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7,8,3'-Trihydroxyflavone ameliorate oxidative stress in vivo and promotes neurite regeneration in vitro in rat retinal ganglion cells
- Source :
- European journal of pharmacology. 833
- Publication Year :
- 2018
-
Abstract
- In this study, we investigate the mechanism of 7,8,3'-Trihydroxyflavone (THF) on retinal oxidative stress and retinal ganglion cell (RGC) growth. Oxidative stress was induced by ocular hypertension (O.H.) in rat retina in vivo. Rats were then systemically injected with THF. We found THF ameliorated O.H.-induced oxidative stress in retina by reducing caspase-3 activity, downregulating MDA level and augmenting glutathione peroxidase expression. In addition, neonatal RGCs were cultured in vitro, and treated with THF. It was demonstrated that THF promoted neurite regeneration in RGC explant, and activated receptor kinase B (TrkB) signaling pathway through phosphorylation. In THF-treated RGC explant, application of TrkB antagonist, ANA12, effectively reversed the pro-neuronal effect of THF on promoting RGC neurite outgrowth, and inhibited TrkB signaling pathway through dephosphorylation. Thus, we concluded that THF could inhibit retinal oxidative stress and promote RGC growth through TrkB-dependent signaling pathway, thus providing a novel pharmaceutical candidate for glaucoma.
- Subjects :
- Male
Retinal Ganglion Cells
genetic structures
Neurite
Cell Survival
Neuronal Outgrowth
Primary Cell Culture
Tropomyosin receptor kinase B
medicine.disease_cause
Retinal ganglion
Retina
Rats, Sprague-Dawley
03 medical and health sciences
0302 clinical medicine
medicine
Neurites
Animals
Humans
Receptor, trkB
Regeneration
Phosphorylation
Pharmacology
Chemistry
Glaucoma
Flavones
eye diseases
Cell biology
Rats
Disease Models, Animal
Oxidative Stress
medicine.anatomical_structure
Retinal ganglion cell
030221 ophthalmology & optometry
Ocular Hypertension
sense organs
Signal transduction
030217 neurology & neurosurgery
Oxidative stress
Signal Transduction
Subjects
Details
- ISSN :
- 18790712
- Volume :
- 833
- Database :
- OpenAIRE
- Journal :
- European journal of pharmacology
- Accession number :
- edsair.doi.dedup.....3444b88c9e2cd01ee2321ae8568b78a3