Biokinetics of and discrimination between dietaryRRR‐ andSRR‐α‐tocopherols in the male rat

Abstract

The net rates of uptake of the natural (2R,4'R,8'R) diastereoisomer of alpha-tocopherol (alpha-T) and the biodiscrimination relative to its 2S-epimer (2S,4'R,8'R) have been measured, in two experiments, for the blood and 21 tissues of male Sprague-Dawley rats fed over a period of several months diets containing deuterium-substituted forms of the alpha-T acetates. Gas chromatography-mass spectrometry was used to measure the amount of deuterated tocopherols taken up relative to the amount of nondeuterated tocopherol remaining. The measurements were performed at different times after the rats, placed for one month on a basal diet containing nondeuterated, natural alpha-T acetate, were switched to a diet containing the same total quantity of deuterated forms of either natural alpha-T acetate or a mixture of the acetates of the 2R- and 2S-epimers (i.e., ambo-alpha-T acetate). In experiment 1 the source of vitamin E in the replacement diet was trideuterio-2R,4'R,8'R-alpha-T acetate. The data obtained provide the first direct measure of the rate at which natural vitamin E is replaced and augmented in the tissues of growing animals under normal laboratory dietary conditions. There are dramatic differences in the tissue kinetics; for example, the apparent half-life of vitamin E, i.e., the time at which the total amount of ingested trideuterio-alpha-T taken up is the same as the amount of nondeuterated alpha-T remaining, varies from ca. 1 wk for the lung to ca. 11 wk for the spinal cord. In experiment 2 the vitamin E in the replacement diet was an equimolar mixture of trideuterio-2S,4'R,8'R- and hexadeuterio-2R,4'R,8'R-alpha-T acetates. The results show that there is a preferential uptake of the natural diastereoisomer of alpha-T by all tissues (except the liver during the first month). Examination of fecal material reveals that the biodiscrimination begins in the gut; the incomplete hydrolysis of the acetates shows clearly that this reaction proceeds to a greater extent with the natural diastereoisomer. The greatest discrimination of all the tissues examined was found to occur in the brain. After five months, the level of the deuterated natural diastereoisomer was more than five times that of the deuterated 2S-epimer. These results have potential implications for human nutrition.

Molecular mechanisms of the protective role of wheat germ oil against cyclosporin A-induced hepatotoxicity in rats

“…Interestingly, the immunosuppressive effect of CsA was not altered by WGO. Previously, it has been reported that synthetic vitamin E does not have the same biological activity of natural vitamin E (Ingold et al, 1987;Pfluger et al, 2004). The richest known natural dietary source of vitamin E is WGO (Shurpalekar & Rao, 1977).…”

Intestinal expression of human apolipoprotein A-IV in transgenic mice fails to influence dietary lipid absorption or feeding behavior.

“…In humans (61)(62)(63), monkeys (64) and rats (65), RRRa-tocopherol is preferentially transported in plasma. Studies using perfused monkey livers demonstrated that RRR-atocopherol is preferentially secreted in nascent VLDL (54).…”

Isolation of tocopherol‐binding proteins from the cytosol of smooth muscle A7r5 cells

“…A cytosolic a-tocopherol-binding protein, also able to interact with other tocopherols, of apparent molecular mass 30.5 kDa, has been isolated from rat liver [20, 211. In mammals, a-tocopherol is secreted from liver associated with nascent very-low-density lipoproteins [23] and is carried in blood primarily by low-density and high-density lipoproteins [23,241. Experiments on a-tocopherol stereoisomer kinetics and uptake in different tissues revealed differences, with an especially high discrimination in gut and in brain [25].…”