Involvement of gliadin, a component of wheat gluten, in increased intestinal permeability leading to non-steroidal anti-inflammatory drug-induced small-intestinal damage (1)
25% of patients with rheumatoid arthritis who took NSAIDs for more than 3 months had mild small-intestinal damage, and more important, 27.8% of patients had severe damage and decreased hemoglobin levels. In gastrointestinal tract, NSAIDs interact with phospholipids of cellular membrane and intracellular mitochondrial oxidative phosphorylation, which initiates biochemical changes that impair function of the mucosal barrier, which results in increase in intestinal permeability. Gliadin may have a role in a variety of diseases, such as type 1 diabetes, rheumatoid arthritis, primary Sjögren’s syndrome, and multiple sclerosis.
Fractionation of the gliadin yielded staining bands with molecular weights mainly between 30 and 42 kDa, which correspond to α/β- and γ-gliadins. High molecular weight fractions, which represent ω-gliadin, were observed less than low molecular weight fractions.
In the GFD group, gliadin increased the lesion indices compared with those in vehicle-treated mice, and administration of gliadin increased the lesion indices in the GFD group in a dose-dependent manner. Gliadin increased the MPO activities of small-intestinal tissue in the GFD group administered with indomethacin.
Gliadin administration resulted in a 4.3-fold increase in intestinal paracellular permeability without the administration of indomethacin, and also increased the intestinal permeability in indomethacin-administered mice compared with that in vehicle-treated mice (2.1-fold).
The relative phosphorylation rate of EGFR in small-intestinal tissue after a single administration of gliadin increased 4 h later and disappeared after 24 h, and it was suppressed by the administration of erlotinib. FITC-dextran experiments with indomethacin administration, erlotinib attenuated paracellular permeability in the gliadin-administered group.
A particular gliadin peptide that accumulated in lysosomes induced oxidative stress in T84 and Caco-2 cell lines, and that increased permeability in response to an oxidant was related to EGFR phosphorylation.