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

Abstract

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 ...

Tissue Distribution of α‐ and γ‐Tocotrienol and γ‐Tocopherol in Rats and Interference with Their Accumulation by α‐Tocopherol

“…CEHC is then conjugated with glucuronate in humans or with sulfate in rats and subsequently excreted in the urine. Vitamin E metabolites are found in the liver, kidneys, small intestine, and serum of rats after oral administration of tocopherol or tocotrienol [36].…”

“…Ketoconazole also increased c-tocopherol concentrations in rat tissues by inhibiting its catabolism to c-CEHC, suggesting that CYP-dependent catabolism of vitamin E is a critical determinant of its bioavailability. Some reports indicate that a-tocopherol enhances c-tocopherol catabolism to c-CEHC [35,36,39]. In contrast, dietary a-tocopherol does not affect urinary excretion of c-CEHC in rats fed a diet containing c-tocotrienol for 8 weeks [19].…”

Neuroprotective Effects of α-Tocotrienol on Kainic Acid-Induced Neurotoxicity in Organotypic Hippocampal Slice Cultures

“…Vitamin E is a chain-breaking antioxidant; it is able to repair oxidizing radicals directly, preventing the chain propagation step during lipid peroxidation [7]. In the vitamin E group, alpha-tocopherol (ATPH) and alpha-tocotrienol (ATTN) are suggested to have the highest biological activity [8,9]. However, the functions of tocotrienols have not been fully elucidated.…”

Mechanisms for the prevention of vitamin E excess

“…In rats, accumulation of ␣ -tocotrienol in various organs could be demonstrated when large quantities of ␣ -tocotrienol were administered by gavage for more than two years; when ␣ -tocotrienol administration was stopped and the diet was replaced with a vitamin E-defi cient diet, ␣ -tocotrienol depletion took less than two months, while loss of ␣ -tocopherol was negligible ( 117 ). Uchida et al ( 118,119 ) showed that ␣ -tocopherol stimulated the disappearance of non-␣ -tocopherol and increased CEHC production. It is likely that metabolism of the tocotrienols observed in rats led to its rapid disappearance, as faster turnover of tocotrienols has also been seen in humans ( 120 ).…”