title: Bupivacaine induces apoptosis via ROS in the Schwann cell line.
abstract: Local anesthetics have been generally accepted as being safe. However, recent clinical trials and basic studies have provided strong evidence for the neurotoxicity of local anesthetics, especially through apoptosis. We hypothesized that local anesthetics cause neural complications through Schwann cell apoptosis. Among local anesthetics tested on the Schwann cell line, RT4-D6P2T, bupivacaine significantly induced cell death, measured by the methyl tetrazolium (MTT) assay, in a dose- (LD50 = 476 microM) and time-dependent manner. The bupivacaine-induced generation of reactive oxygen species (ROS), which was initiated within 5 hrs and preceded the activation of caspase-3 and poly ADP-ribose polymerase (PARP) degradation, was suggested to trigger apoptosis, exhibited by Hoechst 33258 nuclear staining and DNA fragmentation. Furthermore, concomitant block of ROS by anti-oxidants significantly inhibited bupivacaine-induced apoptosis. Among the local anesthetics for peripheral neural blocks, bupivacaine induced apoptosis in the Schwann cell line, which may be associated with ROS production.
authors.affiliation: Department of Dental Anesthesiology and Dental Research Institute, Seoul National University College of Dentistry, 28 Yongon-dong Chongno-gu, Seoul 110-744, Korea.
authors.forename: C J
authors.initials: CJ
authors.lastname: Park
authors.forename: S A
authors.initials: SA
authors.lastname: Park
authors.forename: T G
authors.initials: TG
authors.lastname: Yoon
authors.forename: S J
authors.initials: SJ
authors.lastname: Lee
authors.forename: K W
authors.initials: KW
authors.lastname: Yum
authors.forename: H J
authors.initials: HJ
authors.lastname: Kim
mesh_terms: D000704:Analysis of Variance; D000779:Anesthetics, Local / Q000633:toxicity*; D017209:Apoptosis; D015153:Blotting, Western; D002045:Bupivacaine / Q000633:toxicity*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D005456:Fluorescent Dyes; D006801:Humans; D009569:Nitric Oxide / Q000032:analysis; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000032:analysis*; D012583:Schwann Cells / Q000187:drug effects*; D018709:Statistics, Nonparametric
chemical_list: D000779:Anesthetics, Local; D005456:Fluorescent Dyes; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D002045:Bupivacaine