Protective Role of Natural and Semi-Synthetic Tocopherols on TNFα-Induced ROS Production and ICAM-1 and Cl-2 Expression in HT29 Intestinal Epithelial Cells

Vitamin E, a fat-soluble compound, possesses both antioxidant and non-antioxidant properties. In this study we evaluated, in intestinal HT29 cells, the role of natural tocopherols, alpha-Toc and delta-Toc, and two semi-synthetic derivatives, namely bis-delta-Toc sulfide (delta-Toc)(2)S and bis-delta-Toc disulfide (delta-Toc)(2)S-2, on TNF alpha-induced oxidative stress, and intercellular adhesion molecule-1 (ICAM-1) and claudin-2 (Cl-2) expression. The role of tocopherols was compared to that of N-acetylcysteine (NAC), an antioxidant precursor of glutathione synthesis. The results show that all tocopherol containing derivatives used, prevented TNF alpha-induced oxidative stress and the increase of ICAM-1 and Cl-2 expression, and that (delta-Toc)(2)S and (delta-Toc)(2)S-2 are more effective than delta-Toc and alpha-Toc. The beneficial effects demonstrated were due to tocopherol antioxidant properties, but suppression of TNF alpha-induced Cl-2 expression seems not only to be related with antioxidant ability. Indeed, while ICAM-1 expression is strongly related to the intracellular redox state, Cl-2 expression is TNF alpha-up-regulated by both redox and non-redox dependent mechanisms. Since ICAM-1 and Cl-2 increase intestinal bowel diseases, and cause excessive recruitment of immune cells and alteration of the intestinal barrier, natural and, above all, semi-synthetic tocopherols may have a potential role as a therapeutic support against intestinal chronic inflammation, in which TNF alpha represents an important proinflammatory mediator.

Automated summary

The study found that tocopherol derivatives can prevent TNFα-induced oxidative stress and inhibit the increase of ICAM-1 and Cl-2 expression. Among them, (δ-Toc)2S and (δ-Toc)2S-2 were more effective than δ-Toc and α-Toc.