Fluoroquinolones cause changes in extracellular matrix, signalling proteins, metalloproteinases and caspase-3 in cultured human tendon cells

Sendzik, Judith; Shakibaei, Mehdi; Schäfer‐Korting, Monika; Stahlmann, Ralf

doi:10.1016/j.tox.2005.04.002

Cited by 99 publications

(83 citation statements)

References 30 publications

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“…In a previous publication we have described that the quinolones ciprofloxacin and levofloxacin caused a time-and concentration-dependent decline in extracellular matrix and key signalling proteins in human tenocytes in vitro [25]. Furthermore, an increase in the apoptosis marker activated caspase-3 as well as characteristic ultrastructural degenerative features were observed in the quinolone-treated tenocytes.…”

Section: Discussionmentioning

confidence: 83%

“…A time-and concentration-dependent increase in caspase-3 was observed following incubation with the quinolones [25]. In comparison with incubation with 0.1 nM dexamethasone alone, combined exposure of the cells to 3 mg/L of either ciprofloxacin or levofloxacin plus 0.1 nM dexamethasone increased the concentration of caspase-3 from Day 3 onwards (Fig.…”

Section: Activation Of Caspase-3mentioning

confidence: 82%

“…We found changes in the extracellular matrix, 1 -integrin receptors as well as in signalling proteins of the MAP kinase pathway. In addition, probably as a consequence of the cell-cell and cellmatrix disturbance, apoptosis was induced in human tenocytes at concentrations of quinolones that are achieved in human plasma and tissues during therapy with these drugs [25].…”

Section: Page 5 Of 37mentioning

confidence: 99%

“…Finger tendon explants obtained during surgery were used to isolate primary human tenocytes [25]. Briefly, following non-enzymatic isolation, cells were expanded in monolayers and multiplied.…”

Section: Cell Culturementioning

confidence: 99%

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Synergistic effects of dexamethasone and quinolones on human-derived tendon cells

Sendzik

Shakibaei

Schäfer‐Korting

et al. 2010

International Journal of Antimicrobial Agents

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Quinolones and glucocorticoids are frequently used drugs that may cause tendinopathy as a rare adverse effect. We exposed human tenocyte cultures to the steroid dexamethasone alone or in combination with either ciprofloxacin or levofloxacin at concentrations of 3 mg/L and 10 mg/L. At concentrations corresponding to peak levels in plasma and tissues during therapy (ca. 3-10 mg/L), ciprofloxacin caused a significant decrease in collagen type I and the 1 -integrin receptor. In contrast, no corresponding effect was induced by 3 mg/L levofloxacin.With both quinolones at 3 mg/L and 10 mg/L, the amount of matrix metalloproteinase-1 (MMP-1) and MMP-13 was increased. In addition, 3 mg/L ciprofloxacin and 10 mg/L levofloxacin activated caspase-3. Apoptotic changes were confirmed by electron microscopy. Incubation of human tenocytes with dexamethasone decreased the main matrix protein collagen type I, the

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Section: Discussionmentioning

confidence: 83%

Section: Activation Of Caspase-3mentioning

confidence: 82%

Section: Page 5 Of 37mentioning

confidence: 99%

Section: Cell Culturementioning

confidence: 99%

See 2 more Smart Citations

Synergistic effects of dexamethasone and quinolones on human-derived tendon cells

Sendzik

Shakibaei

Schäfer‐Korting

et al. 2010

International Journal of Antimicrobial Agents

Self Cite

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“…Frequent contact of the bacteria with even minor concentrations of antibiotics can cause the occurrence or persistence of resilient bacteria strains [17][18][19][20][21]. Earlier research showed that the maximum of the antibiotics in the environment showed straight hazardous properties [22,23] and bad effects [24][25][26].…”

Section: Sources Of Antibiotics In the Environmentmentioning

confidence: 99%

Estimation of Residual Antibiotics in Pharmaceutical Effluents and their Fate in Affected Areas

Hussain

Naeem

Chaudhry

2016

Pol. J. Environ. Stud.

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Assessing the potential of pharmaceuticals and their transformation products to cause mutagenic effects: Implications for gene expression profiling

Vasquez

Tarapoulouzi

Lambrianides

et al. 2016

Enviro Toxic and Chemistry

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The selection and prioritization of pharmaceuticals and their transformation products for evaluating effects on the environment and human health is a challenging task. One common approach is based on compounds (e.g., mixture composition, concentrations), and another on biology (e.g., relevant endpoint, biological organizational level). Both of these approaches often resemble a Lernaean Hydra-they can create more questions than answers. The present study embraces this complexity, providing an integrated approach toward assessing the potential effects of transformation products of pharmaceuticals by means of mutagenicity, estrogenicity, and differences in the gene expression profiles. Mutagenicity using the tk kinase assay was applied to assess a list of 11 priority pharmaceuticals, namely, atenolol, azithromycin, carbamazepine, diclofenac, ibuprofen, erythromycin, metoprolol, ofloxacin, propranolol, sulfamethoxazole, and trimethoprim. The most mutagenic compounds were found to be β-blockers. In parallel, the photolabile pharmaceuticals were assessed for their mixture effects on mutagenicity (tk assay), estrogenicity (T47D- KBluc assay), and gene expression (microarrays). Interestingly, the mixtures were mutagenic at the µg/L level, indicating a synergistic effect. None of the photolysed mixtures were statistically significantly estrogenic. Gene expression profiling revealed effects related mainly to certain pathways, those of the p53 gene, mitogen-activated protein kinase, alanine, aspartate, and glutamate metabolism, and translation-related (spliceosome). Fourteen phototransformation products are proposed based on the m/z values found through ultra-performance liquid chromatography-tandem mass spectrometry analysis. The transformation routes of the photolysed mixtures indicate a strong similarity with those obtained for each pharmaceutical separately. This finding reinforces the view that transformation products are to be expected in naturally occurring mixtures. Environ Toxicol Chem 2016;35:2753-2764. © 2016 SETAC.

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Fluoroquinolones cause changes in extracellular matrix, signalling proteins, metalloproteinases and caspase-3 in cultured human tendon cells

Cited by 99 publications

References 30 publications

Synergistic effects of dexamethasone and quinolones on human-derived tendon cells

Synergistic effects of dexamethasone and quinolones on human-derived tendon cells

Estimation of Residual Antibiotics in Pharmaceutical Effluents and their Fate in Affected Areas

Assessing the potential of pharmaceuticals and their transformation products to cause mutagenic effects: Implications for gene expression profiling

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