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Authors Wang S, Xia B, Qiao Z, Duan L, Wang G, Meng W, Liu Z, Wang Y, Zhang M
Received 27 November 2018
Accepted for publication 26 February 2019
Published 17 April 2019 Volume 2019:13 Pages 1187—1196
DOI https://doi.org/10.2147/DDDT.S196172
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Colin Mak
Peer reviewer comments 4
Editor who approved publication: Dr Tuo Deng
Background: Bupivacaine
(BUP) acts as a local anesthetic, which is extensively used for clinical
patients but could generate neurotoxicity in neurons. Tetramethylpyrazine (TET)
exhibits strong neuron protective effects against neurotoxicity. Hence, we
investigate the effect of TET on BUP-induced neurotoxicity in SH-SY5Y cells.
Methods: CCK-8
assay was used to detect cell proliferation in SH-SY5Y cells. In addition,
Western blotting was used to examine Bax, Bcl-2, active caspase 3, LC3II,
Beclin 1 and p-62 protein levels in cells. Moreover, ELISA assay was used to
detect the levels of total glutathione (GS), superoxide dismutase (SOD) and
malondialdehyde (MDA) in cells.
Results: In this
study, we found that TET attenuated the neurotoxicity of BUP on SH-SY5Y cells.
Meanwhile, TET alleviated BUP-induced apoptosis in SH-SY5Y cell via decreasing
the expressions of active caspase-3 and Bax and increasing the expression of
Bcl-2. In addition, monodansylcadaverine staining assay and Western blotting
results confirmed that TET induced autophagy in SH-SY5Y cells via increasing
the LC3II/I and Beclin 1 levels. Furthermore, TET attenuated BUP-induced
oxidative damage in SH-SY5Y cells via upregulation of the levels of total GS
and SOD and downregulation of the level of MDA. Interesting, the protective
effects of TET against BUP-induced neurotoxicity in SH-SY5Y cells were reversed
by autophagy inhibitor 3-methyladenine (3MA).
Conclusion: These
data indicated that TET may play a neuroprotective role via inhibiting apoptosis
and inducing autophagy in SH-SY5Y cells. Therefore, TET may be a potential
agent for the treatment of human neurotoxicity induced by BUP.
Keywords: tetramethylpyrazine,
bupivacaine, neurotoxicity, human neuroblastoma cell