title: Effect of parthanatos on ropivacaine-induced damage in SH-SY5Y cells.
abstract: Ropivacaine is one of the most common but toxic local anaesthetics, and the mechanisms underlying its neurotoxicity are still largely unknown. This study was conducted to prepare a ropivacaine-induced neuronal injury model and research the effects of ropivacaine on PARP-1 activation and nicotinamide adenine dinucleotide (NAD)+depletion. The cell death and apoptosis of ropivacaine-induced SH-SY5Y cells were detected with flow cytometry. The lactate dehydrogenase cycling reaction measured the NAD+level, and western blots were used to analyze the expression levels of PARP-1 and apoptosis-inducing factor (AIF) after ropivacaine treatments with different concentrations and durations. A PARP-1 inhibitor (PJ-34) was used to confirm the relationship between PARP-1 activation and NAD+depletion. Hoechst 33258 nuclear staining and a mitochondrial membrane potential (Δψm) assay were used to detect the role of exogenous NAD+in ropivacaine-induced neuronal injury. Ropivacaine-induced SH-SY5Y cell death and apoptosis, PARP-1 activation, and AIF increase as well as intracellular NAD+depletion occurred in a time- and concentration-dependent manner (P<.05). PARP-1 activation led to NAD+depletion (P<.05). Exogenous NAD+impaired ropivacaine-induced nuclear injury (P<.05). Ropivacaine treatment induced PARP-1 activation and NAD+depletion (P<.05). Parthanatos (PARP-1-dependent cell death) was definitely involved in ropivacaine-induced neuronal injury, and exogenous NAD+may be a novel therapeutic method for parthanatos-dependent neuronal injury.
authors.affiliation: Fujian Provincial Clinical College, Medical College, Fujian Medical University, Fuzhou, China.|Department of Anaesthesiology, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zheng
authors.affiliation: Fujian Provincial Clinical College, Medical College, Fujian Medical University, Fuzhou, China.|Department of Anaesthesiology, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: Chun-Ying
authors.initials: CY
authors.lastname: Zheng
authors.affiliation: Fujian Provincial Clinical College, Medical College, Fujian Medical University, Fuzhou, China.|Department of Anaesthesiology, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: Xiao-Chun
authors.initials: XC
authors.lastname: Zheng
authors.affiliation: Fujian Provincial Clinical College, Medical College, Fujian Medical University, Fuzhou, China.|Department of Anaesthesiology, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: Ruo-Guang
authors.initials: RG
authors.lastname: Zhao
authors.affiliation: Fujian Provincial Clinical College, Medical College, Fujian Medical University, Fuzhou, China.|Department of Anaesthesiology, Fujian Provincial Hospital, Fujian Medical University, Fuzhou, China.
authors.forename: Yan-Qing
authors.identifier: http://orcid.org/0000-0001-7220-9338
authors.initials: YQ
authors.lastname: Chen
mesh_terms: D000577:Amides / Q000008:administration & dosage*; D000779:Anesthetics, Local / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D006801:Humans; D009243:NAD / Q000008:administration & dosage* / Q000378:metabolism*; D010616:Phenanthrenes / Q000008:administration & dosage; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000077212:Ropivacaine
chemical_list: D000577:Amides; D000779:Anesthetics, Local; C434926:N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride; D010616:Phenanthrenes; D009243:NAD; D000077212:Ropivacaine; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1
keywords: NAD+; PARP-1; neuronal injury; ropivacaine