Isolation and Identification of α-CEHC Sulfate in Rat Urine and an Improved Method for the Determination of Conjugated α-CEHC

Li, Yi-Jen; Luo, Sheng-Ching; Lee, Yi-Jing; Lin, Fei-Jan; Cheng, Chi‐Cheng; Wein, Yung-Shung; Kuo, Yueh‐Hsiung; Huang, Ching-jang

doi:10.1021/jf802459d

Cited by 29 publications

(18 citation statements)

References 27 publications

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“…Plasma samples (100 mL) were mixed with 1% ascorbic acid (100 mL) and b-glucuronidase (100 mL of 10 mg/L in 10 mmol/L acetate buffer; pH 6.8), incubated for 1 h at 378C, and subsequently cooled to room temperature. Urine samples (100 mL) were mixed with 500 mL 6N HCl (26), incubated for 1 h at 378C, and subsequently cooled to room temperature. Plasma or urine unconjugated catabolites were extracted with 4 mL diethyl ether, and an aliquot of the ether fraction was collected and dried under nitrogen.…”

Section: Measurements Of Plasma and Urinary Carboxyethyl Hydroxychrommentioning

confidence: 99%

Metabolic syndrome increases dietary α-tocopherol requirements as assessed using urinary and plasma vitamin E catabolites: a double-blind, crossover clinical trial

Traber

Mah

Leonard

et al. 2017

The American Journal of Clinical Nutrition

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Background: Vitamin E supplementation improves liver histology in patients with nonalcoholic steatohepatitis, which is a manifestation of the metabolic syndrome (MetS). We reported previously that a-tocopherol bioavailability in healthy adults is higher than in those with MetS, thereby suggesting that the latter group has increased requirements. Objective: We hypothesized that a-tocopherol catabolites a-carboxyethyl hydroxychromanol (a-CEHC) and a-carboxymethylbutyl hydroxychromanol (a-CMBHC) are useful biomarkers of a-tocopherol status. Design: Adults (healthy or with MetS; n = 10/group) completed a double-blind, crossover clinical trial with four 72-h interventions during which they co-ingested 15 mg hexadeuterium-labeled RRR-a-tocopherol (d 6 -a-T) with nonfat, reduced-fat, whole, or soy milk. During each intervention, we measured a-CEHC and a-CMBHC excretions in three 8-h urine collections (0-24 h) and plasma a-tocopherol, a-CEHC, and a-CMBHC concentrations at various times #72 h. Results: During the first 24 h, participants with MetS compared with healthy adults excreted 41% less a-CEHC (all values are leastsquares means 6 SEMs: 0.6 6 0.1 compared with 1.0 6 0.1 mmol/g creatinine, respectively; P = 0.002), 63% less hexadeuterium-labeled (d 6 )-a-CEHC (0.04 6 0.02 compared with 0.13 6 0.02 mmol/g creatinine, respectively; P = 0.002), and 58% less d 6 -a-CMBHC (0.017 6 0.004 compared with 0.041 6 0.004 mmol/g creatinine, respectively; P = 0.0009) and had 52% lower plasma d 6 -a-CEHC areas under the concentration curves [area under the curve from 0 to 24 h (AUC 0-24h ): 27.7 6 7.9 compared with 58.4 6 7.9 nmol/L 3 h, respectively; P = 0.01]. d 6 -a-CEHC peaked before d 6 -a-T in 77 of 80 paired plasma concentration curves. Urinary d 6 -a-CEHC 24-h concentrations were associated with the plasma AUC 0-24 h of d 6 -a-T (r = 0.53, P = 0.02) and d 6 -a-CEHC (r = 0.72, P = 0.0003), and with urinary d 6 -a-CMBHC (r = 0.88, P , 0.0001), and inversely with the plasma inflammation biomarkers C-reactive protein (r = 20.70, P = 0.0006), interleukin-10 (r = 20.59, P = 0.007), and interleukin-6 (r = 20.54, P = 0.01). Conclusion: Urinary a-CEHC and a-CMBHC are useful biomarkers to noninvasively assess a-tocopherol adequacy, especially in populations with MetS-associated hepatic dysfunction that likely impairs a-tocopherol trafficking. This trial was registered at clinicaltrials.gov as NCT01787591.Am J Clin Nutr 2017;105:571-9.

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Section: Measurements Of Plasma and Urinary Carboxyethyl Hydroxychrommentioning

confidence: 99%

Metabolic syndrome increases dietary α-tocopherol requirements as assessed using urinary and plasma vitamin E catabolites: a double-blind, crossover clinical trial

Traber

Mah

Leonard

et al. 2017

The American Journal of Clinical Nutrition

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“…Nearly 60 years ago, Simon et al ( 108 ) described vitamin E metabolism and its oxidized product "Simon metabolites" or ␣ -tocopheronolactone ( 107 ). Simon metabolites were thought to occur as a result of in vitro oxidation ( 109 ); they are decreased if an antioxidant is present during sample preparation ( 110 ). However, they have been found in increased concentrations in urine from diabetic subjects ( 111 ).…”

