Antioxidant properties
of idebenone.
Mordente A, Martorana GE, Minotti G, Giardina B.
Institute of Biological Chemistry,
Catholic University School of Medicine,
Rome, Italy.
- Chem Res Toxicol 1998 Jan;11(1):54-63
Abstract
Idebenone is a synthetic
analogue of coenzyme Q that is currently employed in the treatment of vascular
and degenerative diseases of the central nervous system. There is some
evidence to suggest that idebenone might function as an antioxidant; however,
it has not been demonstrated whether this function pertains to the quinone or
hydroquinone form of idebenone. Here we demonstrate that idebenone can
scavenge a variety of free radical species, including organic radicals such as
2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and
diphenylpicrylhydrazyl, peroxyl and tyrosyl radicals, and peroxynitrite.
Idebenone can also redox couple with hypervalent species of Mb or Hb, thus
preventing lipid peroxidation promoted by these species. Likewise, idebenone
inhibits microsomal lipid peroxidation induced by ADP-iron complexes or
organic hydroperoxides. In so doing, idebenone prevents the destruction of
cytochrome P450, which otherwise would accompany lipid peroxidation.
Irrespective of the experimental system under investigation, idebenone
functions by virtue of the electron-donating properties of the hydroquinone
form. Redox coupling of this hydroquinone with free radicals generates the
quinone compound, which per se lacks antioxidant activity. In many
experiments, the antioxidant effects of idebenone become appreciable at
approximately 2 microM, which is well in the range of plasma levels attainable
in patients given oral doses of this drug. Moreover, comparative experiments
have shown that the antioxidant efficiency of idebenone varies from no less
than 50% to slightly more than 100% of that of vitamin E or Trolox. We would
therefore propose that the neuroprotective effects of idebenone can be
attributed, at least in part, to its ability to function as an antioxidant,
involving redox cycling between hydroquinone and quinone.
