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A synthetic cell permeable antioxidant protects neurons against acute oxidative stress

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Author(s)

Nicola Drummond, Nick Davies, Janet Eleanor Lovett, Mark Miller, Graeme Cook, Thomas Becker, Catherina Becker, Donald McPhail, Tilo Kunath

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Abstract

Excessive reactive oxygen species (ROS) can damage proteins, lipids, and DNA, which result in cell damage and death. The outcomes can be acute, as seen in stroke, or more chronic as observed in age-related diseases such as Parkinson’s disease. Here we investigate the antioxidant ability of a novel synthetic flavonoid, Proxison (7-decyl-3-hydroxy-2-(3,4,5-trihydroxyphenyl)-4-chromenone), using a range of in vitro and in vivo approaches. We show that, while it has radical scavenging ability on par with other flavonoids in a cell-free system, Proxison is orders of magnitude more potent than natural flavonoids at protecting neural cells against oxidative stress and is capable of rescuing damaged cells. The unique combination of a lipophilic hydrocarbon tail with a modified polyphenolic head group promotes efficient cellular uptake and moderate mitochondrial enrichment of Proxison. Importantly, in vivo administration of Proxison demonstrated effective and well tolerated neuroprotection against cell loss in a zebrafish model of dopaminergic neurodegeneration.
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Original languageEnglish
Article number11857
Number of pages12
JournalScientific Reports
Volume7
DOIs
StatePublished - 19 Sep 2017

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