SHAKIBAEI M, SENDZIK J, SCHAFER-KORTING M, STAHLMANN R; Interscience Conference on Antimicrobial Agents and Chemotherapy (43rd: 2003: Chicago, Ill.).
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2003 Sep 14-17; 43: abstract no. A-520.
Inst. of Anatomy, Berlin, Germany.
BACKGROUND: Fluoroquinolones can cause tendinitis and tendon ruptures. The mechanism of this unusual form of toxicity is still unclear. METHODS: We investigated the possible mechanism that causes tendon damage in an in vitro model with human tendon cells. Tenocytes were cultured for 1, 2, 3 or 4 days as monolayers and incubated with 10, 30, 100 mg ciprofloxacin or levofloxacin / l medium supplemented with 5% FCS. The amount of extracellular matrix-, transmembrane- and signal-proteins and in particular the concentration of matrix-metallo-proteinases (MMPs) and caspase-3 (casp-3), was measured by immunoblotting. In addition, ultrastructural changes were analysed by electron microscopy. RESULTS: Already at the lowest concentration tested (10 mg/l) both quinolones caused a decrease of collagen I, beta1-integrin, vinculin and shc which were intensified at higher concentrations and longer incubation. All changes were more pronounced with ciprofloxacin than with levofloxacin. Interestingly, a time and concentration dependant increase of the matrix degrading MMP-1 and MMP-13 as well as the apoptosis marker casp-3 was found: after 1 day of incubation all concentrations were in the range of controls, after 2 days MMPs were increased more than 2-fold with ciprofloxacin only, and after 4 days of incubation, ciprofloxacin and levofloxacin caused drastic increases of MMP-1 (17- and 10-fold), MMP-13 (12- and 10-fold), and casp-3 (6- and 4-fold) compared to control. The apoptotic changes as indicated by the casp-3 increase were confirmed by electron microscopy. CONCLUSION: Our results confirm that fluoroquinolones cause several changes on matrix proteins and signal proteins, especially of the Map-kinase pathway. Additionally, we were able to prove that fluoroquinolones cause apoptosis in human tenocytes which has to be considered a key event in the pathogenesis of quinolone-induced tendinitis or tendon ruptures.
Publication Types:
Keywords:
- Animals
- Apoptosis
- Caspase 3
- Caspases
- Ciprofloxacin
- Collagen
- Extracellular Matrix
- Fluoroquinolones
- Humans
- In Vitro
- Matrix Metalloproteinase 1
- Matrix Metalloproteinases
- Microscopy, Electron
- Ofloxacin
- Quinolones
- Tendons
Other ID:
UI: 102264660
From Meeting Abstracts