Abstract
Local anesthetics are used routinely and effectively. However, many are also known to activate neurotoxic pathways. We tested the neuroprotective efficacy of ginkgolide B (GB), an active component of Ginkgo biloba, against ROS-mediated neurotoxicity caused by the local anesthetic bupivacaine. SH-SY5Y cells were treated with different concentrations of bupivacaine alone or following preincubation with GB. Pretreatment with GB increased SH-SY5Y cell viability and attenuated intracellular ROS accumulation, apoptosis, mitochondrial dysfunction, and ER stress. GB suppressed bupivacaine-induced mitochondrial depolarization and mitochondria complex I and III inhibition and increased cleaved caspase-3 and Htra2 expression, which was strongly indicative of activation of mitochondria-dependent apoptosis with concomitantly enhanced expressions of Grp78, caspase-12 mRNA, protein, and ER stress. GB also improved ultrastructural changes indicative of mitochondrial and ER damage induced by bupivacaine. These results implicate bupivacaine-induced ROS-dependent mitochondria, ER dysfunction, and apoptosis, which can be attenuated by GB through its antioxidant property.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects*
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Bupivacaine / toxicity*
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Caspase 12 / genetics
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Caspase 12 / metabolism
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Caspase 3 / metabolism
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Cell Shape / drug effects
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Cell Shape / genetics
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Cell Survival / drug effects
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Cell Survival / genetics
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Electron Transport Complex I / metabolism
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Electron Transport Complex III / metabolism
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Endoplasmic Reticulum Chaperone BiP
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Endoplasmic Reticulum Stress / drug effects
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Endoplasmic Reticulum Stress / genetics
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Enzyme Activation / drug effects
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Flow Cytometry
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Ginkgolides / pharmacology*
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Heat-Shock Proteins / genetics
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Heat-Shock Proteins / metabolism
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High-Temperature Requirement A Serine Peptidase 2
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Humans
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Lactones / pharmacology*
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Membrane Potential, Mitochondrial / drug effects
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Membrane Potential, Mitochondrial / genetics
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Mitochondria / drug effects
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Mitochondria / metabolism
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Mitochondria / ultrastructure
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Mitochondrial Proteins / metabolism
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Neuroprotective Agents / pharmacology*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Reactive Oxygen Species / metabolism
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Serine Endopeptidases / metabolism
Substances
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Endoplasmic Reticulum Chaperone BiP
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Ginkgolides
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HSPA5 protein, human
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Heat-Shock Proteins
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Lactones
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Mitochondrial Proteins
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Neuroprotective Agents
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RNA, Messenger
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Reactive Oxygen Species
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ginkgolide B
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Serine Endopeptidases
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HTRA2 protein, human
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High-Temperature Requirement A Serine Peptidase 2
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Caspase 12
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Caspase 3
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Electron Transport Complex I
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Electron Transport Complex III
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Bupivacaine