Consequences of long-term oral administration of the mitochondria-targeted antioxidant MitoQ to wild-type mice.
The mitochondria-targeted quinone MitoQ protects mitochondria in animal studies of pathologies in vivo and is being developed as a therapy for humans. However, it is unclear whether the protective action of MitoQ is entirely due to its antioxidant properties, because long-term MitoQ administration may alter whole-body metabolism and gene expression. To address this point, we administered high levels of MitoQ orally to wild-type C57BL/6 mice for up to 28 weeks and investigated the effects on whole-body physiology, metabolism, and gene expression, finding no measurable deleterious effects. In addition, because antioxidants can act as pro-oxidants under certain conditions in vitro, we examined the effects of MitoQ administration on markers of oxidative damage. There were no changes in the expression of mitochondrial or antioxidant genes as assessed by DNA microarray analysis. There were also no increases in oxidative damage to mitochondrial protein, DNA, or cardiolipin, and the activities of mitochondrial enzymes were unchanged. Therefore, MitoQ does not act as a pro-oxidant in vivo. These findings indicate that mitochondria-targeted antioxidants can be safely administered long-term to wild-type mice.
Department of Clinical Biochemistry, University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Cambridge CB2 0QQ, UK.
Sergio
S
Rodriguez-Cuenca
Helena M
HM
Cochemé
Angela
A
Logan
Irina
I
Abakumova
Tracy A
TA
Prime
Claudia
C
Rose
Antonio
A
Vidal-Puig
Anthony C
AC
Smith
David C
DC
Rubinsztein
Ian M
IM
Fearnley
Bruce A
BA
Jones
Simon
S
Pope
Simon J R
SJ
Heales
Brian Y H
BY
Lam
Sudeshna Guha
SG
Neogi
Ian
I
McFarlane
Andrew M
AM
James
Robin A J
RA
Smith
Michael P
MP
Murphy
D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D009943:Organophosphorus Compounds / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology*; D018384:Oxidative Stress; D014451:Ubiquinone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D000975:Antioxidants; D009943:Organophosphorus Compounds; D014451:Ubiquinone; C429014:mitoquinone