Amitriptyline Protects Against Lidocaine-induced Neurotoxicity in SH-SY5Y Cells via Inhibition of BDNF-mediated Autophagy.

Abstract

Amitriptyline (AMI) is a traditional tricyclic antidepressant that has been proven to exhibit neuroprotective effects in various neurological disorders. However, the underlying mechanism by which AMI attenuates lidocaine-induced neurotoxicity remains poorly understood. Brain-derived neurotrophic factor (BDNF) is an essential neurotrophin to neuronal development and survival in the brain, and recent studies have suggested that BDNF plays an important role in mediating lidocaine-induced neurotoxicity. The present study was performed to evaluate the protective effect of AMI against the neurotoxicity induced by lidocaine and to explore the role of BDNF-dependent autophagy in this process. The data showed that AMI pretreatment alleviated lidocaine-induced neurotoxicity, as evidenced by the restoration of cell viability, normalization of cell morphology, and reduction in the cell apoptosis index. In addition, autophagy inhibitor 3-methyladenine (3-MA) had a protective effect similar to that of AMI, but autophagy activator rapamycin eliminated the protective effect of AMI by suppressing mTOR activation. Moreover, at the molecular level, we found that AMI-mediated autophagy was involved in the expression of BDNF. The overexpression of BDNF or application of exogenous recombinant BDNF significantly suppressed autophagy and protected SH-SY5Y cells from apoptosis induced by Lido, whereas the neuroprotection of AMI was abolished by either knockdown of BDNF or use of a tropomyosin-related kinase B (TrkB) inhibitor ANA-12 in SH-SY5Y cells. Overall, our findings demonstrated that the protective effect of AMI against lidocaine-induced neurotoxicity correlated with inhibition of autophagy activity through upregulation of BDNF expression.

• Authors: Honghong Zhang, Xiaohui Chen, Ting Zheng, Mingxue Lin, Pinzhong Chen, Yanling Liao, Cansheng Gong, Fei Gao, Xiaochun Zheng
• Journal: Neurotoxicity research (Neurotox Res) Vol. 39 Issue 2 Pg. 133-145 (Apr 2021) ISSN: 1476-3524 [Electronic] United States
• PMID: 33156513 (Publication Type: Journal Article)

Chemical References

• Brain-Derived Neurotrophic Factor
• Neuroprotective Agents
• Amitriptyline
• BDNF protein, human
• Lidocaine

Topics

• Amitriptyline (administration & dosage)
• Apoptosis (drug effects)
• Autophagy (drug effects)
• Brain-Derived Neurotrophic Factor (antagonists & inhibitors)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Humans
• Lidocaine (toxicity)
• Neuroprotective Agents (administration & dosage)