Oxidative stress plays a pivotal role in the pathogenesis of several
chronic diseases and
antioxidants may represent potential tools for the prevention of these diseases. Here, we investigated the
antioxidant efficiency of different
tocotrienol isoforms (alpha-, delta-, gamma-
tocotrienols), and that of
FeAox-6, a novel synthetic compound which combines, by a stable covalent bond, the chroman head of
vitamin E and a polyisoprenyl sequence of four conjugated double bonds into a single molecule. The
antioxidant efficiency was evaluated as the ability of the compounds to inhibit lipid peroxidation,
reactive oxygen species (ROS) production, heat
shock protein (hsp) expression in rat liver microsomal membranes as well as in RAT-1 immortalized fibroblasts challenged with different
free radical sources, including
2,2'-azobis(2-amidinopropane) (
AAPH),
tert-butyl hydroperoxide (tert-BOOH) and H2O2. Our results show that individual
tocotrienols display different
antioxidant potencies. Irrespective of the prooxidant used, the order of effectiveness was:
delta-tocotrienol >
gamma-tocotrienol =
alpha-tocotrienol in both isolated membranes and intact cells. This is presumably due to the decreased methylation of
delta-tocotrienol chromane ring, which allows the molecule to be more easily incorporated into cell membranes. Moreover, we found that
FeAox-6 showed an
antioxidant potency greater than that of
delta-tocotrienol. Such an efficiency seems to depend on the concomitant presence of a chromane ring and a phytyl chain in the molecule, which because of four conjugated double bonds, may induce a greater mobility and a more uniform distribution within cell membrane. In view of these results,
FeAox-6 represents a new potential preventive agent in
chronic diseases in which oxidative stress plays a pathogenic role.