title: Lidocaine cytotoxicity to the bovine articular chondrocytes in vitro: changes in cell viability and proteoglycan metabolism.
abstract: OBJECTIVE
  A lot of studies on the effect of intra-articular injections are clinical, but many questions on the effect of lidocaine to articular chondrocytes remain unanswered. This study was performed to determine the effects of varying concentrations and exposure times of lidocaine on the viability and proteoglycan metabolism of chondrocytes in vitro.
  
  
  METHODS
  Cartilage was obtained from metatarsal joints of adult bovines. Chondrocytes in alginate beads were cultured in medium containing 6% fetal calf serum at 370 mOsmol at cell densities of 4 million cells/ml. They were then cultured for 24 h under 21% oxygen with 0.125, 0.25, 0.5, and 1% lidocaine and without lidocaine as control. The cell viability profile across intact beads was determined by manual counting using fluorescent probes and transmission electron microscopy.
  
  
  RESULTS
  Lactate production was measured enzymatically as a marker of energy metabolism. Glycosaminoglycan (GAG) accumulation was measured using a modified dimethylmethylene blue assay. Cell viability decreased in a time- and dose-dependent manner in the concentration range of 0.125-1.0% lidocaine under the confocal microscope. Under the electron microscope, apoptosis increased as the concentration of lidocaine increased. GAG accumulation/tissue volume decreases as the concentration of lidocaine increased. However, GAG produced per million cells and the rate of lactate production per live cell were significantly higher for cells cultured at 0.5 and 1% lidocaine than the control group. Bovine chondrocytes cultured in alginate beads under high oxygen pressure are negatively influenced by increasing concentrations of lidocaine.
  
  
  CONCLUSIONS
  Cell viability and proteoglycan production (GAG accumulation/tissue volume) decreased as the concentration of lidocaine increased. These data suggest caution in prolonged exposure of cartilage to high concentration lidocaine. Repeated joint injection of lidocaine potentially worsens osteoarthrosis by accelerating cartilage degradation.
authors.affiliation: Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical Sciences, The University of Fukui, Shimoaizuki 23, Matsuoka, Fukui 910-1193, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Kenichi
authors.initials: K
authors.lastname: Takeno
authors.forename: Takafumi
authors.initials: T
authors.lastname: Yayama
authors.forename: Adam
authors.initials: A
authors.lastname: Meir
authors.forename: Hisatoshi
authors.initials: H
authors.lastname: Baba
mesh_terms: D000779:Anesthetics, Local / Q000633:toxicity*; D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects*; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006025:Glycosaminoglycans / Q000378:metabolism*; D066298:In Vitro Techniques; D019344:Lactic Acid / Q000378:metabolism; D008012:Lidocaine / Q000633:toxicity*; D008297:Male; D008684:Metatarsus; D046529:Microscopy, Electron, Transmission; D011509:Proteoglycans / Q000378:metabolism*; D013997:Time Factors
chemical_list: D000779:Anesthetics, Local; D006025:Glycosaminoglycans; D011509:Proteoglycans; D019344:Lactic Acid; D008012:Lidocaine