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Monosialoganglioside protects against bupivacaine-induced neurotoxicity caused by endoplasmic reticulum stress in rats

Authors Liu B, Ji J, Feng Q, Luo X, Yan X, Ni Y, He Y, Mao Z, Liu J

Received 25 October 2018

Accepted for publication 10 January 2019

Published 19 February 2019 Volume 2019:13 Pages 707—718

DOI https://doi.org/10.2147/DDDT.S192225

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Andrew Yee

Peer reviewer comments 2

Editor who approved publication: Dr Qiongyu Guo


Benquan Liu,1 Jiemei Ji,1 Qing Feng,1 Xi Luo,1 Xiurong Yan,1 Yuxia Ni,2 Yajun He,1 Zhongxuan Mao,1 Jingchen Liu1

1Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, People’s Republic of China; 2Department of Anesthesiology, Langdong Hospital of Guangxi Medical University, Nanning 530021, Guangxi, People’s Republic of China

Background: Local anesthetics in spinal anesthesia have neurotoxic effects, resulting in severe neurological complications. Intrathecal monosialoganglioside (GM1) administration has a therapeutic effect on bupivacaine-induced neurotoxicity. The aim of this study was to determine the underlying mechanisms of bupivacaine-induced neurotoxicity and the potential neuroprotective role of GM1.
Materials and methods: A rat spinal cord neurotoxicity model was established by injecting bupivacaine (5%, 0.12 µL/g) intrathecally. The protective effect of GM1 (30 mg/kg) was evaluated by pretreating the animals with it prior to the bupivacaine regimen. The neurological and locomotor functions were assessed using standard tests. The histomorphological changes, neuron degeneration and apoptosis, and endoplasmic reticulum stress (ERS) relevant markers were analyzed using immunofluorescence, quantitative real-time PCR, and Western blotting.
Results: Bupivacaine resulted in significant neurotoxicity in the form of aberrant neurolocomoter functions and spinal cord histomorphology and neuronal apoptosis. Furthermore, the ERS specific markers were significantly upregulated during bupivacaine-induced neurotoxicity. These neurotoxic effects were ameliorated by GM1.
Conclusion: Pretreatment with GM1 protects against bupivacaine-induced neurotoxicity via the inhibition of the GRP78/PERK/eIF2α/ATF4-mediated ERS.

Keywords: bupivacaine, GM1 ganglioside, ERS, neurotoxicity
 

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