Polymeric Binders Block Gliadin-induced Intestinal Cell Toxicity
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The team neutralized gliadin through complexation to a linear copolymer of hydroxyethylmethacrylate (HEMA) and sodium 4-styrene sulfonate (SS). They then examined the ability of the polymeric binder to mitigate the damaging effect of gliadin on cell-cell contact in IEC-6, Caco-2/15, and primary cultured differentiated enterocytes.
They used gliadin-sensitive HLA-HCD4/DQ8 transgenic mice to measure the effectiveness of the polymeric binder in averting gliadin-triggered intestinal barrier dysfunction. They found that Poly(hydroxyethylmethacrylate-co-styrene sulfonate) [P(HEMA-co-SS)] complexed with gliadin in a fairly precise manner.
Exposing intestinal cells to gliadin caused major changes in both cell structure and cell to cell contacts. By complexing the gliadin with P(HEMA-co-SS) the researchers were able to prevent these undesirable changes. More importantly, the P(HEMA-co-SS) inhibited gliadin digestion by gastrointestinal enzymes, which minimized the development of peptides that trigger immune adverse immune reactions.
By co-administering P(HEMA-co-SS) with gliadin to HLA-HCD4/DQ8 mice, researchers were able to eliminate gliadin-triggered changes in the gut barrier and lower intraepithelial lymphocyte and macrophage cell counts.
From these results, the team concludes that polymeric binders can prevent in vitro gliadin-induced epithelial toxicity and intestinal barrier dysfunction in HCD4/DQ8 mice. Such polymeric binders might play a significant role in the treating people with gluten-induced disorders.
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