tocopheryl hemisuccinate may be the "best" form of vitamin E

Doug Skrecky (oberon@vcn.bc.ca)
Fri, 6 Nov 1998 22:40:21 -0800 (PST)

Citations: 1-2
<1>
Authors
Tirmenstein MA. Leraas TL. Fariss MW. Institution
Department of Pharmaceutical Sciences, College of Pharmacy and Graduate Program in Pharmacology/Toxicology, Washington State University, Pullman 99164-6510, USA.
Title
alpha-Tocopheryl hemisuccinate
administration increases rat liver subcellular alpha-tocopherol levels and protects against carbon tetrachloride-induced hepatotoxicity. Source
Toxicology Letters. 92(1):67-77, 1997 Jun 16. Abstract
Rats were administered a series of tocopherol analogs 18 h prior to a hepatotoxic dose of carbon tetrachloride (CCl4). Of the compounds tested, only d-alpha-tocopheryl hemisuccinate (TS) provided significant protection against CCl4-induced hepatotoxicity. No protection was observed with either d-alpha-tocopherol (alpha-T) or a tocopherol succinate ether derivative, d-alpha-tocopheryloxybutyric acid (TSE). None of the tocopherol analogs significantly inhibited CYP2E1 activity as measured by oxidation of p-nitrophenol. Liver homogenates and subcellular fractions
(cytosol, nuclei, plasma membranes, mitochondria and microsomes) were
collected 18 h after tocopherol analog administration in the absence of CCl4. Homogenate and subcellular alpha-T levels were not significantly increased following TSE administration but were increased 2-3 fold following TS and alpha-T administration. Total tocopherol levels (alpha-T+ TS + TSE) in liver homogenates and subcellular fractions were highest in rats supplemented with TS. In these animals, TS was detected in all subcellular fractions and total tocopherol levels were increased from 6-23 fold over those seen in controls and 2-9 fold over alpha-T treated rats. In vitro studies in which liver homogenates and subcellular fractions were peroxidized with ascorbate and ADP/Fe suggest that increasing levels of alpha-T but not TS correlates with increased protection against lipid peroxidation. These results suggest that the ability of TS to protect against CCl4-induced hepatotoxicity relates to its enhanced hepatic accumulation and subsequent hydrolysis to alpha-T.

<2>
Authors
Fariss MW. Fortuna MB. Everett CK. Smith JD. Trent DF. Djuric Z. Institution
Department of Pathology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0662.
Title
The selective antiproliferative effects of alpha-tocopheryl hemisuccinate and cholesteryl hemisuccinate on murine leukemia cells result from the action of the intact compounds. Source
Cancer Research. 54(13):3346-51, 1994 Jul 1. Abstract
In the present study we have established that the antitumor activity of alpha-tocopheryl succinate (TS, vitamin E succinate) and cholesteryl succinate (CS) result from the action of the intact TS and CS compounds and not from the release of alpha-tocopherol, cholesterol, or succinate. We report that treatment of murine leukemia cell lines C1498
(myeloid) and L1210 (lymphocytic), with the tris salts of TS or CS, but not
alpha-tocopherol and tris succinate or cholesterol and tris succinate, significantly inhibit the growth of these tumor cells and significantly enhance doxorubicin-induced tumor cell kill in a similar fashion. In contrast, the treatments mentioned above did not adversely affect the growth of murine normal bone marrow cells (colony-forming unit-granulocyte-macrophage). In fact, colony-forming unit granulocyte-macrophage cell growth was stimulated by exposure to CS and TS
(as well as their ether analogues) at concentrations above 100 microM.
Furthermore, pretreatment of colony-forming unit granulocyte-macrophage cells with TS or CS appears to protect these normal cells from the lethal effect of doxorubicin exposure. Selective inhibition of leukemia cell proliferation
(identical to that noted for CS and TS) was also observed following the
treatment of cells with the nonhydrolyzable ether forms of CS
(cholesteryloxybutyric acid) and TS
(alpha-tocopheryloxybutyric acid). These findings suggest
that TS, alpha-tocopheryloxybutyric acid, CS, and cholesteryloxybutyric acid may prove clinically useful as selective antitumor agents when administered alone or in combination with doxorubicin by a route that ensures tissue accumulation of the intact compound.