Protective effects of Fe-Aox29, a novel antioxidant derived from a molecular combination of Idebenone and vitamin E, in immortalized fibroblasts and fibroblasts from patients with Friedreich Ataxia.
Friedreich Ataxia (FRDA), the most frequent inherited ataxia, is not only characterized by progressive gait and limb ataxia, but in most cases is also accompanied by a severe hypertrophic cardiomyopathy. This life threatening symptom can be ameliorated by the administration of idebenone, a short chain quinone antioxidant, supporting additional evidence that oxidative stress plays a major role in the pathogenesis of this disease. In this study we analyze the combinatorial effect of different antioxidants on cell viability of FRDA fibroblasts and of RAT-1 immortalized fibroblasts exposed to oxidative stress. We find that an equimolar mixture of idebenone and vitamin E is more potent than each of the compound alone. Increased potency was also obtained with a novel synthetic antioxidant (Fe-Aox29) combining the active groups from both idebenone and vitamin E. These results indicate, that idebenone and vitamin E might act synergistically to counteract oxidative stress in fibroblasts from FRDA patients.
Jauslin
Matthias L
ML
Santhera Pharmaceuticals, Hammerstrasse 47, Liestal 4410, Switzerland.
Vertuani
Silvia
S
Durini
Elisa
E
Buzzoni
Lisa
L
Ciliberti
Nunzia
N
Verdecchia
Sara
S
Palozza
Paola
P
Meier
Thomas
T
Manfredini
Stefano
S
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D016227:Benzoquinones / Q000737:chemistry / Q000494:pharmacology*; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D002839:Chromans / Q000737:chemistry / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology; D005621:Friedreich Ataxia / Q000473:pathology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D020011:Protective Agents / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives; D014810:Vitamin E / Q000737:chemistry / Q000494:pharmacology*
D000975:Antioxidants; D016227:Benzoquinones; D002839:Chromans; C524291:Fe-Aox29; D020011:Protective Agents; D017382:Reactive Oxygen Species; D014451:Ubiquinone; D014810:Vitamin E; D006861:Hydrogen Peroxide; C036619:idebenone