In vitro studies on the OH* and O2(-*) free radical scavenger properties of idebenone in chemical systems.
OH(*) free radicals were generated by Fenton reaction in the presence of bovine serum albumin (BSA). The decreasing water-solubility of BSA with increasing Fe(2+) concentrations of the system is a sensitive indicator of the cross-linking effects of the OH(*) free radicals. Idebenone (oxidized form) was solubilized for this experiment in DMSO and added to the system in final concentrations of 0.01 or 0.1%. Neither of these concentrations displayed any protective effect against the insolubilization of BSA. Therefore, oxidized idebenone has to be considered as a substance which reacts with OH(*) free radicals slower than the BSA itself, i.e., its oxidized form is not an efficient scavenger of this type of free radicals under the given circumstances. The ability of idebenone to scavenge superoxide radicals was tested in ( [Formula: see text] ) the pyrogallol system; and (ii) the xanthine-xanthine oxidase-nitro blue tetrazolium (XXO-NBT) system. Idebenone did not show any O(2)(-*) radical scavenging ability as revealed by these two in vitro methods, in the concentration ranges studied (up to 75 or 220 microg/ml, respectively). On the contrary, an increasing O(2)(-*) radical generation was observed with increasing concentrations of the drug in both test systems used. The possible biological significance of these observations is discussed in the light of other results like ESR spin trapping and measurements of superoxide dismutase (SOD) activity in various tissues.
Semsei
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NIH-NIA Gerontological Research Center, Baltimore, MD, USA.
Nagy
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Zs -Nagy
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