A synthetic cell permeable antioxidant protects neurons against acute oxidative stress

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...

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Autores principales:	Nicola J. Drummond, Nick O. Davies, Janet E. Lovett, Mark R. Miller, Graeme Cook, Thomas Becker, Catherina G. Becker, Donald B. McPhail, Tilo Kunath
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5b82113a13a54e099d73eb170227c970
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spelling	oai:doaj.org-article:5b82113a13a54e099d73eb170227c9702021-12-02T15:05:29ZA synthetic cell permeable antioxidant protects neurons against acute oxidative stress10.1038/s41598-017-12072-52045-2322https://doaj.org/article/5b82113a13a54e099d73eb170227c9702017-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-12072-5https://doaj.org/toc/2045-2322Abstract 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.Nicola J. DrummondNick O. DaviesJanet E. LovettMark R. MillerGraeme CookThomas BeckerCatherina G. BeckerDonald B. McPhailTilo KunathNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nicola J. Drummond Nick O. Davies Janet E. Lovett Mark R. Miller Graeme Cook Thomas Becker Catherina G. Becker Donald B. McPhail Tilo Kunath A synthetic cell permeable antioxidant protects neurons against acute oxidative stress
description	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.
format	article
author	Nicola J. Drummond Nick O. Davies Janet E. Lovett Mark R. Miller Graeme Cook Thomas Becker Catherina G. Becker Donald B. McPhail Tilo Kunath
author_facet	Nicola J. Drummond Nick O. Davies Janet E. Lovett Mark R. Miller Graeme Cook Thomas Becker Catherina G. Becker Donald B. McPhail Tilo Kunath
author_sort	Nicola J. Drummond
title	A synthetic cell permeable antioxidant protects neurons against acute oxidative stress
title_short	A synthetic cell permeable antioxidant protects neurons against acute oxidative stress
title_full	A synthetic cell permeable antioxidant protects neurons against acute oxidative stress
title_fullStr	A synthetic cell permeable antioxidant protects neurons against acute oxidative stress
title_full_unstemmed	A synthetic cell permeable antioxidant protects neurons against acute oxidative stress
title_sort	synthetic cell permeable antioxidant protects neurons against acute oxidative stress
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/5b82113a13a54e099d73eb170227c970
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A synthetic cell permeable antioxidant protects neurons against acute oxidative stress

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