We previously reported that tocotrienols acted as more potent inhibitors against selenium deficiency–induced cell death than the corresponding tocopherol isoforms (J. Biol. Chem. 2003;278:39428–39434). In the present study, we first compared the differences in the cellular uptake between α- tocopherol (α-Toc) and _-tocotrienol (α-Toc-3). The initial rate of cellular uptake of α-Toc-3 was 70-fold higher than that of α-Toc. Subcellular fractionation analysis of _-Toc-3 and α-Toc–fortified cells showed similar cellular distribution of these antioxidants, which was directly proportional to the lipid distribution. The cells containing similar amounts of α-Toc-3 and α-Toc showed similar resistance against the oxidative stress caused by peroxides.
These results suggest that the apparent higher cytoprotective effect of α-Toc-3 than α-Toc is primarily ascribed to its higher cellular uptake.