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

Abstract

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, α-Toc and δ-Toc, and two semi-synthetic derivatives, namely bis-δ-Toc sulfide (δ-Toc)2S and bis-δ-Toc disulfide (δ-Toc)2S2, 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 N-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 (δ-Toc)2S and (δ-Toc)2S2 are more effective than δ-Toc and α-Toc. 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.

Effects of daily functional acorn cake consumption on insulin resistance in individuals with obesity or overweight and the metabolic syndrome: a placebo-controlled randomised clinical trial

“…Besides, acorns are remarkable sources of tocopherols (α-and γ-tocopherol), which can reduce oxidative stress by accumulating in cell membranes (8,45) . Some researchers have indicated the role of tocopherols (α-and γ-tocopherol) in the modulation of inflammatory factors (46)(47)(48) . Therefore, the effects of FC on alleviating inflammatory markers can be described by its contents.…”

The Potential Role of Vitamin E and the Mechanism in the Prevention and Treatment of Inflammatory Bowel Disease

“…In HT29 cells, TNF-α can increase intracellular ROS production and promote the expression levels of ICAM-1 and Claudin-2, thereby changing intestinal epithelial barrier function and aggravating inflammation. Supplementation of α-tocotrienol and δ-tocotrienol (50 and 100 μM) could reduce the ROS content in a TNF-α-induced-inflammation model in vitro [ 109 ]. Based on these findings, the potential mechanism of vitamin E in the prevention and treatment of IBD is summarized in Figure 3 .…”

Vitamin E beyond Its Antioxidant Label

“…δ-TT also decreases the TNF-α-induced activation of NF-κB (via TAK1 and A20 signaling) and the LPS-stimulated expression of IL-6 in a time- and dose-dependent manner [ 72 ]. TFs were able to prevent TNF-α-induced oxidative stress, increasing ICAM-1 an Cl-2 expression in intestinal epithelial cells (via redox and non-redox mechanisms), while their sulfide and disulfide derivates were even more active [ 73 ]. However, in fetal-derived intestinal cells, TFs enhanced NF-κB and Nrf2 signaling after an IFN-γ/PMA challenge, possibly contributing to a pro-inflammatory response [ 74 ].…”