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

Analytical strategies to assess the functional metabolome of vitamin E

“…Amperometric or coulometric ECD detectors are electively used to measure vitamin E metabolites such as NGT and quinone derivatives in biological samples that are poorly fluorescent and also present at very low concentrations to be assessed by UV detection; coulometric detection of these compounds can be achieved at sensitivity levels down to few picograms. In some cases, postcolumn reduction procedures are coupled with ECD detection [121,122] to measure oxidation products such as tocopheryl quinone, a method successfully applied to LCMs analysis in human plasma [40] as well as ␣-T/␣-TQ ratio in rat plasma [123] and human red blood cells [105]. HPLC-ECD has been successfully used to assess CEHCs in human urine [114] and plasma [59] and NGT formation in rats [117] and human plasma [10].…”

“…Accordingly, such a constitutive selectivity of capture and tissue transferring mechanisms in liver cells has been demonstrated to have important functional implications limiting the systemic bioavailability of non-␣-forms. In fact, human high-dose supplementation protocols based on the sole administration of ␣-T cause a massive depletion of blood ␥-T by stimulating its enzymatic metabolism [7,40,41], a condition that may cause health harms for instance by limiting the capability of scavenging NO-derived species in smokers [41] or in other groups at risk of developing nitrosative stress such as chronic kidney disease patients [42] and others as reviewed in [7].…”

“…Long-chain carboxychromanols can inhibit cyclooxygenase-2-catalyzed prostaglandin E 2 synthesis in Interleukin-1 ␤-stimulated A549 cells, and in vitamin E supplemented cells that effect was partially antagonized by the treatment with sesamin, a plant inhibitor of vitamin E metabolism effects [67]. ␣-13 -(6-hydroxy-2,5,7,8,-tetramethylchroman-2-yl)-2,6,10-trimethyltridecanol metabolite (␣-13 -OH) has been recently described to act as an in vitro modulator of key inflammatory pathways in macrophages [40]. In vitro anti-inflammatory and anti-atherogenic properties have also been described for the corresponding acid metabolite tentatively identified in human serum [47], namely ␣-13 -(6-hydroxy-2,5,7,8,-tetramethylchroman-2-yl)-2,6,10-trimethyltridecanoicacid (␣-13 -COOH) [68,69].…”

“…The lipophilic nature of long-chain chromanols hinders the possibility that these would be excreted to a significant extent in urine, therefore these can be measured in feces, cells and tissues [23], which obviously include blood as the elective sample to assess these metabolites in human nutrition and clinical studies [40,47]. Strategies of extraction for these compounds should be planned considering their lipophilic properties and the occurrence of an extensive sulfate derivatization for the acid forms [66].…”

“…More recently, the ␣-13 -OH metabolite has been measured by GC-MS analysis in human serum after ␣-T supplementation [40]. That analytical procedure was not sensitive enough to produce a quantitative measure of serum ␣-13 -COOH even after supplementation.…”