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Neurochemical Research

, Volume 40, Issue 9, pp 1919–1928 | Cite as

Increased Oxidative Damage and Reduced DNA Repair Enzyme XPD Involvement in High Glucose-Mediated Enhancement of Levobupivacaine-Induced Neurotoxicity

  • ZhongJie Liu
  • Wei Zhao
  • QingGuo Zhang
  • LuYing Lai
  • Shan Jiang
  • Jing Zhang
  • ShiYuan XuEmail author
Original Paper

Abstract

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.

Keywords

XPD High glucose Neurotoxicity Levobupivacaine SH-SY5Y cells 

Abbreviations

XPD

Xeroderma pigmentosum complementation group D

NER

Nucleotide excision repair

OTM

Olive tail moment

Notes

Acknowledgments

This study was supported by the National Science Foundation of China (Grant No. 81271390) and Natural Science Foundation for the Youth (Grant No. 81400995). None of the authors have financial relationships with biotechnology manufacturers, pharmaceutical companies, or other commercial entities with an interest in the subject matter or materials discussed in the manuscripts.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • ZhongJie Liu
    • 1
  • Wei Zhao
    • 1
  • QingGuo Zhang
    • 1
  • LuYing Lai
    • 1
  • Shan Jiang
    • 1
  • Jing Zhang
    • 1
  • ShiYuan Xu
    • 1
    Email author
  1. 1.Department of Anesthesiology, Zhujiang HospitalSouthern Medical UniversityGuangzhouChina

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