Park C J, Park S A, Yoon T G, Lee S J, Yum K W, Kim H J
Department of Dental Anesthesiology and Dental Research Institute, Seoul National University College of Dentistry, 28 Yongon-dong Chongno-gu, Seoul 110-744, Korea.
J Dent Res. 2005 Sep;84(9):852-7. doi: 10.1177/154405910508400914.
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.
局部麻醉剂通常被认为是安全的。然而，最近的临床试验和基础研究提供了强有力的证据，证明局部麻醉剂具有神经毒性，尤其是通过细胞凋亡产生的神经毒性。我们推测局部麻醉剂通过施万细胞凋亡导致神经并发症。在对施万细胞系RT4-D6P2T进行测试的局部麻醉剂中，布比卡因通过甲基四氮唑（MTT）法检测，以剂量（半数致死剂量LD50 = 476微摩尔）和时间依赖性方式显著诱导细胞死亡。布比卡因诱导的活性氧（ROS）生成在5小时内开始，并先于半胱天冬酶-3的激活和聚ADP-核糖聚合酶（PARP）的降解，这被认为触发了凋亡，通过Hoechst 33258核染色和DNA片段化得以体现。此外，抗氧化剂对ROS的同时阻断显著抑制了布比卡因诱导的凋亡。在外周神经阻滞用的局部麻醉剂中，布比卡因诱导施万细胞系凋亡，这可能与ROS产生有关。
