Neurotoxicity Comparison of Two Types of Local Anaesthetics: Amide-Bupivacaine versus Ester-Procaine.
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.
Zhujiang Hospital, Southern Medical University, Guangzhou City, China.
Xu-Jiao
XJ
Yu
Zhujiang Hospital, Southern Medical University, Guangzhou City, China.
Wei
W
Zhao
Zhujiang Hospital, Southern Medical University, Guangzhou City, China.
Yu-Jie
YJ
Li
Zhujiang Hospital, Southern Medical University, Guangzhou City, China.
Feng-Xian
FX
Li
Zhujiang Hospital, Southern Medical University, Guangzhou City, China.
Zhong-Jie
ZJ
Liu
Zhujiang Hospital, Southern Medical University, Guangzhou City, China.
Hua-Li
HL
Xu
Zhujiang Hospital, Southern Medical University, Guangzhou City, China.
Lu-Ying
LY
Lai
Zhujiang Hospital, Southern Medical University, Guangzhou City, China.
Rui
R
Xu
Zhujiang Hospital, Southern Medical University, Guangzhou City, China.
Shi-Yuan
SY
Xu
D000577:Amides / Q000737:chemistry; D000779:Anesthetics, Local / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002045:Bupivacaine / Q000737:chemistry / Q000633:toxicity*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000187:drug effects; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011343:Procaine / Q000737:chemistry / Q000633:toxicity*; D017382:Reactive Oxygen Species
D000577:Amides; D000779:Anesthetics, Local; D017382:Reactive Oxygen Species; D011343:Procaine; D053148:Caspase 3; D053453:Caspase 9; D002045:Bupivacaine