| Alpha-lipoic acid prevents bupivacaine-induced neuron injury in vitro through a PI3K/Akt-dependent mechanism. | |
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MedLine Citation:
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PMID: 19879292 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Xiaohui Wang; Xiaojin Zhang; Yunlin Cheng; Chuanfu Li; Wenbo Zhang; Li Liu; Zhengnian Ding |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-10-29 |
Journal Detail:
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Title: Neurotoxicology Volume: 31 ISSN: 1872-9711 ISO Abbreviation: Neurotoxicology Publication Date: 2010 Jan |
Date Detail:
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Created Date: 2010-02-01 Completed Date: 2010-04-13 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7905589 Medline TA: Neurotoxicology Country: Netherlands |
Other Details:
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Languages: eng Pagination: 101-12 Citation Subset: IM |
Copyright Information:
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2009 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Anesthesiology, First Affiliated Hospital with Nanjing Medical University, Nanjing, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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1-Phosphatidylinositol 3-Kinase
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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:
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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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