Antioxidant properties of MitoTEMPOL and its hydroxylamine.
Piperidine nitroxides such as TEMPOL have been widely used as antioxidants in vitro and in vivo. MitoTEMPOL is a mitochondria-targeted derivative of TEMPOL designed to protect mitochondria from the oxidative damage that they accumulate, but once there is rapidly reduced to its hydroxylamine, MitoTEMPOL-H. As little is known about the antioxidant efficacy of hydroxylamines, this study has assessed the antioxidant activity of both MitoTEMPOL and MitoTEMPOL-H. The hydroxylamine was more effective at preventing lipid-peroxidation than MitoTEMPOL and decreased oxidative damage to mitochondrial DNA caused by menadione. In contrast to MitoTEMPOL, MitoTEMPOL-H has no superoxide dismutase activity and its antioxidant actions are likely to be mediated by hydrogen atom donation. Therefore, even though MitoTEMPOL is rapidly reduced to MitoTEMPOL-H in cells, it remains an effective antioxidant. Furthermore, as TEMPOL is also reduced to a hydroxylamine in vivo, many of its antioxidant effects may also be mediated by its hydroxylamine.
Trnka
Jan
J
MRC Dunn Human Nutrition Unit, Cambridge, UK.
Blaikie
Frances H
FH
Logan
Angela
A
Smith
Robin A J
RA
Murphy
Michael P
MP
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D004272:DNA, Mitochondrial / Q000187:drug effects; D019811:Hydroxylamine / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects*; D010084:Oxidation-Reduction / Q000187:drug effects; D016133:Polymerase Chain Reaction; D051381:Rats; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D003497:Cyclic N-Oxides; D004272:DNA, Mitochondrial; D013113:Spin Labels; D019811:Hydroxylamine; D013482:Superoxide Dismutase; C001803:tempol; C505333:TEMPOL-H