Article

Regulatory mechanisms to control tissue α-tocopherol

Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA.
Free Radical Biology and Medicine (Impact Factor: 5.71). 09/2007; 43(4):610-8. DOI: 10.1016/j.freeradbiomed.2007.05.027
Source: PubMed

ABSTRACT To test the hypothesis that hepatic regulation of alpha-tocopherol metabolism would be sufficient to prevent overaccumulation of alpha-tocopherol in extrahepatic tissues and that administration of high doses of alpha-tocopherol would up-regulate extrahepatic xenobiotic pathways, rats received daily subcutaneous injections of either vehicle or 0.5, 1, 2, or 10 mg alpha-tocopherol/100 g body wt for 9 days. Liver alpha-tocopherol increased 15-fold in rats given 10 mg alpha-tocopherol/100 g body wt (mg/100 g) compared with controls. Hepatic alpha-tocopherol metabolites increased with increasing alpha-tocopherol doses, reaching 40-fold in rats given the highest dose. In rats injected with 10 mg/100 g, lung and duodenum alpha-tocopherol concentrations increased 3-fold, whereas alpha-tocopherol concentrations of other extrahepatic tissues increased 2-fold or less. With the exception of muscle, daily administration of less than 2 mg/100 g failed to increase alpha-tocopherol concentrations in extrahepatic tissues. Lung cytochrome P450 3A and 1A levels were unchanged by administration of alpha-tocopherol at any dose. In contrast, lung P-glycoprotein (MDR1) levels increased dose dependently and expression of this xenobiotic transport protein was correlated with lung alpha-tocopherol concentrations (R(2)=0.88, p<0.05). Increased lung MDR1 may provide protection from exposure to environmental toxins by increasing alveolar space alpha-tocopherol.

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    • "At the end of lactation, hepatic levels of α-T incorporation appear dramatically increased in offspring from both supplemented and nonsupplemented mothers, with differences between the two groups larger than at birth; in contrast, brain α-T concentrations show only a slight increment after lactation, with intergroup differences at P21 similar to those observed at P0. By revealing a high hepatic-tocerebral ratio of α-T incorporation in developing rats, such findings are in line with recent evidence in adult rats showing that infusions of pharmacological doses of α-T lead to much larger tocopherol accumulation in liver with respect to extrahepatic tissues [48]. α-T inhibitory effect on PKC activity has been documented in different cellular models in vitro, including neural cells [21–24,40], and confirmed in vivo in the hippocampus of α-T-supplemented adult rats [35]. "
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    • "Genetic factors are now identified to play a role in the physiological control of the intestinal absorption and transfer of vitamin E to chylomicrons and intestinal HDL [47] [48], and thus in the liver uptake and incorporation of vitamin E into nascent VLDL for peripheral tissues distribution [49]. Genetic factors are also at the basis of vitamin E catabolism and biliary elimination by the ABC transporters [50]. Tissue vitamin E delivery and uptake mechanisms in the extra-hepatic tissues remain poorly characterized and appear to be essentially associated to lipoprotein receptor expression and function (reviewed in [43]). "
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    • "Transport of vitamin E is highly dependent on lipid circulation changes in parallel with triglyceride levels (Thurnham et al 1986; Hacquebard & Carpentier 2005). Besides, the concentration of this vitamin in the liver is highly related to the concentration in plasma, the liver being the key organ for storage and regulation of circulating tocopherols (Mustacich et al 2007). In the present study, when diabetic animals were in the early stages of the disease (7 days), it was found that the levels of plasma lipids appeared with relatively low levels of tocopherol per lipid molecule. "
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