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- Title
Bupivacaine Induces ROS-Dependent Autophagic Damage in DRG Neurons via TUG1/mTOR in a High-Glucose Environment.
- Authors
Lai, Luying; Wang, Yongwei; Peng, Shenghui; Guo, Wenjing; Wei, Guanshan; Li, Le; Xia, Zhengyuan; Li, Fengxian; Xu, Shiyuan
- Abstract
Bupivacaine (BP) is a commonly clinically used local anesthetic (LA). Current studies suggest that neurological complications are increased in diabetic patients after LA application, but the molecular mechanism is poorly understood. LA-induced autophagy and neuronal injury have been reported. We hypothesized that a high-glucose environment aggravates BP-induced autophagic damage. Mouse dorsal root ganglion (DRG) neurons were treated with BP in a high-glucose environment, and the results showed that reactive oxygen species (ROS) levels increased, autophagy was activated, autophagy flux was blocked, and cell viability decreased. Pretreatment with the ROS scavenger N-acetyl-cysteine (NAC) attenuated ROS-mediated autophagy regulation. Moreover, the expression of the long noncoding RNA (lncRNA) taurine upregulated gene 1 (TUG1) increased, and NAC and TUG1 siRNA inhibited the expression of TUG1/mammalian target of rapamycin (mTOR) in DRGs treated with BP in a high-glucose environment. Intriguingly, contrary to previous reports on a positive effect on neurons, we found that rapamycin, an autophagy activator, and chloroquine, an autophagy and lysosome inhibitor, both exacerbated autophagic damage. These data suggest that a high-glucose environment exacerbated BP induced ROS-dependent autophagic damage in DRG neurons through the TUG1/mTOR signaling pathway, which provides a theoretical basis and target for the clinical prevention and treatment of BP neurotoxicity in diabeties.
- Subjects
DORSAL root ganglia; LINCRNA; NEUROTOXICOLOGY; BUPIVACAINE; REACTIVE oxygen species; NEURONS
- Publication
Neurotoxicity Research, 2022, Vol 40, Issue 1, p111
- ISSN
1029-8428
- Publication type
Article
- DOI
10.1007/s12640-021-00461-8