title: Bupivacaine and levobupivacaine induce apoptosis in rat chondrocyte cell cultures at ultra-low doses.
abstract: OBJECTIVE
  Osteoarthritis (OA) is characterized by chondrocyte apoptosis and necrosis which play a key role during the progression of OA. Intra-articular administration of bupivacaine is a practical and effective way of postoperative pain control following various joint surgeries. 0.25 % bupivacaine showed to be safe in terms of chondrocyte toxicity. Around 200 nM of bupivacaine was shown to be effective for peripheral nerve block. This study aims to observe the possible cytotoxic effects of bupivacaine and its enantiomer levobupivacaine on chondrocyte cell culture at 7.69, 76.9, and 384.5 μM or at 0.0125, 0.0025, and 0.00025 % concentrations, respectively.
  
  
  METHODS
  Chondrocytes were isolated from rat articular cartilage after incubating with collagenase in RPMI-1640 medium. Cells were treated with bupivacaine and levobupivacaine at 7.69, 76.9, and 384.5 μM concentrations for 6, 24, and 48 h. Treated chondrocytes were stained with acridine orange and ethidium bromide and examined under a fluorescence microscope at a 490 nm excitation wavelength for apoptotic changes.
  
  
  RESULTS
  Study results suggest that both bupivacaine and levobupivacaine have dose-dependent chondrocyte toxicity, and this is significantly lesser at 7.69 μM dose. There was no significant difference in terms of chondrocyte apoptosis, (p > 0.05).
  
  
  CONCLUSIONS
  Clinicians should be skeptic for the serious long-term side effects of bupivacaine and its analogs, even at ultra-low doses.
authors.affiliation: Department of Anesthesiology and Reanimation, Faculty of Medicine, Gazi University, Ankara, Turkey.
authors.forename: Irfan
authors.initials: I
authors.lastname: Gungor
authors.forename: Akin
authors.initials: A
authors.lastname: Yilmaz
authors.forename: Akif Muhtar
authors.initials: AM
authors.lastname: Ozturk
authors.forename: Mehmet Ali
authors.initials: MA
authors.lastname: Ergun
authors.forename: Sevda
authors.initials: S
authors.lastname: Menevse
authors.forename: Kadir
authors.initials: K
authors.lastname: Kaya
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002045:Bupivacaine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000166:cytology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000502:physiology*; D000077554:Levobupivacaine; D051381:Rats
chemical_list: D000779:Anesthetics, Local; D000077554:Levobupivacaine; D002045:Bupivacaine