Increased Oxidative Damage and Reduced DNA Repair Enzyme XPD Involvement in High Glucose-Mediated Enhancement of Levobupivacaine-Induced Neurotoxicity.
Levobupivacaine is one of the major clinical local anesthetics, but it can cause neuron toxic damage. Hyperglycemia can cause neuronal DNA oxidative damage and inhibit expression of the DNA repair gene Xeroderma pigmentosum complementation group D (XPD). This study was designed to determine whether high glucose levels inhibit XPD expression and enhance levobupivacaine-induced DNA damage. We evaluated XPD mRNA and protein expression in SH-SY5Y cells after glucose and levobupivacaine exposure. We next investigated cells reactive oxygen species (ROS) levels, DNA damage and apoptosis with redox-sensitive fluorescent dye DCFH-DA (2',7'-dichlorofluorescein diacetate), comet assays, flow cytometry, and TUNEL (terminal deoxynucleotidyl transferased UTP nick end labeling) assays. XPD expression was inhibited in cells exposed to prolonged high glucose with a concomitant increase in ROS production and more severe DNA damage compared to control culture conditions, and these changes were further exacerbated by levobupivacaine. Our findings indicate that subjects with diabetes may experience more detrimental effects following local anesthetic use.
Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, 253 Industrial Road, Guangzhou, 510282, Guangdong Province, China.
ZhongJie
Z
Liu
Wei
W
Zhao
QingGuo
Q
Zhang
LuYing
L
Lai
Shan
S
Jiang
Jing
J
Zhang
ShiYuan
S
Xu
D000779:Anesthetics, Local / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D002045:Bupivacaine / Q000031:analogs & derivatives* / Q000633:toxicity; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D004249:DNA Damage; D004260:DNA Repair; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000008:administration & dosage*; D006801:Humans; D000077554:Levobupivacaine; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D051759:Xeroderma Pigmentosum Group D Protein / Q000378:metabolism*
D000779:Anesthetics, Local; D017382:Reactive Oxygen Species; D000077554:Levobupivacaine; D053453:Caspase 9; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human; D005947:Glucose; D002045:Bupivacaine