A synthetic cell permeable antioxidant protects neurons against acute oxidative stress.
Nicola J DrummondNick O DaviesJanet E LovettMark R MillerGraeme CookThomas BeckerCatherina G BeckerDonald B McPhailTilo KunathPublished in: Scientific reports (2017)
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.
Keyphrases
- oxidative stress
- induced apoptosis
- cell free
- single cell
- reactive oxygen species
- dna damage
- cell therapy
- liver failure
- ischemia reperfusion injury
- diabetic rats
- respiratory failure
- endoplasmic reticulum stress
- drug induced
- anti inflammatory
- atrial fibrillation
- adipose tissue
- spinal cord
- high intensity
- signaling pathway
- single molecule
- cell proliferation
- body mass index
- physical activity
- metabolic syndrome
- aortic dissection
- bone marrow
- subarachnoid hemorrhage
- extracorporeal membrane oxygenation
- hepatitis b virus