Effect of body-weight loading onto the articular cartilage on the occurrence of quinolone-induced chondrotoxicity in juvenile rats

Toxicol Lett. 2013 Feb 4;216(2-3):124-9. doi: 10.1016/j.toxlet.2012.11.017. Epub 2012 Nov 29.

Abstract

The effect of body-weight loading onto the articular cartilage on the occurrence of chondrotoxicity was investigated in male juvenile Sprague-Dawley rats given ofloxacin (OFLX) orally once at 900 mg/kg. Just after dosing of OFLX, hindlimb unloading was performed for 0, 2, 4, or 8 h by a tail-suspension method. Animals were sacrificed at 8h post-dose, and then the distal femoral articular cartilage was subjected to a histological examination and an investigation for gene expression of tumor necrosis factor receptor superfamily, member 12a (Tnfrsf12a); prostaglandin-endoperoxide synthase 2 (Ptgs2); plasminogen activator, urokinase receptor (Plaur); and matrix metalloproteinase 3 (Mmp3) by qRT-PCR analysis. As a result, cartilage lesions and up-regulations of these 4 genes that were seen in rats without the tail suspension were not observed in rats with the 8-h tail suspension, and a tendency to decrease in the incidence of the cartilage lesions and the gene expression was noted in a tail-suspension time dependent manner. Our results clearly indicate that body-weight loading onto the cartilage is necessary to induce cartilage lesions and gene expression of Tnfrsf12a, Ptgs2, Plaur, and Mmp3 in juvenile rats treated with OFLX.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / toxicity*
  • Cartilage, Articular / drug effects*
  • Cartilage, Articular / metabolism
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Gene Expression Regulation / drug effects
  • Hindlimb Suspension / methods
  • Histocytochemistry
  • Male
  • Matrix Metalloproteinase 3 / genetics
  • Matrix Metalloproteinase 3 / metabolism
  • Ofloxacin / toxicity*
  • RNA / chemistry
  • RNA / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Real-Time Polymerase Chain Reaction
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / metabolism
  • Receptors, Urokinase Plasminogen Activator / genetics
  • Receptors, Urokinase Plasminogen Activator / metabolism
  • TWEAK Receptor

Substances

  • Anti-Bacterial Agents
  • Receptors, Tumor Necrosis Factor
  • Receptors, Urokinase Plasminogen Activator
  • TWEAK Receptor
  • Tnfrsf12a protein, rat
  • RNA
  • Ofloxacin
  • Cyclooxygenase 2
  • Ptgs2 protein, rat
  • Matrix Metalloproteinase 3