Human serum determination and in vitro anti-inflammatory activity of the vitamin E metabolite α-(13'-hydroxy)-6-hydroxychroman

Free Radic Biol Med. 2015 Dec:89:952-62. doi: 10.1016/j.freeradbiomed.2015.08.019. Epub 2015 Oct 8.

Abstract

Cytochrome P450-derived long-chain metabolites are gaining increasing interest as bioactive intermediates of vitamin E. In this study we first report on the HPLC-ECD and GC-MS analysis in human serum of the earliest metabolite of this vitamin, namely α-(13'-hydroxy)-6-hydroxychroman (α-13'-OH). The two chromatographic procedure are sensitive enough (LOQ of 10nM) to measure α-13'-OH after hexane extraction of 1 ml of sample obtained from healthy volunteers supplemented for 1-week with 1000 IU/d (671 mg/d) RRR-α-tocopherol. The observed concentrations ranged between 15 and 50 nM, with minor differences between fasting and 4-hr post-meal state. Baseline (non-supplemented state) levels of 7.2 ± 1.6 nM were observed extracting higher volumes of serum. Biological effects of α-13'-OH investigated for the first time in RAW264.7 murine macrophages involved transcriptional control of inflammatory cytokines, and transcriptional and functional regulation of COX2 and iNOS enzymes in response to lipopolysaccharides. In conclusion, here we present the first quantitative evaluation of serum α-13'-OH also providing early evidence of the anti-inflammatory potential of this metabolite that is worth of further investigation in the area of functional and nutraceutical implications of vitamin E metabolism.

Keywords: CYP4F2; Cytochrome P-450; Cytokines; Inflammation; Long-chain metabolites; Tocopherol; Vitamin E; α-13’-OH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Anti-Inflammatory Agents / blood*
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / pharmacology
  • Blotting, Western
  • Cells, Cultured
  • Cytokines / genetics
  • Cytokines / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • In Vitro Techniques
  • Inflammation Mediators
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Male
  • Mice
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tocopherols / blood*
  • Tocopherols / pharmacology*

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • Cytokines
  • Inflammation Mediators
  • RNA, Messenger
  • Tocopherols