Izsum.it (C.B.); [email protected] (F.P.) Division of Chemistry, Biology and Biotechnology, University of Perugia, 06126 Perugia, Italy; [email protected] Division of Biomolecular Sciences, University of Urbino “Carlo Bo”, 61029 Urbino, Italy; [email protected] Correspondence: [email protected]; Tel.: +39-075-585-7445 Equal contribution.Citation: Bartolini, D.e; Marinelli, R.; Giusepponi, D.; Galarini, R.; Barola, C.; Stabile, A.M.; Sebastiani, B.; Paoletti, F.; Betti, M.; Rende, M.; et al. Alpha-Tocopherol Metabolites (The Mcl-1 Inhibitor drug vitamin E Metabolome) and Their Interindividual Variability through Supplementation. Antioxidants 2021, ten, 173. https://doi.org/10.3390/ antiox10020173 Received: 9 December 2020 Accepted: 20 January 2021 Published: 25 JanuaryPublisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.Abstract: The metabolism of -tocopherol (-TOH, vitamin E) shows marked interindividual variability, which may possibly influence the response to nutritional and therapeutic interventions with this vitamin. Not too long ago, new metabolomics protocols have fostered the possibility to explore such variability for the various metabolites of -TOH so far identified in human blood, i.e., the “vitamin E metabolome”, a number of which have already been reported to promote significant biological functions. Such advances prompt the definition of reference values and Tyk2 Inhibitor medchemexpress degree of interindividual variability for these metabolites at different levels of -TOH intake. To this finish, a one-week oral administration protocol with 800 U RRR–TOH/day was performed in 17 healthy volunteers, and -TOH metabolites had been measured in plasma before and in the finish on the intervention using a lately validated LC-MS/MS procedure; the expression of two target genes of -TOH with doable a part in the metabolism and function of this vitamin, namely pregnane X receptor (PXR) and the isoform 4F2 of cytochrome P450 (CYP4F2) was assessed by immunoblot in peripheral blood leukocytes. The levels of enzymatic metabolites showed marked interindividual variability that characteristically elevated upon supplementation. With all the exception of -CEHC (carboxy-ethyl-hydroxychroman) plus the long-chain metabolites M1 and -13 OH, such variability was found to interfere with the possibility to utilize them as sensitive indicators of -TOH intake. Around the contrary, the cost-free radical-derived metabolite -tocopheryl quinone significantly correlated with the post-supplementation levels of -TOH. The supplementation stimulated PXR, but not CYP4F2, expression of leucocytes, and important correlations have been observed in between the baseline levels of -TOH and both the baseline and post-supplementation levels of PXR. These findings offer original analytical and molecular information and facts with regards to the human metabolism of -TOH and its intrinsic variability, which can be worth taking into consideration in future nutrigenomics and interventions research. Keywords and phrases: -tocopherol; vitamin E; metabolomics; nutrigenomics; pregnane X receptor; lipoxygenase5; peroxisome proliferator-activated receptor-; mass spectrometry; interindividual variabilityCopyright: 2021 by the authors. Licensee MDPI, Basel, Switzerland. This short article is definitely an open access article distributed below the terms and circumstances of your Inventive Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ four.0/).1. Introduction The term vitamin E refers towards the essential micronutrient -tocophe.
