Nicotinamide Adenine Dinucleotide (NAD+) Repletion Attenuates Bupivacaine-Induced Neurotoxicity
Nicotinamide Adenine Dinucleotide (NAD+) Repletion Attenuates Bupivacaine-Induced Neurotoxicity
复制标题
DOI：
10.1007/s11064-013-1094-0
复制
发表时间：
2013-07
影响因子：
4.4
通讯作者：
Ting Zheng;Shiyuan Xu;Shu‐qin Zhou;Luying Lai;Le Li
中科院分区：
文献类型：
--
作者：
Ting Zheng;Shiyuan Xu;Shu‐qin Zhou;Luying Lai;Le Li
Bupivacaine is one of the most toxic local anesthetics but the mechanisms underlying its neurotoxicity are still unclear. Intracellular nicotinamide adenine dinucleotide (NAD+) depletion has been demonstrated to play an essential role in neuronal injury. In the present study, we investigated whether intracellular NAD+depletion contributes to bupivacaine-induced neuronal injury and whether NAD+repletion attenuates the injury in SH-SY5Y cells. First, we evaluated the intracellular NAD+content after bupivacaine exposure. We also examined the cellular NAD+level after pretreatment with exogenous NAD+. We next determined cell viability and the apoptosis rate after bupivacaine treatment in the presence or absence of NAD+incubation. Finally, cell injuries such as nuclear injury, reactive oxygen species (ROS) production, and mitochondrial depolarization were detected after bupivacaine treatment with or without NAD+pretreatment. Bupivacaine caused intracellular NAD+depletion in a time- and concentration-dependent manner. Cellular NAD+replenishment prevented cell death and apoptosis induced by bupivacaine. Importantly, exogenous NAD+attenuated bupivacaine-induced nuclear injury, ROS production, and mitochondrial depolarization. Our results suggest that NAD+depletion is necessary for bupivacaine-induced neuronal necrosis and apoptosis, and that NAD+repletion attenuates neurotoxicity resulting from bupivacaine-treatment.
