Effects of ciprofloxacin and ofloxacin on adult human cartilage in vitro (original) (raw)
Related papers
Antimicrobial agents and chemotherapy, 1999
Although fluoroquinolone antibacterials have a broad therapeutic use, with a relatively low incidence of severe side effects, they have been reported to induce lesions in the cartilage of growing animals by a mechanism that remains unclear. This study was undertaken to determine the potentially deleterious effect of a high dose of pefloxacin (400 mg/kg of body weight) on two main constituents of cartilage in mice, i.e., proteoglycans and collagen. Variations in levels of proteoglycan anabolism measured by in vivo [(35)S]sulfate incorporation into cartilage and oxidative modifications of collagen assessed by detection of carbonyl derivatives were monitored after administration of pefloxacin. Treatment of mice with 1 day of pefloxacin treatment significantly decreased the rate of biosynthesis of proteoglycan for the first 24 h. However, no difference was observed after 48 h. The decrease in proteoglycan synthesis was accompanied by a marked drop in serum sulfate concentration and a co...
Cytofluorometric analysis of chondrotoxicity of fluoroquinolone antimicrobial agents
Antimicrobial Agents and Chemotherapy, 1994
To better understand quinolone-related arthropathy, we conceived an experimental ex vivo model using cell cultures of articular chondrocytes issued from pretreated New Zealand White rabbits (NZW). Juvenile (4to 5-week-old) NZW were orally dosed with ofloxacin or pefloxacin (300 mg/kg of body weight for 1 day) or with pefloxacin (300 mg/kg for 7 days). Adult (5-month-old) NZW were treated with pefloxacin (300 mg/kg for 1 day). Chondrocytes were enzymatically recovered from cartilage and were analyzed by cytofluorometry using 2',7'-dichlorofluorescein diacetate (DCFH-DA) and dihydrorhodamine 123 (DHR), reflecting cellular respiratory-burst activity, and rhodamine 123 (Rh123) and 10-N-nonyl-acridine orange (NAO), specific for the mitochondrial activity and mass, respectively. A significant increase in the respiratory burst was detected by DCFH-DA and DHR in all treated groups of young animals, compared with untreated control groups. No significant increase of respiratory burst was noted in older treated rabbits. The 7-day treatment resulted in a decrease in mitochondrial uptake of Rh123 and an increase in NAO uptake. Fluoroquinolone arthrotoxicity seems to involve in its early phase the respiratory burst of immature articular chondrocytes.
PeerJ
Background Previous studies reported the effect of enrofloxacin (Enro) and marbofloxacin (Mar) on cell death and alteration of the key genes involved in catabolic and anabolic processes and demonstrated the beneficial effects of hyaluronan (HA) combined with fluoroquinolones (FQs) on primary canine chondrocytes. This study further determines the effects of these treatments on canine cartilage explants in both normal and interleukin-1 beta (IL-1β)-stimulated conditions. Methods We examined sulfate glycosaminoglycan (s-GAG) release, uronic acid (UA) content, and safranin-O staining, as well as the expression patterns of inflammatory, extracellular matrix (ECM) component and enzymes. Results Enro treatment alone effectively stimulated proteoglycan anabolism by increasing UA content and glycosaminoglycans (GAGs) in normal and pre-IL-1β-stimulated explant, whereas Mar showed opposite results. The combination of HA and FQs increased s-GAG release and UA content in normal explants in addit...
The Effect of Fluoroquinolone Antibiotics on Growing Cartilage in the Lamb Model
Journal of Pediatric Orthopaedics, 2009
Background-The fluoroquinolones are a relatively new class of antimicrobials with an appealing spectrum of activity. Their use in pediatric medicine is limited due to concern over possible growth inhibition, as published reports have documented articular cartilage damage in animal models following their administration. This data, extrapolated to include the epiphyseal cartilage, suggests these agents may reduce growth rates, but limited human data is at the least equivocal, if not strictly contradictory to such claims. Specific investigations into the effects of fluoroquinolones on epiphyseal plate cartilage and growth velocity have not been performed. Methods-Gatifloxacin and ciprofloxacin were used as representative agents of the fluoroquinolone class. Each drug was administered to experimental lambs over a fourteen day interval, at a dose designed to reflect those used in pediatric medicine. Recumbent versus standing intervals were used to monitor for arthropathy. Upon completion of fluoroquinolone administration, lambs underwent double fluorochrome labeling for determination of growth velocity. Gross and microscopic analysis of articular cartilage was performed to assess for pathologic changes. Age and gender matched lambs served as controls. Results-Neither gatifloxacin nor ciprofloxacin negatively affected growth velocity of the proximal tibial growth plate as measured by double fluorochrome labeling. Additionally, no difference between experimental and control lambs in regard to recumbent versus standing intervals was noted. Examination of the articular cartilage failed to suggest chondrotoxicity. Conclusion-Fluoroquinolone antimicrobials do not affect growth velocity in the ovine model when administered along a dosing regimen that closely models that seen in pediatric medicine. Clinical Relevance-Fluoroquinolones may be acceptable for use in the pediatric population, as concerns over chondrotoxicity and growth inhibition may not be valid. This data suggests that expanded studies in lambs and other species, including humans, with differences in dosing and duration are justified to ultimately demonstrate clinical safety.
