury
Author(s) -
Venneman N. G.,
Petruzzelli M.,
Dijk J. E.,
Verheem A.,
Akkermans L. M. A.,
Kroese A. B. A.,
Erpecum K. J.
Publication year - 2006
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.2006.01595.x
Subject(s) - chemistry , ussing chamber , intestinal mucosa , incubation , phosphatidylcholine , caco 2 , pharmacology , permeability (electromagnetism) , in vitro , medicine , biochemistry , phospholipid , membrane
Background Indomethacin (Indo) exerts local toxic effects on small intestinal mucosa, possibly in association with hydrophobic bile salts. We investigated the potential toxic effects of Indo on ileal mucosa and the role of phosphatidylcholine (PC). Materials and methods Transmucosal resistance and Na‐fluorescein permeability of ileal mucosa segments from female Wistar rats were determined in Ussing chambers during a 30‐min incubation with model systems containing: control‐buffer, taurodeoxycholate (TDC), Indo, TDC‐Indo, TDC‐PC, or TDC‐PC‐Indo. Decrease of resistance and increase of permeability were considered as parameters for mucosal injury. After incubation in Ussing chambers, the histopathology was examined to quantify the extent of mucosal injury. Also, in CaCo‐2 cells, LDH‐release was determined as a measure of cytotoxicity, after incubation with various model systems. Results Decrease of resistance and increase of permeability were highest in systems containing TDC‐Indo ( P < 0·01). Phosphatidylcholine protected against the cytotoxic effects of TDC in absence of Indo only. Extent of mucosal injury by histological examination was also highest in systems containing TDC‐Indo ( P = 0·006). Again, PC exhibited protective effects in absence of Indo only. The LDH‐release by CaCo2‐cells was strongest in TDC‐Indo systems ( P < 0·001). Conclusions Indomethacin disrupts protective effects of PC against bile salt‐induced ileal mucosa injury. This finding is relevant for small intestinal injury induced by non‐steroidal anti‐inflammatory drugs.