title: OGG1 Involvement in High Glucose-Mediated Enhancement of Bupivacaine-Induced Oxidative DNA Damage in SH-SY5Y Cells.
abstract: Hyperglycemia can inhibit expression of the 8-oxoG-DNA glycosylase (OGG1) which is one of the key repair enzymes for DNA oxidative damage. The effect of hyperglycemia on OGG1 expression in response to local anesthetics-induced DNA damage is unknown. This study was designed to determine whether high glucose inhibits OGG1 expression and aggravates bupivacaine-induced DNA damage via reactive oxygen species (ROS). SH-SY5Y cells were cultured with or without 50 mM glucose for 8 days before they were treated with 1.5 mM bupivacaine for 24 h. OGG1 expression was measured by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. ROS was estimated using the redox-sensitive fluorescent dye DCFH-DA. DNA damage was investigated with immunostaining for 8-oxodG and comet assays. OGG1 expression was inhibited in cells exposed to high glucose with concomitant increase in ROS production and more severe DNA damage as compared to control culture conditions, and these changes were further exacerbated by bupivacaine. Treatment with the antioxidant N-acetyl-L-cysteine (NAC) prevented high glucose and bupivacaine mediated increase in ROS production and restored functional expression of OGG1, which lead to attenuated high glucose-mediated exacerbation of bupivacaine neurotoxicity. Our findings indicate that subjects with diabetes may experience more detrimental effects following bupivacaine use.
authors.affiliation: Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, No. 253 Middle Gongye Street, Guangzhou, Guangdong 510282, China.
authors.forename: Zhong-Jie
authors.initials: ZJ
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, No. 253 Middle Gongye Street, Guangzhou, Guangdong 510282, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, No. 253 Middle Gongye Street, Guangzhou, Guangdong 510282, China.
authors.forename: Qing-Guo
authors.initials: QG
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, No. 253 Middle Gongye Street, Guangzhou, Guangdong 510282, China.
authors.forename: Le
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, No. 253 Middle Gongye Street, Guangzhou, Guangdong 510282, China.
authors.forename: Lu-Ying
authors.initials: LY
authors.lastname: Lai
authors.affiliation: Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, No. 253 Middle Gongye Street, Guangzhou, Guangdong 510282, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, No. 253 Middle Gongye Street, Guangzhou, Guangdong 510282, China.
authors.forename: Shi-Yuan
authors.initials: SY
authors.lastname: Xu
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000111:Acetylcysteine / Q000494:pharmacology; D002045:Bupivacaine / Q000633:toxicity*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; D003849:Deoxyguanosine; D005947:Glucose; D000111:Acetylcysteine; D002045:Bupivacaine