Ciprofloxacin causes cytoskeletal changes and detachment of human and rat chondrocytes in vitro

Arch Toxicol. 2000 Jan;73(10-11):557-63. doi: 10.1007/s002040050008.

Abstract

Quinolones cause damage of articular cartilage in different species by forming chelate complexes with divalent cations and inducing magnesium deficiency. Cations are important for regular function of integrins, a group of transmembrane proteins which connect extracellular matrix proteins with the intracellular cytoskeleton. We have shown that cultivation of rat chondrocytes in ciprofloxacin (CFX)-supplemented and Mg(2+)-free medium led to pronounced changes in the cytoskeleton and decreased adhesion of cells to the culture dish. In order to test whether or not these effects are species-specific, we extended our studies on human chondrocytes. Human chondrocytes cultivated in CFX-supplemented medium (10, 40, 80 and 160 microg/ml) or Mg(2+)-free medium showed decreased ability to adhere to growth support, cell shape changes, and alterations in actin and vimentin cytoskeleton in a concentration dependent manner. Attachment of human chondrocytes to collagen type II coated cover slips was reduced to 90% in CFX group and 75% in Mg(2+)-free group on day 1. This effect even increased after 4 days of culture in the respective medium (32% in CFX and 58% in Mg(2+)-free group). We concluded that Mg(2+) deficiency is exerted via integrins, resulting in decreased ability to attach to extracellular matrix proteins and cytoskeletal changes. These effects are not species-specific. The attachment assay proves to be an easy to use experimental set-up to test ciprofloxacin and other quinolones for their chondrotoxic effects.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Infective Agents / pharmacology*
  • Cartilage, Articular / cytology
  • Cartilage, Articular / drug effects*
  • Cartilage, Articular / physiology
  • Cell Adhesion / drug effects*
  • Cell Adhesion / physiology
  • Cells, Cultured
  • Chondrocytes / drug effects*
  • Chondrocytes / physiology
  • Ciprofloxacin / pharmacology*
  • Collagen / pharmacology
  • Culture Media
  • Cytoskeleton / drug effects*
  • Cytoskeleton / physiology
  • Humans
  • Magnesium / pharmacology
  • Microscopy, Confocal
  • Rats
  • Species Specificity

Substances

  • Anti-Infective Agents
  • Culture Media
  • Ciprofloxacin
  • Collagen
  • Magnesium