Background: Levofloxacin (LVFX) is widely used for many respiratory, urinary, and oral infections. Although rare, tendinopathy and tendon rupture have been reported in patients treated with LVFX as adverse effect. However, the exact mechanism is not fully elucidated. In this study, we investigated the effects of LVFX on tendon cells and tendon tissue. Method: Murine tendon cell line TT-D6 cells were treated with LVFX. Total RNA was extracted from the treated cells and quantitative reverse-transcription polymerase chain reaction (RT-PCR). LVFX-treated TT-D6 cells were subjected to cell proliferation assays and reactive oxygen species production assays. In addition, LVFX was administered to rats, and total RNA was extracted from tendon tissue and quantitatively analyzed for mRNA expression using quantitative RT-PCR. Results: Proliferative capacity in TT-D6 cells treated with various concentrations of LVFX showed no significant differences in any of the group comparisons. Quantitative RT-PCR analysis in TT-D6 cells showed that collagen 12a1 (COL12A1) expression was significantly decreased in the LVFX-treated group compared with the control group. The expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 was significantly increased in the LVFX group. On the other hand, there were no significant differences in mRNA expression of decorin, matrix metalloproteinase-9, and Collagen1a1. ROS production was significantly upregulated in LVFX-treated rats, and COL12A1 expression was significantly decreased in LVFX-treated rats compared with controls in tendons collected from LVFX-treated rat models. Conclusions: Taken together, COL12A1 reduction may be involved in tendon injury and tendon rupture in LVFX administration, suggesting that increased ROS production may be involved.
Published in | Science Journal of Clinical Medicine (Volume 13, Issue 4) |
DOI | 10.11648/j.sjcm.20241304.11 |
Page(s) | 63-70 |
Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
Copyright |
Copyright © The Author(s), 2024. Published by Science Publishing Group |
Levofloxacin, Adverse Effect, Tendon, Type XII Collagen, Reactive Oxygen Species
[1] | Baik S, Lau J, Huser V, McDonald CJ. Association between tendon ruptures and use of fluoroquinolone, and other oral antibiotics: a 10-year retrospective study of 1 million US senior Medicare beneficiaries. BMJ Open 2020; 10: e034844. |
[2] | Asoda S, Iwasaki R, Fukaya C, Hosaka Y, Usuda S, Kawana H, et al. Oral and maxillofacial tissue penetration of levofloxacin following oral administration of a single 500 mg dose. Jpn J Chemother 2012; 60: 643-5. |
[3] | Shu Y, Zhang Q, He X, Liu Y, Wu P, Chen L. Fluoroquinolone-associated suspected tendonitis and tendon rupture: A pharmacovigilance analysis from 2016 to 2021 based on the FAERS database. Front Pharmacol 2022; 13: 990241. |
[4] | Riley G. Tendinopathy-from basic science to treatment. Nat Clin Pract Rheumatol 2008; 4: 82-9. |
[5] | Gordon MK, Gerecke DR, Olsen BR. Type XII collagen: distinct extracellular matrix component discovered by cDNA cloning. Proc Natl Acad Sci U S A 1987; 84: 6040-4. |
[6] | Böhme K, Li Y, Oh PS, Olsen BR. Primary structure of the long and short splice variants of mouse collagen XII and their tissue-specific expression during embryonic development. Dev Dyn 1995; 204: 432-45. |