Section: ␣ -Tocopherol and Non-␣ -Tocopherol Metabolismmentioning

confidence: 99%

Mechanisms for the prevention of vitamin E excess

Traber

2013

Journal of Lipid Research

116

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“…Therefore, it is important to determine whether vitamin E undergoes catabolism in the small intestine, and whether its catabolism during absorption influences the bioavailability of dietary vitamin E. In the present study, we determined the CEHC content in various tissues, including the small intestine, in rats orally administered with vitamin E isoforms. We measured the total amounts of conjugated and unconjugated CEHC by methylation with methanolic HCl followed by HPLC analysis because the hydrolysis of sulfate-conjugated CEHC efficiently released free CEHC from rat samples ( 19 ). An analog of CEHC, 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (trolox), was used as an internal standard, as previously reported ( 15 ).…”

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confidence: 99%

Tissue Distribution of Vitamin E Metabolites in Rats after Oral Administration of Tocopherol or Tocotrienol

Uchida

Nomura

Ichikawa

et al. 2011

J Nutr Sci Vitaminol

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SummaryWe previously found that 2,7,8-trimethyl-2(2 ′ -carboxyethyl)-6-hydroxychroman ( ␥ CEHC), a metabolite of the vitamin E isoforms ␥ -tocopherol or ␥ -tocotrienol, accumulated in the rat small intestine. The aim of this study was to evaluate tissue distribution of vitamin E metabolites. A single dose of ␣ -tocopherol, ␥ -tocopherol or a tocotrienol mixture containing ␣ -and ␥ -tocotrienol was orally administered to rats. Total amounts of conjugated and unconjugated metabolites in the tissues were measured by HPLC with an electrochemical detector, and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (trolox) was used as an internal standard. Twenty-four hours later, the vitamin E isoforms were detected in most tissues and in the serum. However, 2,5,7,8-tetramethyl-2(2 ′ -carboxyethyl)-6-hydroxychroman ( ␣ CEHC), a metabolite of ␣ -tocopherol or ␣ -tocotrienol, and ␥ CEHC accumulated in the serum and in some tissues including the liver, small intestine and kidney. Administration of ␣ -tocopherol increased the ␥ CEHC concentration in the small intestine, suggesting that ␣ -tocopherol enhances ␥ -tocopherol catabolism. In contrast, ketoconazole, an inhibitor of cytochrome P450 (CYP)-dependent vitamin E catabolism, markedly decreased the ␥ CEHC concentration. These data indicate that vitamin E metabolite accumulates not only in the liver but also in the small intestine and kidney. We conclude that some dietary vitamin E is catabolized to carboxyethyl-hydroxychroman in the small intestine and is secreted into the circulatory system. Key Words carboxyethyl-hydroxychroman, tocopherol, tocotrienol, vitamin E Vitamin E is a fat-soluble antioxidant that inhibits lipid peroxidation in biological membranes. In nature, compounds with vitamin E activity are ␣ -, ␤ -, ␥ -or ␦ -tocopherol and ␣ -, ␤ -, ␥ -or ␦ -tocotrienol. ␣ -and ␥ -tocopherol are abundant in dietary vitamin E while tocotrienol is only present in some plant sources, such as palm oil and rice bran, while daily foods contain low levels of tocotrienol. The dietary vitamin E isoforms are absorbed in the small intestine, secreted with triacylglycerol-rich chylomicrons into the lymph and blood, and then transported to the liver ( 1 , 2 ). The vitamin E isoform ␣ -tocopherol is preferentially incorporated into VLDL and transported to tissues by lipoprotein ( 3 , 4 ) because of its high affinity for ␣ -tocopherol transfer protein ( ␣ TTP) ( 5 ). In contrast, the other vitamin E isoforms, including ␥ -tocopherol and tocotrienol, are catabolized and excreted. Therefore, ␣ -tocopherol has the highest biological activity among vitamin E isoforms.All vitamin E isoforms undergo catabolism to phytyl short-chain carboxyethyl hydroxychromans (CEHC) such as 2,5,7,8-tetramethyl-2(2 ′ -carboxyethyl)-6-hydroxychroman ( ␣ CEHC), a metabolite of ␣ -tocopherol and ␣ -tocotrienol, and 2,7,8-trimethyl-2(2 ′ -carboxyethyl)-6-hydroxychroman ( ␥ CEHC), a metabolite of ␥ -tocopherol and ␥ -tocotrienol ( 6-8 ). The catabolic pathway involves -hydroxylation of the phytyl chain and ...

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Isolation and Identification of α-CEHC Sulfate in Rat Urine and an Improved Method for the Determination of Conjugated α-CEHC

Cited by 29 publications

References 27 publications

Metabolic syndrome increases dietary α-tocopherol requirements as assessed using urinary and plasma vitamin E catabolites: a double-blind, crossover clinical trial

Metabolic syndrome increases dietary α-tocopherol requirements as assessed using urinary and plasma vitamin E catabolites: a double-blind, crossover clinical trial

Mechanisms for the prevention of vitamin E excess

Tissue Distribution of Vitamin E Metabolites in Rats after Oral Administration of Tocopherol or Tocotrienol

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