In Vitro Effect of Vancomycin on the Viability of Articular Chondrocytes
Journal of orthopaedic trauma, 2017
To characterize the in-vitro toxicity of vancomycin on articular cartilage. Osteochondral samples extracted from fresh, juvenile porcine stifle (knee) joints were exposed to vancomycin-saline concentrations of 2, 5, and 10 mg/ml and compared to a saline and non-saline treated control. Comparison chondrocyte viability was assessed with histology examination of chondrocyte degeneration using the Mankin criteria and a live/dead staining using ethidium homodimer-2 and calcien acetoxymethylester (AM) stain and confocal laser scanning microscopy. A comparison of chondrocyte viability in the control sample and 2 mg/ml group showed no statistical difference (p = 0.38). The chondrocyte toxicity was statistically significantly higher in both the 5 mg/ml (p = 0.003) and 10 mg/ml (p < 0.001) experimental groups in comparison to the control sample. Chondrocyte death increased in a statistically significant dose dependent fashion. Histologically, Mankin scores were higher for the saline-treate...
Enrofloxacin effect on histomorphologic and histomorphometric structure of lamb articular cartilage
Enrofloxacin is a synthetic chemotherapeutic agent from the class of the fluoroquinolones that is widely used to treat bacterial infections in animals. Fluoroquinolones cause some lesions in articular cartilage of growing mammals so with due attention to clinical importance of enrofloxacin, comprehensive study for cellular and molecular damaging events in articular cartilage due to consumption of this drug has been designed and in this paper, histological part has been presented. Thus the aim of the present study was investigation of enrofloxacin effect on histomorphologic and histomorphometric structure of lamb articular cartilage. Twelve, 2-month-old male lambs were divided 3 groups; control group, therapeutic group: received 5mg/kg enrofloxacin subcutaneously for 15 days and toxic group received 35 mg/kg enrofloxacin subcutaneously for 15 days. Control group received distilled water subcutaneously. Twenty four hours after the last dose the animals were euthanaized and stifle joint was dissected. Distal femoral and proximal tibial extremities were grossly examined then routine histological sections were prepared and evaluated by light microscope. Macroscopic changes as erosion and flap were seen on distal femoral and proximal tibial articular cartilages only in toxic group. Histological changes included decrease of matrix proteoglycans, total cartilage thickness and chondrocyte numbers. Also presence of spindle-shaped cells, fissure in articular cartilarge matrix and increase of empty lacuna were observed in toxic group while chondrocyte numbers significantly decreased and empty lacuna increased in therapeutic group with comparison to control group. In conclusion, results of this study indicate that the use of enrofloxacin in growing lambs at recommended (therapeutic) dosage is not completely safe on articular cartilage. However higher doses of enrofloxacin induce sever changes in lamb articular cartilage.
Acta medica Iranica, 2015
Enrofloxacin is a synthetic chemotherapeutic agent from the class of the fluoroquinolones that is widely used to treat bacterial infections. It is metabolized to ciprofloxacin in the body as active metabolite. Fluoroquinolones change in the articular cartilage, especially with high doses and more than two weeks use. So, due to relatively excessive use of enrofloxacin in mammals and similarity of lambs to human subjects with respect to skeletal activity cycles, this study was done to investigate the effects of enrofloxacin on some cellular and molecular changes in growing lamb articular cartilage to evaluate some possible mechanisms involved these changes. Twelve, 2-month-old male lambs divided into three groups: control group received only normal saline; therapeutic group received 5mg/kg enrofloxacin subcutaneously, daily, for 15 days and toxic group received 35 mg/kg enrofloxacin in the same manner as therapeutic group. Twenty four hours after the last dose, the animals were sacrif...
Experimental and therapeutic medicine, 2018
Non-steroidal anti-inflammatory drugs (NSAIDs) that are applied through oral, injectable or topical routes have been widely used in painful and inflammatory musculoskeletal diseases. The current study aimed to determine whether naproxen, an aryl acetic acid derivative with analgesic and anti-inflammatory effects, has a toxic effect on human chondrocytes. Samples containing monolayer primary chondrocyte cultures were prepared following resection from osteochondral tissues obtained from patients with gonarthrosis. Cell viability, toxicity and proliferation and levels of stage-specific embryonic antigen-1, a precursor to human prechondrocytes, were evaluated spectrophotometrically. The results from the untreated control group were compared with those of the study groups, where naproxen was administered in varying doses (1-1,000 µM). Surface morphologies of the cells were compared using inverted light and environmental scanning electron microscopy. Treatment groups were compared by anal...