title: The effects of hispidulin on bupivacaine-induced neurotoxicity: role of AMPK signaling pathway.
abstract: Bupivacaine is a sodium channel blocker, which is widely used for local infiltration nerve block, epidural and intrathecal anesthesia. However, bupivacaine could cause nerve damage. Hispidulin was shown to be able to penetrate the blood-brain barrier and possess antiepileptic activity. In this study, we investigate whether hispidulin administration could attenuate bupivacaine-induced neurotoxicity. Bupivacaine-challenged mouse neuroblastoma N2a cells were treated with hispidulin. The neuron injury was assessed by examination of cell viability and apoptosis. The levels of activation of AMP-activated protein kinase (AMPK) signaling pathway were examined along with the effect of blocking AMPK signaling on cell viability in the presence of hispidulin and bupivacaine. Our results showed that Bupivacaine treatment significantly decreased cell viability and induced apoptosis. Treatment with hispidulin significantly attenuated bupivacaine-induced cell injury. In addition, hispidulin treatment increased the levels of phospho-AMPK and phospho-GSK3β and attenuated bupivacaine-induced loss in mitochondrial membrane potential. Furthermore, we found that blocking AMPK signaling pathway significantly abolished the cytoprotective effect of hispidulin against bupivacaine-induced cell injury. Our findings suggest that treatment of neuroblastoma cells with hispidulin-protected neural cells from Bupivacaine-induced injury via the activation of the AMPK/GSK3β signaling pathway.
authors.forename: Xinhuan
authors.initials: X
authors.lastname: Niu
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Zhou
authors.forename: Song
authors.initials: S
authors.lastname: Li
authors.forename: Mengyuan
authors.initials: M
authors.lastname: Zhang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002045:Bupivacaine / Q000633:toxicity*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D047309:Flavones / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000633:toxicity*; D010766:Phosphorylation / Q000187:drug effects; D059748:Proteolysis / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D047309:Flavones; D018696:Neuroprotective Agents; D009498:Neurotoxins; D055372:AMP-Activated Protein Kinases; D053148:Caspase 3; C055957:hispidulin; D002045:Bupivacaine