Document Detail


Alpha-lipoic acid prevents bupivacaine-induced neuron injury in vitro through a PI3K/Akt-dependent mechanism.
MedLine Citation:
PMID:  19879292     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Bupivacaine is an amide type local anesthetic which is widely used for epidural anesthesia and nerve blockade in patients. However, local administration of bupivacaine could cause neuron injury showing transient neurologic symptoms. alpha-Lipoic acid (LA) was shown to protect nerve cells from substance-induced injury. We hypothesized that LA administration could attenuate bupivacaine-induced neurotoxicity. METHODS: To evaluate our hypothesis, we treated mouse neuroblastoma N2a cells with LA 30 min before the cells were exposed to bupivacaine. We evaluated cellular injury by examination of cell viability, morphology changes, nuclear condensation, and Annexin V staining. We also examined the levels of intracellular reactive oxygen species (ROS) and activation of PI3K/Akt signaling pathway. In a separate experiment, we determined the effect of Akt inhibition on cell viability in the presence of LA and bupivacaine. RESULTS: Bupivacaine treatment significantly induced cell injury as evidenced by decreased cell viability, increased nuclear condensation and Annexin V staining. Administration of LA significantly attenuated bupivacaine-induced cell injury. In addition, LA treatment increased the levels of phospho-Akt and phospho-GSK3beta and attenuated bupivacaine decreased the levels of ROS. More significantly, pharmacological inhibition of Akt abolished the LA-induced protection from bupivacaine-caused cell injury. CONCLUSIONS: Our findings suggest that pretreatment of neuroblastoma cells with LA protected neural cells from bupivacaine-induced injury. The mechanisms involve activation of the PI3K/Akt signaling pathway.
Authors:
Xiaohui Wang; Xiaojin Zhang; Yunlin Cheng; Chuanfu Li; Wenbo Zhang; Li Liu; Zhengnian Ding
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-10-29
Journal Detail:
Title:  Neurotoxicology     Volume:  31     ISSN:  1872-9711     ISO Abbreviation:  Neurotoxicology     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-02-01     Completed Date:  2010-04-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7905589     Medline TA:  Neurotoxicology     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  101-12     Citation Subset:  IM    
Copyright Information:
2009 Elsevier Inc. All rights reserved.
Affiliation:
Department of Anesthesiology, First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
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MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase / metabolism*
Anesthetics, Local / pharmacology*
Animals
Animals, Newborn
Annexin A5 / metabolism
Apoptosis / drug effects
Bupivacaine / pharmacology*
Cell Line, Tumor
Cells, Cultured
Dose-Response Relationship, Drug
Drug Interactions
Enzyme Inhibitors / pharmacology
Hippocampus / cytology
L-Lactate Dehydrogenase / metabolism
Mice
Mice, Inbred C57BL
Neuroblastoma / pathology
Neurons / drug effects*
Phosphorylation / drug effects
Proto-Oncogene Proteins c-akt / metabolism*
Reactive Oxygen Species / metabolism
Tetrazolium Salts / diagnostic use
Thiazoles / diagnostic use
Thioctic Acid / pharmacology*
Time Factors
Vitamin B Complex / pharmacology*
Chemical
Reg. No./Substance:
0/Anesthetics, Local; 0/Annexin A5; 0/Enzyme Inhibitors; 0/Reactive Oxygen Species; 0/Tetrazolium Salts; 0/Thiazoles; 12001-76-2/Vitamin B Complex; 2180-92-9/Bupivacaine; 298-93-1/thiazolyl blue; 62-46-4/Thioctic Acid; EC 1.1.1.27/L-Lactate Dehydrogenase; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.11.1/Proto-Oncogene Proteins c-akt

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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