The effects of levofloxacin on rabbit fibroblast-like synoviocytes in vitro

Tan, Yang; Lu, Kaihang; Deng, Yu; Cao, Hong; Chen, Biao; Wang, Hui; Magdalou, Jacques; Chen, Liaobin

doi:10.1016/j.taap.2012.10.003

Cited by 18 publications

(10 citation statements)

References 31 publications

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“…Previous studies showed that when combined with IL-1β, ciprofloxacin could increase the expression of MMPs in human tendon cells after being incubated with ciprofloxacin at a concentration of 150 μM (50 μg/ml) for 48 h, but in the absence of IL-1β, ciprofloxacin caused no significant effects on the expression of certain MMPs, even at a high concentration [ 10 , 15 ]. In another study, levofloxacin was found to significantly increase the mRNA expression of MMP-3 and MMP-13 in a concentration-dependent manner, even at the low concentration of 14 μM without IL-1β [ 8 ], which was in line with the result in our study that levofloxacin showed similar cytotoxicity on RAF cells. These above-mentioned results seem to indicate that ACL (anterior cruciate ligament) cells and AF cells are more susceptible to cytotoxicity by fluoroquinolones than tendon cells or that levofloxacin is more cytotoxic than ciprofloxacin.…”

Section: Discussionsupporting

confidence: 92%

“…Sode’s research indicated that quinolone use might triple the risk of Achilles tendon rupture [ 7 ]. Recent studies showed that levofloxacin could trigger cytotoxic effects on anterior cruciate ligament and fibroblast-like synoviocytes of rabbits [ 2 , 8 , 9 ]. The mechanism of toxic effects of fluoroquinolones on tendon cells in vitro has been well defined [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

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Toxic Effects of Levofloxacin on Rat Annulus Fibrosus Cells: An In-vitro Study

et al. 2014

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BackgroundFluoroquinolones are in wide clinical use as safe and effective antibiotics. Articular cartilage, tendons, and epiphyseal growth plates have been recognized as targets of fluoroquinolone-induced connective tissue toxicity. However, the effects of fluoroquinolones on annulus fibrosus (AF) cells are still unknown.Material/MethodsThe main objective of this study was to investigate the effects of levofloxacin, a typical fluoroquinolone antibiotic drug, on rat AF cells in vitro. Rat annulus fibrosus (RAF) cells were treated with levofloxacin at different concentrations (0, 10, 20, 30, 40, 60, 80, and 90 μg/ml) and were assessed to determine the possible cytotoxic effects of levofloxacin. Inverted phase-contrast microscopy was used to accomplish the morphological observation of apoptosis of treated cells. Western blot and real-time quantitative RT-PCR (qPCR) was used to explore the expression of active caspase-3 and MMP-3. Flow cytometry was used to measure the apoptotic incidences.ResultsOur study showed that levofloxacin, with concentrations at 30, 60, and 90 μg/ml, induced dose-dependent RAF cell apoptosis and higher expression of caspase-3 and MMP-3. More apoptotic cells were observed by inverted phase-contrast microscopy. Moreover, levofloxacin increased the activity of caspase-3, and it also reduced cell viability with different concentrations ranging from 10 to 80 μg/ml.ConclusionsOur study results suggest that levofloxacin has cytotoxic effects on RAF cells, characterized by enhancing apoptosis and reducing cell viability, and indicate a potential toxic effect of fluoroquinolones on RAF cells.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Toxic Effects of Levofloxacin on Rat Annulus Fibrosus Cells: An In-vitro Study

et al. 2014

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“…Zn was therefore added to Cd-treated cultures to clarify its possible enhancing or competitive effect on cell viability and inflammation. Zn addition partially reversed the effect of Cd on synoviocyte viability, reducing Cd-induced synoviocyte detachment from the plate [36]. At day 5, the viability score of Cd-Zn treated cells was twice that of Cd-only treated cells, whether cytokines were present or not (Fig 4A, p<0.05).…”

Section: Resultsmentioning

confidence: 99%

Regulatory effects of zinc on cadmium-induced cytotoxicity in chronic inflammation

