ANTIOXIDANT PROPERTIES OF HOXY-5-METHYL-6-(10-HYDROXYDECYL)-1,4-BENZOQUINONE (IDEBENONE)

Idebenone oxy-5-methyl-6-(10-hydroxydecyl)-1,4-benzoquinone] is a synt hetic analogue of coenzyme Q that is currently employed in the treatme nt of vascular and degenerative diseases of the central nervous system . There is some evidence to suggest that idebenone might function as a n antioxidant; however, it has not been demonstrated whether this func tion pertains to the quinone or hydroquinone form of idebenone. Here w e demonstrate that idebenone can scavenge a variety of free radical sp ecies, including organic radicals such as 2,2'-azinobis(3-ethylbenzoth iazoline-6-sulfonic acid) and diphenylpicrylhydrazyl, peroxyl and tyro syl radicals, and peroxynitrite. Idebenone can also redox couple with hypervalent species of Mb or Hb, thus preventing lipid peroxidation pr omoted 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, w hich otherwise would accompany lipid peroxidation. Irrespective of the experimental system under investigation, idebenone functions by virtu e 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 experiment s, the antioxidant; effects of idebenone become appreciable at similar to 2 mu M, which is well in the range of plasma levels attainable in patients given oral doses of this drug. Moreover, comparative experime nts have shown that the antioxidant efficiency of idebenone varies fro m 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 func tion as an antioxidant, involving redox cycling between hydroquinone a nd quinone.