The Ganglioside GM‐1 Inhibits Bupivacaine‐Induced Neurotoxicity in Mouse Neuroblastoma Neuro2a Cells. (August 2016)

• Record Type: Journal Article
• Authors: Liang, Yujie; Ji, Jiemei; Lin, Yunan; He, Yajun; Liu, Jingchen
• Is Part Of: Cell biochemistry and function. Volume 34:Number 6(2016)
• Page Start: 455
• Page End: 462
• Publication Date: 2016-08
• Subjects: apoptosis -- bupivacaine -- gangliosides -- neurotoxicity -- N2a cell; Cytochemistry -- Periodicals; Cell metabolism -- Periodicals; Biochemistry -- Periodicals; Cytology -- Periodicals; 572
• DOI: 10.1002/cbf.3208
• Languages: English
• ISSNs: 0263-6484

Abstract

Abstract : Objective: Studies indicate that bupivacaine‐induced neurotoxicity results from apoptosis. Gangliosides have been shown to promote neuronal repair and recovery of neurological function after spinal cord injury. Previously, we confirmed that in vivo administration of the ganglioside GM‐1 attenuated bupivacaine‐induced neurotoxicity in various animal models; however, the underlying mechanism remains unclear. Methods: Cells of the neuroblastoma line N2a (Neuro2a cells) were divided into three experimental groups: control, bupivacaine‐treated, and bupivacaine‐treated with GM‐1 pretreatment. Cell viability and apoptosis were assessed through CCK‐8 assays, Hoechst staining, and flow cytometry analysis of Annexin‐V/propidium iodide double labeling. Real‐time polymerase chain reaction and western blotting assessed the expression of caspase‐3, caspase‐8, and caspase‐9. Results: Bupivacaine‐induced apoptosis worsened with increasing dose and exposure time. Bupivacaine induced increased expression of caspase‐3 and caspase‐9, but not caspase‐8, indicating that the mitochondrial pathway but not the death receptor apoptosis pathway was activated. GM‐1 pretreatment inhibited bupivacaine‐induced apoptosis and the expression of caspase‐3 and caspase‐9 in a dose‐dependent manner. Conclusion: Bupivacaine induced neurotoxicity by activating apoptosis via the mitochondrial pathway, and this was inhibited by GM‐1 pretreatment.