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Selected Publication:

Type of publication: Journal Article
Type of document: Full Paper

Year: 2000

Authors: Egerbacher, M; Seiberl, G; Wolfesberger, B; Walter, I

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

Source: Arch Toxicol. 2000; 73(10-11):557-563



Authors Vetmeduni Vienna:

Egerbacher Monika
Walter Ingrid
Wolfesberger Birgitt

Vetmed Research Units
Institute of Topographical Anatomy


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.

Keywords Pubmed: 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

Keywords:


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