Indomethacin disrupts the protective effect of phosphatidylcholine against bile salt-induced ileal mucosa injury.
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).


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.
Venneman
N G
NG
Department of Gastro-enterology and Surgery, University Medical Center, Utrecht, the Netherlands.
Petruzzelli
M
M
van Dijk
J E
JE
Verheem
A
A
Akkermans
L M A
LM
Kroese
A B A
AB
van Erpecum
K J
KJ
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D018938:Caco-2 Cells; D002756:Cholagogues and Choleretics / Q000378:metabolism; D005260:Female; D006801:Humans; D007082:Ileum / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D007213:Indomethacin / Q000009:adverse effects*; D007413:Intestinal Mucosa / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D010539:Permeability; D010713:Phosphatidylcholines / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013657:Taurodeoxycholic Acid / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002756:Cholagogues and Choleretics; D010713:Phosphatidylcholines; D013657:Taurodeoxycholic Acid; D007770:L-Lactate Dehydrogenase; D007213:Indomethacin