1. ビタミンEについての栄養学的研究 : 特に生体内動態の解明について

抄録

Vitamin E is known as a fat-soluble antioxidative vitamin. It is naturally composed of eight analogs and of them, α -tocopherol (α -Toc) has the highest bioactivity. Synthetic a -Toc (all-rac-α-Toc) has therefore been used in medical drugs, food additives and cosmetics, because it is more inexpensive than the natural product. Synthetic α -Toc contains equal amounts of eight different stereoisomers arising from three ansynmetric carbons (2-position on chroman ring and 4'- and 8'- position in the side chain tail). First we determined the stereoisomers of a -Toc, especially 2R and 2S isomers, by chiral-HPLC. However, although we could not separate 2R isomers by chiral-HPLC, 2S isomers were separated into three peaks. The separate determination of 2S and 2R isomers then became practicable. Using HPLC, the dynamic analysis of a -Toc stereoisomers in vivo became possible. We investigated the distribution and biodiscrimination of a -Toc stereoisomers in rat tissues and human blood by this HPLC method. According to the obtained results, 2R- and 2S-isomers of a -Toc were easily transported into the liver from the small intestine through the lymphatic tube by no biodiscrimination after intestinal absorption in situ and in vitro. During transportation from the liver into the blood circulation, biodiscrinimation of a -Toc stereoisomers occured and 2R-isomers were preferentially released from the liver into blood plasma, whereas 2S-isomers remained in the liver. However, during prolonged feeding of all-rac- α -Toc 2S-isomers in the liver reduced to a low level and 2R-isomers became the predominant component of a -Toc. Consequently, we suggested that the α -Toc discrimination was performed by -tocopherol transfer protein (α -TTP) in the liver, whereas, the in vivo fate of the remained 2S-isomers of a -tocopherol was not elucidated at the start of this research. We therefore clarified the metabolic fate of both RRR- and SRR- α -tocopherol using [5-methyl-^14C]-RRR- and -SRR- α -tocopherol in rats. The obtained results showed that SRR- α -tocopherol was easily excreted into feces and urine, but the RRR-isomer remained in the body and was consumed as biological antioxidants. We also confirmed that the metabolite of RRR- α -tocopherol after normal antioxidant function was a-tocoquinone, but concentration of the latter in the blood and tissues was extremely low compared to the initial α-tocopherol. Finally, we identified the metabolite from the RSS-isomer of a -tocopherol as 2,5,7,8-tetramethyl-2-(2'-carboxyethyl)-6-hydroxy-chroman (α -CEHC) in urine. It is present in urine as a conjugate with glucuronide or sulfate. Similarly, the major metabolite of γ -tocopherol was 2,7,8-trimethyl-2-(2'-carboxyethyl)-6-hydroxy-Chroman (γ - CEHC). This γ -CEHC is known as a sodium excretion enhancing substance in rats. Also, we confirmed that the administration of γ -tocopherol or γ -tocotrienol increased the sodium excretion of sodium chloride loaded rats. This effect was increased with the simultaneous administration of α-tocopherol.