title: N-acetyl cysteine protects cells from chondrocyte death induced by local anesthetics.
abstract: Local anesthetics (LA) are among the drugs most frequently used for musculoskeletal problems, in procedures ranging from diagnosis to postoperative pain control. Chondrocyte toxicity induced by LA is an emerging area of concern. The purpose of this study was to determine whether N-acetyl cysteine (NAC), an antioxidant, will exert cytoprotective effects against chondrocyte death induced by LA. Primary cultured human chondrocytes were used for this study. This study used control, NAC, LA, and NAC-LA groups. Cytotoxicity was induced in the LA subgroups and their paired NAC-LA subgroups through exposure to ropivacaine (0.075%), bupivacaine (0.05%), or lidocaine (0.2%) for 24 h. The NAC-LA subgroups were exposed to 10 mM NAC for 1 h, before LA exposure. These study groups were evaluated for rates of cell viability, apoptosis, necrosis, intracellular ROS production, and caspase-3/7 activity. Cell viability in all LA subgroups was significantly lower than in the control group (p < 0.001). Cell viability in the NAC-LA subgroups was significantly higher than in their paired LA subgroups (p < 0.001). In the LA subgroups, rates of apoptosis and necrosis, intracellular ROS production, and caspase-3/7 activity were significantly higher than in the control group (p ≤ 0.029). In the NAC-LA subgroups, rates of apoptosis and necrosis, intracellular ROS production, and caspase-3/7 activity were significantly lower than in their paired LA subgroups (p ≤ 0.023). These results indicate that N-acetyl cysteine, an antioxidant, has cytoprotective effects against LA-induced toxicity to chondrocytes in vitro. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:297-303, 2017.
authors.affiliation: Department of Convergence Medical Science, Gyeongsang National University, Jinju, Korea.
authors.forename: Ra Jeong
authors.initials: RJ
authors.lastname: Kim
authors.affiliation: Namhae Garlic Research Institute, Namhae, Korea.
authors.forename: Jae-Ran
authors.initials: JR
authors.lastname: Kang
authors.affiliation: Clinical Research Institute, Gyeongsang National University Hospital, Jinju, Korea.
authors.forename: Young-Sool
authors.initials: YS
authors.lastname: Hah
authors.affiliation: Department of Orthopaedic Surgery and Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, Korea.
authors.forename: Hyung Bin
authors.initials: HB
authors.lastname: Park
mesh_terms: D000111:Acetylcysteine / Q000627:therapeutic use*; D000779:Anesthetics, Local / Q000009:adverse effects*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D019902:Chondrocytes / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D006801:Humans; D061251:Primary Cell Culture; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000779:Anesthetics, Local; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D053148:Caspase 3; D053179:Caspase 7; D000111:Acetylcysteine
keywords: N-acetyl cysteine; antioxidant; chondrocyte; cytotoxicity; local anesthetics