Bonaventura¹,

Lamboux²,

Albarède³

et al. 2017

PLoS ONE

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ObjectivesZinc (Zn) has major effects on immune system activation while Cadmium (Cd) has anti-inflammatory and anti-proliferative effects in several chronic inflammatory contexts. The aim of this work was to investigate by which mechanisms Zn could compete with Cd and eventually counteract its deleterious effects. Rheumatoid arthritis (RA) synoviocytes exposed to cytokines were used as a model of chronic inflammation; osteoarthritis (OA) synoviocytes were used as control.MethodsCell/medium fractionation constants were analyzed for different metals by inductively-coupled-plasma mass-spectrometry by comparison to the 70Zn spike. Interleukin-17 (IL-17) and tumor necrosis factor-alpha (TNF-α) were used to mimic inflammation. Gene expression of ZIP-8 importer, metallothioneins-1 (MT-1s) and the ratio between metalloprotease-3 and the tissue inhibitor of metalloproteinases (MMP-3)/TIMP-1) were evaluated after pre-exposure to cytokines and Cd, with or without the addition of exogenous Zn (0.9 ppm). Cell viability was measured by neutral red assay and IL-6 production by ELISA.ResultsSynoviocytes selectively absorbed and retained Cd in comparison to Zn. Metal import increased with IL-17/TNF-α exposure, through the enhanced ZIP-8 expression. Zn did not modify ZIP-8 expression, while Cd reduced it (p<0.05). Zn induced a reduction of Cd-induced MT-1s expression, in particular of MT-1X (3-fold), and subsequently the final intra-cellular content of Cd. By reducing Cd accumulation in cells, Zn reversed Cd anti-proliferative and anti-inflammatory effects but preserved the low MMP-3/TIMP-1 ratio induced by Cd, which was enhanced by inflammatory conditions.ConclusionZinc counteracts the deleterious effect of Cd by reducing its import and accumulation in the cell, without the reactivation of destructive pathways such as MMPs.

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“…The altered expressions of MMPs (including MMP-1, MMP-3 and MMP-13) were observed in tendon cells and articular cartilage treated with quinolone (Corps et al, 2002(Corps et al, , 2005Goto et al, 2008), which was consistent in menisci in present study. Except for side effects in degradation of ECM, pro-apoptotic effect was also found in tendons, articular cartilage, synovium and ligaments treated with quinolones (De Sarro and De Sarro, 2001;Deng et al, 2011;Kappel et al, 2002;Tan et al, 2012;Yuan et al, 2002). Apoptosis of tendon cells is involved in the pathogenesis of tendon destruction (Yuan et al, 2002), and the activation of caspase-3 may mediate apoptosis (Yuan et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic effects of the quinolone levofloxacin on rabbit meniscus cells

Wang

Tan

et al. 2013

J of Applied Toxicology

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Quinolones have been reported to induce adverse effects on articular cartilage, tendons and ligaments. However, the effects of quinolones on menisci have not been revealed. The present study was to test the effects of levofloxacin on meniscus cells in vitro. Rabbit meniscus cells were administrated with different concentrations of levofloxacin (0, 14, 28, 56, 112 and 224 µm) for 24 or 48 h, and cell viability and apoptosis were measured. The mRNA expression levels of matrix metalloproteinase (MMP)-1, MMP-3, MMP-13, tissue inhibitors of metalloproteinase (TIMP)-1, TIMP-3, Col1a1, Bcl-2, caspase-3 and inducible nitric oxide were analyzed by real-time polymerase chain reaction. Active caspase-3 was detected by immunocytochemical assay, while protein expression levels of MMP-3 and MMP-13 were measured by Western blotting assay. After treatment with levofloxacin for 48 h, cell viability was decreased from dose of 28 to 224 µm in a concentration-dependent manner. An increase of apoptotic cells was observed by flow cytometry. Active caspase-3 protein expression level was also increased. The mRNA level of Bcl-2 was decreased and levels of MMP-1, MMP-3 and MMP-13 in experimental groups were higher than those of controls. The protein levels of MMP-3 and MMP-13 were increased. Moreover, the mRNA levels of TIMP-3 and col1a1 were decreased. A dose-dependent increase of inducible nitric oxide mRNA expression level was also observed. Our results suggested the cytotoxic effects of levofloxacin on meniscus cells through induction of apoptosis and unbalanced MMPs/TIMPs expression. These side effects might result in meniscus extracellular matrix degradation and meniscal lesion. Thus, quinolones should be used cautiously on patients who perform athletic activities or undergo surgical meniscus repair.

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The effects of levofloxacin on rabbit fibroblast-like synoviocytes in vitro

Cited by 18 publications

References 31 publications

Toxic Effects of Levofloxacin on Rat Annulus Fibrosus Cells: An In-vitro Study

Toxic Effects of Levofloxacin on Rat Annulus Fibrosus Cells: An In-vitro Study

Regulatory effects of zinc on cadmium-induced cytotoxicity in chronic inflammation

Cytotoxic effects of the quinolone levofloxacin on rabbit meniscus cells

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