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In vitro study of cytotoxicity of quinolones on rabbit tenocytes

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Abstract

Tendinitis and tendon rupture complicating fluoroquinolone therapy have been reported recently, especially affecting men over 60 years. These new quinolones are more potent antimicrobial agents than older nonfluorinated compounds like nalidixic acid. We compared the effects of one quinolone (nalidixic acid) and two fluoroquinolones (norfloxacin and pefloxacin) on cultured rabbit Achilles tendon cells. First, we examined their effects on cell viability, mitochondrial succinate dehydrogenase and global activity, mitochondrial activity using microtitration methods. Pefloxacin and norfloxacin were more cytotoxic than nalidixic acid according to IC50 values. These results confirm that mitochondria represent a biological target of fluoroquinolones. Moreover, the extracellular matrix was studied by molecular hybridization. After a 72 h treatment, the level of type I collagen transcripts was not modified with any of the three antimicrobial agents, whereas mRNA encoding decorin was decreased with 10-4 mol/L pefloxacin only. The decrease of transcripts encoding decorin suggests that this matrix component is another target of pefloxacin and modification of decorin seems to be an early event (before mitochondrion alteration) which may contribute to the explanation of tendon rupture.

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References

  • Adams EG, Barden K, Badiner R, Ulrich R, Bhuyan, BK. Evaluation of rhodamine 123 as a fluorescent probe to assess mitochondrial damage due to cytotoxic drugs. Cell Tissue Kinet. 1984;17:670–8.

    Google Scholar 

  • Arnheim N. Characterization of mouse ribosomal gene fragments purified by molecular cloning. Gene. 1979;7:83–96.

    Google Scholar 

  • Barret JF, Gootz TD, McGuirk PR, Farrell CA, Sokolowski SA. Use of in vitro topoisomerase assays for studying quinolone antibacterial agents. Antimicrob Agents Chemother. 1989;33:1697–703.

    Google Scholar 

  • Bernard-Beaubois KB, Hecquet C, Houcine O, Hayem G, Adolphe M. Culture and characterization of juvenile rabbit tenocytes. Cell Biol Toxicol. 1997;13:103–13.

    Google Scholar 

  • Burkhardt JE, Hill MA, Carlton W. Morphologic and biochemical changes in articular cartilages of immature beagle dogs dosed with difloxacin. Toxicol Pathol. 1992;20:246–52.

    Google Scholar 

  • Castora FJ, Vissering FF, Simpson. The effect of bacterial DNA gyrase inhibitors on DNA synthesis in mammalian mitochondria. Biochim Biophys Acta. 1983;740:417–27.

    Google Scholar 

  • Chaslerie A, Bannwarth B, Landreau JM, Yver L, Bégaud B. Ruptures tendineuses et fluoroquinolones: un effet indésirable de classe. Rev Rhum Mal Osteoartic. 1992;59:297.

    Google Scholar 

  • Chen LB, Summerhayes IC, Johnson LV, Walsh ML, Bernal SD, Lampidis TI. Probing mitochondria in living cells with Rhodamine 123. Cold Spring Harbor Symp Quant Biol. 1981;46:141–55.

    Google Scholar 

  • Chomanzynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate phenol-chloroform extraction. Anal Biochem. 1987;162:156–9.

    Google Scholar 

  • Denizot F, Lang R. Rapid colorimetric assay for cell growth and survival. Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. J Immunol Methods. 1986;89:271–7.

    Google Scholar 

  • Donck JB, Segaert MF, Vanrenterghem YF. Fluoroquinolones and Achilles tendinopathy in renal transplant recipients. Transplantation. 1994;58:736–7.

    Google Scholar 

  • Gough A, Barsoum N, Renlund R, Sturgess J, De La Iglesia F. Fine structural changes during reparative phase of canine drug-induced arthropathy. Vet Pathol. 1985;22:82–4.

    Google Scholar 

  • Gough A, Johnson R, Campbell E et al. Quinolone arthropathy in immature rabbits treated with the fluoroquinolone, PD 117596. Exp Toxicol Pathol. 1996;48:225–32.

    Google Scholar 

  • Hayem G, Petit PX, Levacher M, Gaudin C, Kahn MF, Pocidalo JJ. Cytofluorometric analysis of chondrotoxicity of fluoroquinolone antimicrobial agents. Antimicrob Agents Chemother. 1994;38:243–7.

