Curcumin Ameliorates Hydrogen Peroxide-Induced Epithelial Barrier Disruption by Upregulating Heme Oxygenase-1 Expression in Human Intestinal Epithelial Cells

Disruption of epithelial tight junctions (TJ) followed by loss of barrier function is of crucial importance in the pathogenesis of a variety of gastrointestinal disorders. Heme oxygenase-1 (HO-1), which can be induced by curcumin (Cur), provides protection against various forms of oxidative stress. The protective effect of Cur on oxidative stress-induced intestinal barrier disruption in human intestinal epithelial cells was elucidated in this study. H2O2-induced Caco-2 enterocytic monolayers were incubated in the presence or absence of Cur and/or zinc protoporphyrin (ZnPP). The trans-epithelial electrical resistance (TEER) and the flux of sodium fluorescein in the filter-grown Caco-2 cell monolayers were measured. The expression and localization of the TJ protein occludin and zonula occluden-1 (ZO-1) were evaluated by western blot and immunofluorescence microscopy. The mRNA and protein levels of HO-1 were analyzed by real-time PCR and western blot. Cur attenuated H2O2-induced disruption of paracellular permeability (TEER 52.02 +/- A 10.15% vs 22.71 +/- A 3.11%; sodium fluorescein flux 12.41 +/- A 2.19% vs 32.00 +/- A 4.97%, P < 0.05) and induced HO-1 mRNA (6.64 +/- A 0.48 vs 3.22 +/- A 0.28, P < 0.05) and protein (291.00 +/- A 9.17% vs 99.00 +/- A 10.00%, P < 0.05) expression in Caco-2 cells. After administration of H2O2, occludin and ZO-1 proteins were restored by Cur (occludin 175.67 +/- A 29.50% vs 53.67 +/- A 24.19%, P < 0.05; ZO-1 139.67 +/- A 33.71% vs 36.00 +/- A 15.88%, P < 0.05) and this effect was blocked by HO-1 inhibitor, ZnPP (occludin 54.67 +/- A 10.02% vs 168.33 +/- A 36.47%, P < 0.05; ZO-1 50.00 +/- A 15.13% vs 117.67 +/- A 38.81%, P < 0.05). Cur protects human intestinal epithelial cells against H2O2-induced disruption of TJ and barrier dysfunction via the HO-1 pathway.