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The effects of enrofloxacin on decorin and glycosaminoglycans in avian tendon cell cultures

  • Organ Toxicity and Mechanisms
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Abstract

Tendonitis and tendon rupture have been reported to occur during or following therapy with fluoroquinolone antibiotics. Though the pathogenesis is unknown, several studies suggest that fluoroquinolone antibiotics alter proteoglycan content in soft tissues, including tendons, and thereby alter collagen fibrillogenesis. To better understand the mechanism of action of fluoroquinolones, we studied the effects of enrofloxacin, a widely used fluoroquinolone in veterinary medicine, on avian tendon cell cultures established from gastrocnemius tendons from 18-day-old chicken embryos. We found that cell proliferation was progressively inhibited with increasing concentrations of enrofloxacin. This was accompanied by changes in morphology, extracellular matrix content and collagen fibril formation as detected by electron microscopy. We also observed a 35% decrease in the content of total monosaccharides in enrofloxacin-treated cells. The ratio of individual monosaccharides was also altered in enrofloxacin-treated cells. Enrofloxacin also induced the synthesis of small amounts of keratan sulfate in tendon cells. Moreover we observed enrofloxacin-induced changes in glycosylation of decorin, the most abundant tendon proteoglycan, resulting in the emergence of multiple lower molecular bands that were identifiable as decorin after chondroitinase ABC and N-glycanase treatment of extracts from enrofloxacin-treated cells. Medium conditioned by enrofloxacin-treated cells contained less decorin than did medium conditioned by control cells. We hypothesize that enrofloxacin induces either changes in the number of N-linked oligosaccharides attached to the core protein of decorin or changes in decorin degradation process. In conclusion, our data suggest that enrofloxacin affects cell proliferation and extracellular matrix through changes in glycosylation.

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Acknowledgements

This study was supported by a grant from The University of Georgia Research Foundation. We thank Dr. W.L. Steffens and Ms. Mary Ard for performing electron microscopy, and Dr. S.C. Budsberg for helpful discussions. Special thanks have to go to Ms. Trina Abbeny for help with GC-MS analysis and to Dr. L.S. Leshin for help with statistical analysis. The experiments comply with the current US laws.

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Author notes

  1. Jung Hae Yoon

    Present address: Department of Biochemistry, Blacksburg, VA 24061, USA

  2. Randolph L. Brooks Jr.

    Present address: Dept. of Medicine/Rheumatology, University of California at San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA

  3. David Isaacs

    Present address: University of Health Sciences College of Osteopathic Medicine, 1750 Independence Avenue, Kansas City, MO 64106, USA

Authors and Affiliations

  1. The Soft Tissue Center, Department of Pathology, College of Veterinary Medicine, The University of Georgia, Athens, GA 30602, USA

    Jung Hae Yoon, Randolph L. Brooks Jr., Jian Zeng Zhao, David Isaacs & Jaroslava Halper

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  1. Jung Hae Yoon
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Correspondence to Jaroslava Halper.

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Yoon, J.H., Brooks, R.L., Zhao, J.Z. et al. The effects of enrofloxacin on decorin and glycosaminoglycans in avian tendon cell cultures. Arch Toxicol 78, 599–608 (2004). https://doi.org/10.1007/s00204-004-0574-z

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