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02 July 2016 : Laboratory Research  

7, 8, 3’-Trihydroxyflavone Promotes Neurite Outgrowth and Protects Against Bupivacaine-Induced Neurotoxicity in Mouse Dorsal Root Ganglion Neurons

Haohong ShiABCDEF, Xingjing LuoACD

DOI: 10.12659/MSM.896961

Med Sci Monit 2016; 22:2301-2308

Abstract

BACKGROUND: 7, 8, 3’-trihydroxyflavone (THF) is a novel pro-neuronal small molecule that acts as a TrkB agonist. In this study, we examined the effect of THF on promoting neuronal growth and protecting anesthetics-induced neurotoxicity in dorsal root ganglion (DRG) neurons in vitro.

MATERIAL AND METHODS: Neonatal mouse DRG neurons were cultured in vitro and treated with various concentrations of THF. The effect of THF on neuronal growth was investigated by neurite outgrowth assay and Western blot. In addition, the protective effects of THF on bupivacaine-induced neurotoxicity were investigated by apoptosis TUNEL assay, neurite outgrowth assay, and Western blot, respectively.

RESULTS: THF promoted neurite outgrowth of DRG neurons in dose-dependent manner, with an EC50 concentration of 67.4 nM. Western blot analysis showed THF activated TrkB signaling pathway by inducing TrkB phosphorylation. THF also rescued bupivacaine-induced neurotoxicity by reducing apoptosis and protecting neurite retraction in DRG neurons. Furthermore, the protection of THF in bupivacaine-injured neurotoxicity was directly associated with TrkB phosphorylation in a concentration-dependent manner in DRG neurons.

CONCLUSIONS: THF has pro-neuronal effect on DRG neurons by promoting neurite growth and protecting against bupivacaine-induced neurotoxicity, likely through TrkB activation.

Keywords: Bupivacaine - toxicity, Dose-Response Relationship, Drug, Flavones - pharmacology, Ganglia, Spinal - pathology, Neurites - pathology, Neuronal Outgrowth - drug effects, Neurons - pathology, Protective Agents - pharmacology, Receptor, trkB - metabolism, Signal Transduction - drug effects

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750