    Google Scholar 

  • Hildebrand H, Kempka G, Schluüter G, Schmidt M. Chondro-toxicity of quinolones in vivo and in vitro. Arch Toxicol. 1993;67:411–5.

    Google Scholar 

  • Hooper DC, Wolfson JS. The fluoroquinolones: pharmacology, clinical uses and toxicities in humans. Antimicrob Agents Chemother. 1985;28:716–21.

    Google Scholar 

  • Hooper DC, Wolfson JS. Mode of action of the quinolone antimicrobial agents: review of recent information. Rev Infect Dis. 1989;11(supplement 5):902–11.

    Google Scholar 

  • Iozzo RV, Cohen I. Altered proteoglycan gene expression and the tumor stroma. Experientia. 1993;49:447–55.

    Google Scholar 

  • Jorgensen C, Anaya JM, Didry C. Arthropathies et tendinopathies achillé ennes induites par la péfloxacine. A propos d'une observation. Rev Rhum Mal Osteoartic. 1991;58: 623–5.

    Google Scholar 

  • Kato M, Takada S, Kashida Y, Nomura M. Histological examination on Achilles tendon lesions induced by quinolone antibacterial agents in juvenile rats. Toxicol Pathol. 1995;23:385–92.

    Google Scholar 

  • Krusius T, Ruoslahti E. Primary structure of an extracellular matrix proteoglycan core protein deduced from cloned cDNA. Proc Natl Acad Sci USA. 1986;83:7683–7.

    Google Scholar 

  • Kull FC, Cuatrecasas P. Estimation of cell number by neutral red content: applications for proliferative and survival assays. Appl Biochem Biotechnol. 1983;8:97–103.

    Google Scholar 

  • Mäkelä JK, Raassina M, Virta A, Vuorio E. Human proal(I) collagen: cDNA sequence for the C-propeptide domain. Nucleic Acids Res. 1988;19:349.

    Google Scholar 

  • Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65:55–63.

    Google Scholar 

  • Rat P, Christen MO, Thevenin M. Cold light fluorometry: a new microtitration technology for cell culture. Application to the evaluation of anethole dithiolethione and other biothols. Methods Enzymol. 1995;252:331–40.

    Google Scholar 

  • Ribard P, Kahn MF. Rheumatological side-effects of quinolones. In: Kahn MF, ed. Bailliè re's clinical rheumatology; Drug-induced rheumatic diseases. London: Baillliè re Tin-Dall; 1991:175–91.

    Google Scholar 

  • Ribard P, Audisio F, Kahn MF et al. Seven Achilles tendinitis including three complicated by rupture during fluoroquinolone therapy. J Rheumatol. 1992;19:1479–81.

    Google Scholar 

  • Royer RJ, Pierfitte C, Netter P. Features of tendon disorders with fluoroquinolones. Therapie. 1994;49:75–6.

    Google Scholar 

  • Sharpnack DD, Mastin JP, Childress CP, Henningsen GM. Quinolone arthropathy in juvenile New Zealand White rabbits. Lab Anim Sci. 1994;44:436–42.

    Google Scholar 

  • Stahlmann R, Lode H. The quinolones — safety overview: toxicity, adverse effects and drug interactions. In: Andriole VT, ed. The quinolones. London: Academic Press; 1988: 201–33.

    Google Scholar 

  • Takayama S, Hirohashi M, Kato M, Shimada H. Toxicity of quinolone antibacterial agents. J Toxicol Environ Health. 1995;45:1–45.

    Google Scholar 

  • Vogel K, Keller J, Lenhoff R, Campbell K, Koob J. Proteoglycan synthesis by fibroblast cultures initiated from regions of adult bovine tendon subjected to different mechanical forces. Eur J Cell Biol. 1986;41:102–12.

    Google Scholar 

  • Zabraniecki L, Negrier I, Vergne P et al. Fluoroquinolone induced tendinopathy: report of 6 cases. J Rheumatol. 1996;23:516–20.

    Google Scholar 

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Bernard-Beaubois, K., Hecquet, C., Hayem, G. et al. In vitro study of cytotoxicity of quinolones on rabbit tenocytes. Cell Biol Toxicol 14, 283–292 (1998). https://doi.org/10.1023/A:1007435025616

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