Zhujiang Hospital, Southern Medical University, Guangzhou City, China.
Sci Rep. 2017 Mar 24;7:45316. doi: 10.1038/srep45316.
Local anaesthetics (LAs) may lead to neurological complications, but the underlying mechanism is still unclear. Many neurotoxicity research studies have examined different LAs, but none have comprehensively explored the distinct mechanisms of neurotoxicity caused by amide- (bupivacaine) and ester- (procaine) type LAs. Here, based on a CCK8 assay, LDH assay, Rhod-2-AM and JC-1 staining, 2',7'-dichlorohy-drofluorescein diacetate and dihydroethidium probes, an alkaline comet assay, and apoptosis assay, we show that both bupivacaine and procaine significantly induce mitochondrial calcium overload and a decline in the mitochondrial membrane potential as well as overproduction of ROS, DNA damage and apoptosis (P < 0.05). There were no significant differences in mitochondrial injury and apoptosis between the bupivacaine and procaine subgroups (P > 0.05). However, to our surprise, the superoxide anionic level after treatment with bupivacaine, which leads to more severe DNA damage, was higher than the level after treatment with procaine, while procaine produced more peroxidation than bupivacaine. Some of these results were also affirmed in dorsal root ganglia neurons of C57 mice. The differences in the superoxidation and peroxidation induced by these agents suggest that different types of LAs may cause neurotoxicity via different pathways. We can target more accurate treatment based on their different mechanisms of neurotoxicity.
局部麻醉剂（LAs）可能导致神经并发症，但潜在机制尚不清楚。许多神经毒性研究已经研究了不同的 LAs，但没有一项研究全面探讨酰胺型（布比卡因）和酯型（普鲁卡因）LAs 引起的神经毒性的不同机制。在这里，基于 CCK8 测定、LDH 测定、Rhod-2-AM 和 JC-1 染色、2'，7'-二氯氢荧光素二乙酸酯和二氢乙啶探针、碱性彗星试验和凋亡试验，我们表明布比卡因和普鲁卡因都显著诱导线粒体钙超载和线粒体膜电位下降，以及 ROS、DNA 损伤和凋亡的过度产生（P<0.05）。布比卡因和普鲁卡因亚组之间的线粒体损伤和凋亡没有显著差异（P>0.05）。然而，令我们惊讶的是，导致更严重 DNA 损伤的布比卡因处理后的超氧阴离子水平高于普鲁卡因处理后的水平，而普鲁卡因产生的过氧化作用多于布比卡因。在 C57 小鼠背根神经节神经元中也证实了部分这些结果。这些药物引起的超氧化和过氧化的差异表明，不同类型的 LAs 可能通过不同的途径引起神经毒性。我们可以根据它们不同的神经毒性机制进行更准确的靶向治疗。
