ESPEN 2012 - Late breaking abstract submission

Topic: Late Breaking Abstract

Abs n°:ESPEN12-1884

Abs Title: INDOMETHACIN-INDUCED TRANSLOCATION OF BACTERIA ACROSS ENTERIC EPITHELIA IS REACTIVE OXYGEN SPECIES-DEPENDENT AND REDUCED BY VITAMIN-C

I. Schoultz ^{1 2,*}C. M. McKay ²R. Graepel ²V. C. Phan ²A. Wang ²J. D. Söderholm ³D. M. McKay ²

¹The nutrition and physical activity research center, Örebro University, Örebro, Sweden, ²physiology and pharmacology, University of Calgary, Calgary, Canada, ³Clinical and Experimental Medicine, Linköping University, Linköping, Sweden

Rationale: Non-steroid anti-inflammatory drugs (NSAIDs), such as indomethacin and piroxicam, are associated with significant gastrointestinal side-effects. The exact mechanism behind the NSAID-induced barrier dysfunction is still not completely understood. 

Methods: The effect of indomethacin, piroxicam (cyclooxygenase 1 and 2 inhibitors) and the SC-560 (COX-1 inhibitor) was investigated on the barrier function of human T84 epithelial cell line monolayers by transepithelial electrical resistance (TER), internalization and translocation of a commensal Escherichia coli. The involvement of reactive oxygen species (ROS) was tested by inclusion of the known ROS scavengers in the cell culture medium: vitamin C (0.25mM) and the green tea extract epigallocatechin gallate (EGCG; 0.1mM). The ROS was determined by the fluorescent probes CM-H₂DCFDA and MitoSOX.

Results: Exposure to E. coli ± drugs for 16h reduced TER. Monolayers co-treated with E. coli+indomethacin, but not piroxicam or SC-560, showed significant increases in internalization and translocation of the bacteria.  This was accompanied by increased reactive oxygen species (ROS) production, which was also increased in E. coli–only treated epithelia. Colocalization revealed up-regulation of superoxide synthesis by mitochondria in E. coli+indomethacin-treated epithelia. Vitamin C and EGCG, quenched the ROS and prevented the increase in E. coli internalization and translocation evoked by indomethacin, but not the drop in TER.  Evidence of increased apoptosis was not observed in this model system. 

Conclusion: The data implicate epithelial-derived ROS in indomethacin-induced barrier dysfunction. We speculate that addition of antioxidants as dietary supplements to NSAID treatments would reduce the magnitude of decreased barrier function, specifically the transepithelial passage of bacteria. 

Disclosure of Interest: None Declared

Keywords: intestinal barrier functionNSAID