Cytotoxic effects of the quinolone levofloxacin on rabbit meniscus cells

J Appl Toxicol. 2014 Aug;34(8):870-7. doi: 10.1002/jat.2903. Epub 2013 Jul 1.


Quinolones have been reported to induce adverse effects on articular cartilage, tendons and ligaments. However, the effects of quinolones on menisci have not been revealed. The present study was to test the effects of levofloxacin on meniscus cells in vitro. Rabbit meniscus cells were administrated with different concentrations of levofloxacin (0, 14, 28, 56, 112 and 224 µm) for 24 or 48 h, and cell viability and apoptosis were measured. The mRNA expression levels of matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, tissue inhibitors of metalloproteinase (TIMP)-1, TIMP-3, Col1a1, Bcl-2, caspase-3 and inducible nitric oxide were analyzed by real-time polymerase chain reaction. Active caspase-3 was detected by immunocytochemical assay, while protein expression levels of MMP-3 and MMP-13 were measured by Western blotting assay. After treatment with levofloxacin for 48 h, cell viability was decreased from dose of 28 to 224 µm in a concentration-dependent manner. An increase of apoptotic cells was observed by flow cytometry. Active caspase-3 protein expression level was also increased. The mRNA level of Bcl-2 was decreased and levels of MMP-1, MMP-3 and MMP-13 in experimental groups were higher than those of controls. The protein levels of MMP-3 and MMP-13 were increased. Moreover, the mRNA levels of TIMP-3 and col1a1 were decreased. A dose-dependent increase of inducible nitric oxide mRNA expression level was also observed. Our results suggested the cytotoxic effects of levofloxacin on meniscus cells through induction of apoptosis and unbalanced MMPs/TIMPs expression. These side effects might result in meniscus extracellular matrix degradation and meniscal lesion. Thus, quinolones should be used cautiously on patients who perform athletic activities or undergo surgical meniscus repair.

Keywords: apoptosis; extracellular matrix degradation; levofloxacin; matrix metalloproteinases; meniscus cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cartilage
  • Cell Survival / drug effects
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Gene Expression Regulation
  • Levofloxacin / pharmacology*
  • Matrix Metalloproteinase 1 / genetics
  • Matrix Metalloproteinase 1 / metabolism
  • Matrix Metalloproteinase 13 / genetics
  • Matrix Metalloproteinase 13 / metabolism
  • Matrix Metalloproteinase 3 / genetics
  • Matrix Metalloproteinase 3 / metabolism
  • Menisci, Tibial / cytology*
  • Menisci, Tibial / drug effects*
  • Menisci, Tibial / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rabbits
  • Real-Time Polymerase Chain Reaction
  • Tissue Inhibitor of Metalloproteinase-1 / genetics
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Tissue Inhibitor of Metalloproteinase-3 / genetics
  • Tissue Inhibitor of Metalloproteinase-3 / metabolism
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism


  • Collagen Type I
  • RNA, Messenger
  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinase-3
  • bcl-2-Associated X Protein
  • Levofloxacin
  • Matrix Metalloproteinase 13
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 1