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PeerJ2021; 9; e12003; doi: 10.7717/peerj.12003

Ciprofloxacin reduces tenocyte viability and proteoglycan synthesis in short-term explant cultures of equine tendon.

Abstract: Fluoroquinolones are an effective, broad-spectrum antibiotic used to treat an array of bacterial infections. However, they are associated with an increased risk of tendinopathy and tendon rupture even after discontinuation of treatment. This condition is known as fluoroquinolone-associated tendinopathy, the underlying mechanisms of which are poorly understood. While many factors may be involved in the pathophysiology of tendinopathies in general, changes in tenocyte metabolism and viability, as well as alteration of proteoglycan metabolism are prominent findings in the scientific literature. This study investigated the effects of ciprofloxacin, a common fluoroquinolone, on cell viability, proteoglycan synthesis, and proteoglycan RNA expression in equine superficial digital flexor tendon explants after 96 h treatment with between 1-300 µg/mL ciprofloxacin, and again after 8 days discontinuation of treatment. Ciprofloxacin caused significant reductions in cell viability by between 25-33% at all dosages except 10 µg/mL, and viability decreased further after 8 days discontinuation of treatment. Proteoglycan synthesis significantly decreased by approximately 50% in explants treated with 100 µg/mL and 300 µg/mL, however this effect reversed after 8 days in the absence of treatment. No significant RNA expression changes were observed after the treatment period with the exception of versican which was down-regulated at the highest concentration of ciprofloxacin. After the recovery period, aggrecan, biglycan and versican genes were all significantly downregulated in explants initially treated with 1-100 µg/mL. Results from this study corroborate previously reported findings of reduced cell viability and proteoglycan synthesis in a whole tissue explant model and provide further insight into the mechanisms underlying fluoroquinolone-associated tendinopathy and rupture. This study further demonstrates that certain ciprofloxacin induced cellular changes are not rapidly reversed upon cessation of treatment which is a novel finding in the literature.
Publication Date: 2021-08-30 PubMed ID: 34540363PubMed Central: PMC8411937DOI: 10.7717/peerj.12003Google Scholar: Lookup
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  • Journal Article

Summary

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The research article discusses the effects of the antibiotic ciprofloxacin on equine tenocytes, specifically its impact on cell viability and proteoglycan synthesis. The study shows that ciprofloxacin significantly reduces cell viability and proteoglycan synthesis, and that these effects persist even after discontinuation of treatment.

Background

  • The study builds upon scientific literature that associates fluoroquinolone antibiotics with an increased risk of tendinopathy and tendon rupture.
  • Equine tendon cells, or tenocytes, are used as a model for studying the adverse effects of ciprofloxacin, a common fluoroquinolone.

Methodology

  • Researchers studied the effects of ciprofloxacin on equine superficial digital flexor tendon explants with a dosage ranging between 1-300 µg/mL.
  • The impact of the antibiotic on cell viability, proteoglycan synthesis, and proteoglycan RNA expression was studied immediately after the 96-hour treatment period and then again after 8 days of discontinuation of treatment.

Findings

  • Ciprofloxacin was found to cause significant reductions in cell viability across all dosages except at 10 µg/mL. The viability further declined after the discontinuation of treatment.
  • Explants treated with 100 µg/mL and 300 µg/mL of ciprofloxacin showed about a 50% drop in proteoglycan synthesis. This effect was, however, reversed after 8 days of non-treatment.
  • There were no significant changes in RNA expression after treatment, except for the down-regulation of versican at the highest concentration of ciprofloxacin.
  • After the recovery period, the aggrecan, biglycan, and versican genes showed significant downregulation in explants initially treated with 1-100 µg/mL ciprofloxacin.

Conclusion

  • The findings of the study affirm the previous conclusions on ciprofloxacin’s side effects on tendons, giving further insights into the mechanisms of fluoroquinolone-associated tendinopathy and rupture.
  • The study highlighted an important finding that certain cellular changes induced by ciprofloxacin did not reverse quickly after discontinuing the treatment.

Cite This Article

APA
James S, Schuijers J, Daffy J, Cook J, Samiric T. (2021). Ciprofloxacin reduces tenocyte viability and proteoglycan synthesis in short-term explant cultures of equine tendon. PeerJ, 9, e12003. https://doi.org/10.7717/peerj.12003

Publication

ISSN: 2167-8359
NlmUniqueID: 101603425
Country: United States
Language: English
Volume: 9
Pages: e12003
PII: e12003

Researcher Affiliations

James, Stuart
  • Department of Physiology, Anatomy, and Microbiology, La Trobe University, Melbourne, Victoria, Australia.
Schuijers, Johannes
  • Department of Physiology, Anatomy, and Microbiology, La Trobe University, Melbourne, Victoria, Australia.
Daffy, John
  • Department of Infectious Diseases, St. Vincent's Hospital, Melbourne, Victoria, Australia.
Cook, Jill
  • Sports and Exercise Medicine Research Centre, La Trobe University, Melbourne, Victoria, Australia.
Samiric, Tom
  • Department of Physiology, Anatomy, and Microbiology, La Trobe University, Melbourne, Victoria, Australia.

Conflict of Interest Statement

The authors declare that they have no competing interests.

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Citations

This article has been cited 2 times.
  1. James S, Daffy J, Cook J, Samiric T. Short-Term Exposure to Ciprofloxacin Reduces Proteoglycan Loss in Tendon Explants.. Genes (Basel) 2022 Nov 25;13(12).
    doi: 10.3390/genes13122210pubmed: 36553476google scholar: lookup
  2. Al-Neklawy AF, El-Nefiawy NE, Rady HY. Does oral ciprofloxacin affect the structure of thoracic aorta in adult and senile male albino rats? A clue to fluoroquinolones-induced risk of aortic dissection.. Anat Cell Biol 2022 Mar 31;55(1):79-91.
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