Lidocaine potentiates the chondrotoxicity of methylprednisolone

Arthroscopy. 2009 Apr;25(4):337-47. doi: 10.1016/j.arthro.2009.01.003. Epub 2009 Feb 13.

Abstract

Purpose: This study examined the viability of bovine articular chondrocytes after exposure to methylprednisolone, methylprednisolone with lidocaine, and methylprednisolone in a simulated inflammatory environment.

Methods: Bovine articular chondrocytes were suspended in alginate beads and cultured in Dulbecco's modified Eagle's medium/F-12 for 1 week before experimentation. Suspended chondrocytes were exposed to 0.9% saline solution (negative control), methylprednisolone (4, 8, and 16 mg/mL), methylprednisolone (8 mg/mL) with 1% lidocaine, or methylprednisolone (8 mg/mL) and saline solution in a simulated inflammatory environment (interleukin [IL] 1beta exposure, 10 ng/mL) for 15, 30, and 60 minutes. Flow cytometry was performed 1 day, 4 days, and 7 days after exposure by use of annexin V and propidium iodide to assess chondrocyte viability.

Results: Chondrocyte viability decreased from 84% in saline solution to 62%, 38%, and 2.4% 1 day after 60 minutes of exposure to 4, 8, and 16 mg/mL of methylprednisolone, respectively (n = 7, P < .05). Chondrotoxicity increased with increasing time of exposure to methylprednisolone and with increasing time after exposure. In IL-1beta-activated chondrocytes, viability decreased from 76% in saline solution to 2.9% after 60 minutes of methylprednisolone exposure (8 mg/mL) (n = 4, P < .05). The combination of 8 mg/mL of methylprednisolone and 1% lidocaine further reduced viability to 1.0% after 60 minutes (n = 4, P < .05).

Conclusions: These results show a dose- and time-dependent decrease in chondrocyte viability after exposure to clinically relevant doses of methylprednisolone. The combination of methylprednisolone and lidocaine was toxic, with virtually no cells surviving after treatment. In addition, methylprednisolone did not mitigate the inflammatory effects of IL-1beta; rather, it further potentiated the chondrotoxicity.

Clinical relevance: Intra-articular injections of corticosteroids and local anesthetics are widely used in clinical practice. This in vitro study provides information on the potential effects of these drugs on articular cartilage.

MeSH terms

  • Anesthetics, Local / toxicity
  • Animals
  • Biotransformation
  • Cartilage, Articular / cytology
  • Cartilage, Articular / drug effects*
  • Cattle
  • Cell Survival / drug effects
  • Cells, Cultured
  • Chondrocytes / drug effects*
  • Chondrocytes / metabolism
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Glucocorticoids / toxicity
  • Interleukin-1beta / metabolism
  • Interleukin-1beta / pharmacology
  • Lidocaine / toxicity*
  • Methylprednisolone / toxicity*

Substances

  • Anesthetics, Local
  • Glucocorticoids
  • Interleukin-1beta
  • Lidocaine
  • Methylprednisolone