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Biomed Pharmacother. 2018 Jul;103:1545-1551. doi: 10.1016/j.biopha.2018.04.155. Epub 2018 May 7.

Resveratrol protects bupivacaine-induced neuro-apoptosis in dorsal root ganglion neurons via activation on tropomyosin receptor kinase A.

Author information

1
Department of Orthopedic, No. 89 Hospital of Chinese PLA, Weifang, 261021, China.
2
Medicine Research Center, Weifang Medical University, Weifang, Shandong, 261053, China.
3
Medicine Research Center, Weifang Medical University, Weifang, Shandong, 261053, China. Electronic address: mincheng_Frank@aol.com.

Abstract

BACKGROUND:

General anesthesia in spinal cord may lead to unexpected but irreversible neurotoxicity. We investigated whether resveratrol (RSV) may protect bupivacaine (BUP)-induced neuro-apoptosis in spinal cord dorsal root ganglia (DRG).

METHODS:

Mouse DRG cells were cultured in vitro, pre-treated with RSV and then 5 mM BUP. A concentration-dependent effect of RSV on reducing BUP-induced apoptosis of DRG neurons (DRGNs) was evaluated using a TUNEL assay. QRT-PCR and western blot assays were also conducted to evaluate gene and protein expressions of tropomyosin receptor kinase A/B/C (TrkA/B/C) and activated (phosphorylated) Trk receptors, phospho-TrkA/B/C. In addition, a functional TrkA blocking antibody MNAC13 was applied in DRG culture to further measure the functional role of Trk receptor in RSV-initiated apoptotic protection on BUP-damaged DRGNs.

RESULTS:

BUP promoted significant apoptosis in DRG. RSV exhibited protective effects against BUP-induced neuro-apoptosis in a concentration-dependent manner. qRT-PCR and western blot showed that RSV did not alter TrkA/B/C gene or protein expression, but significantly upregulated phospho-TrkA. Conversely, application of MNAC13 decreased phospho-TrkA and reversed RSV-initiated neuro-protection on BUP-induced DRGN apoptosis.

CONCLUSION:

Resveratrol may protect anesthesia-induced DRG neuro-apoptosis, and activation of TrkA signaling pathway may be the underlying mechanism in this process.

KEYWORDS:

Anesthesia; Bupivacaine; Dorsal root ganglion neuron; Resveratrol; Spinal cord; TrkA

PMID:
29864941
DOI:
10.1016/j.biopha.2018.04.155
[Indexed for MEDLINE]

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