title: 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.
abstract: 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.
authors.affiliation: Santhera Pharmaceuticals, Hammerstrasse 47, Liestal 4410, Switzerland.
authors.forename: Matthias L
authors.initials: ML
authors.lastname: Jauslin
authors.forename: Silvia
authors.initials: S
authors.lastname: Vertuani
authors.forename: Elisa
authors.initials: E
authors.lastname: Durini
authors.forename: Lisa
authors.initials: L
authors.lastname: Buzzoni
authors.forename: Nunzia
authors.initials: N
authors.lastname: Ciliberti
authors.forename: Sara
authors.initials: S
authors.lastname: Verdecchia
authors.forename: Paola
authors.initials: P
authors.lastname: Palozza
authors.forename: Thomas
authors.initials: T
authors.lastname: Meier
authors.forename: Stefano
authors.initials: S
authors.lastname: Manfredini
mesh_terms: 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*
chemical_list: 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