Limited information is available regarding metabolism of vitamin E forms, especially the tocotrienols. Carboxyethyl-hydroxychromans (alpha- and gamma-CEHC) are human urinary metabolites of alpha- and gamma-tocopherols, respectively. To evaluate whether tocotrienols are also metabolized and excreted as urinary CEHC, urine was monitored following tocotrienol supplementation. Complete (24 h) urine collections were obtained for 2 d prior to (baseline), the day of, and 2 d after human subjects (n = 6) ingested tocotrienol supplements. The subjects consumed 125 mg gamma-tocotrienyl acetate the first week, then the next week 500 mg; then 125 mg alpha-tocotrienyl acetate was administered the third week, followed by 500 mg the fourth week. Urinary alpha- and gamma-CEHC were measured by high-performance liquid chromatography with electrochemical detection. Urinary gamma-CEHC levels rose about four- to sixfold in response to the two doses of gamma-tocotrienol and then returned to baseline the following day. Significant (P < 0.0001) increases in urinary alpha-CEHC were observed only following ingestion of 500 mg alpha-tocotrienyl acetate. Typically, 1-2% of alpha-tocotrienyl acetates or 4-6% of gamma-tocotrienyl acetates were recovered as their respective urinary CEHC metabolites. A gamma-CEHC excretion time course showed an increase in urinary gamma-CEHC at 6 h and a peak at 9 h following ingestion of 125 mg gamma-tocotrienyl acetate. In summary, tocotrienols, like tocopherols, are metabolized to CEHC; however, the quantities excreted in human urine are small in relation to dose size.

Vitamin E supplementation could elevate circulating vitamin E metabolites while modulating oxidative and inflammatory status in end-stage renal failure patients undergoing hemodialysis. Plasma concentrations of carboxyethyl-hydroxychromanols (alpha- and gamma-CEHC), ascorbic acid, alpha- and gamma-tocopherols, F2-isoprostanes, and inflammatory biomarkers [tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), ferritin, and C-reactive protein (CRP)] were measured in blood samples obtained from patients (n = 11) before and after dialysis on two occasions prior to, and at 1 and 2 mon of daily vitamin E supplementation (400 IU RRR-alpha-tocopherol). Supplementation nearly doubled plasma alpha-tocopherol concentrations (from 18 +/- 0.5 to 31 +/- 1.7 microM, P < 0.0001), whereas gamma-tocopherol concentrations decreased (from 2.8 +/- 0.3 to 1.7 +/- 0.2 microM, P = 0.001). Serum alpha-CEHC increased 10-fold from 68 +/- 3 to 771 +/- 175 nM (P < 0.0001), and gamma-CEHC increased from 837 +/- 164 to 1136 +/- 230 nM (P = 0.008). Vitamin E supplementation also increased postdialysis hematocrits from 38 +/- 1% to 41 +/- 1% (P < 0.001). Dietary antioxidant intakes (vitamins E and C) were low in most subjects; plasma ascorbic acid levels (88 +/- 27 microM) decreased significantly with dialysis (33 +/- 11 microM, P = 0.01). Plasma IL-6, CRP, TNF-alpha, and free F2-isoprostane concentrations were elevated throughout the study. There is a complex relationship between chronic inflammation and oxidative stress that is not mitigated by short-term vitamin E supplementation. Importantly, serum vitamin E metabolite concentrations that increased 10-fold within 30 d of supplementation did not increase further, suggesting routes other than urine for removal of metabolites.

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JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship. For more information about JSTOR, please contact support@jstor.org.. The National Institute of Environmental Health Sciences (NIEHS) and Brogan & Partners are collaborating with JSTOR to digitize, preserve and extend access to Environmental Health Perspectives.Circulating cadmium-thionein (Cd-MT) is cleared from the mammalian circulatory system by filtration through the kidney glomerulus with subsequent reabsorption by kidney proximal tubules. Damage to the tubules results following uptake of Cd-MT, which is dependent upon time and the dose level of cadmium administered. Intravenous administration of 109Cd-MT at doses of 0.017 and 0.17 mg Cd/kg body weight with examination of total renal uptake of '09Cd at 0.5, 3, and 24 hr disclosed that the rate of clearance from the blood and uptake by the kidney was significantly more rapid at the 0.017 mg Cd/kg dose. Ultrastructural changes resulting from intravenous injection of either form A or B of Cd-MT were characterized by increased numbers of pinocytotic vesicles and small, dense lysosomal structures. There was no evidence of mitochondrial swelling or cell death at either 3 or 6 hr after injection. The subcellular distribution of cadmium in kidney tissue at various times after administration of Cd-MT was determined by using differential centrifugation techniques with "*"Cd and in situ by using x-ray microanalysis. At 30 min after injection of Cd-MT, significant amounts of cadmium were present in lysosomal fractions indicating an interaction between the tubular lysosome system and Cd-MT prior to the onset of overt cellular toxicity. Results suggest that Cd-MT is reabsorbed and broken down by kidney tubule cells in a physiological manner with possible subsequent release of the toxic cadmium ion.

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