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

• Main Authors: Vladana Domazetovic (Author), Irene Falsetti (Author), Caterina Viglianisi (Author), Kristian Vasa (Author), Cinzia Aurilia (Author), Maria Stio (Author), Stefano Menichetti (Author), Teresa Iantomasi (Author)
• Format: Book
• Published: MDPI AG, 2021-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/antiox10020160; 2076-3921
• Keywords: oxidative stress; natural and semi-synthetic tocopherols; tumor necrosis factor-α (TNFα); intercellular adhesion molecule-1 (ICAM-1); claudin-2 (Cl-2); Therapeutics. Pharmacology; RM1-950
• Source: Antioxidants, Vol 10, Iss 2, p 160 (2021)

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, <b>α-Toc</b> and <b>δ-Toc</b>, and two semi-synthetic derivatives, namely <i>bis</i>-δ-Toc sulfide <b>(δ-Toc)₂S</b> and <i>bis</i>-δ-Toc disulfide <b>(δ-Toc)₂S₂</b>, on TNFα-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 <i>N</i>-acetylcysteine (NAC), an antioxidant precursor of glutathione synthesis. The results show that all tocopherol containing derivatives used, prevented TNFα-induced oxidative stress and the increase of ICAM-1 and Cl-2 expression, and that <b>(δ-Toc)₂S</b> and <b>(δ-Toc)₂S</b>₂ are more effective than <b>δ-Toc</b> and <b>α-Toc</b>. The beneficial effects demonstrated were due to tocopherol antioxidant properties, but suppression of TNFα-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 TNFα-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 TNFα represents an important proinflammatory mediator.