[7] | Karimbux NY, Nishimura I. Temporal and spatial expressions of type XII collagen in the remodeling periodontal ligament during experimental tooth movement. J Dent Res 1995; 74: 313-8. |
[8] | Chiquet M, Birk DE, Bönnemann CG, Koch M. Collagen XII: Protecting bone nd muscle integrity by organizing collagen fibrils. Int J Biochem Cell Biol 2014; 53: 51-4. |
[9] | Izu Y, Birk DE. Collagen XII mediated cellular and extracellular mechanisms in development, regeneration, and disease. Front Cell Dev Biol 2023; 11: 1129000. |
[10] | Corrao G, Zambon A, Bertù L, Mauri A, Paleari V, Rossi C, et al. Evidence of tendinitis provoked by fluoroquinolone treatment: a case-control study. Drug Saf 2006; 29: 889-96. |
[11] | Lewis T, Cook J. Fluoroquinolones and tendinopathy: a guide for athletes and sports clinicians and a systematic review of the literature. J Athl Train 2014; 49: 422-7. |
[12] | Gold L, Igra H. Levofloxacin-induced tendon rupture: a case report and review of the literature. J Am Board Fam Pract 2003; 16: 458-60. |
[13] | Kowatari K, Nakashima K, Ono A, Yoshihara M, Amano M, Toh S. Levofloxacin-induced bilateral Achilles tendon rupture: a case report and review of the literature. J Orthop Sci 2004; 9: 186-90. |
[14] | Bestwick CS, Maffulli N. Reactive oxygen species and tendinopathy: do they matter? Br J Sports Med 2000; 8: 6-16. |
[15] | Longo UG, Oliva F, Denaro V, Maffulli N. Oxygen species and overuse tendinopathy in athletes. Disabil Rehabil 2008; 30: 1563-71. |
[16] | Pouzaud F, Bernard-Beaubois K, Thevenin M, Warnet JM, Hayem G, Rat P. In vitro discrimination of fluoroquinolones toxicity on tendon cells: involvement of oxidative stress. J Pharmacol Exp Ther 2004; 308: 394-402. |
[17] | Kaleagasioglu F, Olcay E. Fluoroquinolone-induced tendinopathy: etiology and preventive measures. Tohoku J Exp Med 2012; 226: 251-8. |
[18] | Salingcarnboriboon R, Yoshitake H, Tsuji K, Obinata M, Amagasa T, Nifuji A, et al. Establishment of tendon-derived cell lines exhibiting pluripotent mesenchymal stem cell-like property. Exp Cell Res 2003; 287: 289-300. |
[19] | Shakibaei M, Förster C, Merkel HJ. et al. Ofloxacin Alters Expression of Integrins on Chondrocytes from Mouse Fetuses In Vitro. Drugs 1995; 49: 293–5. |
[20] | Bidell MR, Lodise TP. Fluoroquinolone-Associated Tendinopathy: Does Levofloxacin Pose the Greatest Risk? Pharmacotherapy 2016; 36: 679-93. |
[21] | Tsai WC, Hsu CC, Chen CP, Chang HN, Wong AM, Lin MS. Ciprofloxacin up-regulates tendon cells to express matrix metalloproteinase-2 with degradation of type I collagen. J Orthop Res 2011; 29: 67-73. |
[22] | Nishiyama T, McDonough AM, Bruns RR, Burgeson RE. Type XII and XIV collagens mediate interactions between banded collagen fibers in vitro and may modulate extracellular matrix deformability. J Biol Chem 1994; 269: 28193-9. |
[23] | Izu Y, Adams SM, Connizzo BK, Beason DP, Soslowsky LJ, Koch M, et al. Collagen XII mediated cellular and extracellular mechanisms regulate establishment of tendon structure and function. Matrix Biol 2021; 95: 52-67. |
[24] | Fukusato S, Nagao M, Fujihara K, Yoneda T, Arai K, Koch M, et al. Collagen XII Deficiency Increases the Risk of Anterior Cruciate Ligament Injury in Mice. J Clin Med 2021; 10: 4051. |
[25] | Karousou E, Ronga M, Vigetti D, Passi A, Maffulli N. Collagens, proteoglycans, MMP-2, MMP-9 and TIMPs in human achilles tendon rupture. Clin Orthop Relat Res 2008; 466: 1577-82. |
APA Style
Kobayashi, T., Sato, T., Isozaki, Y., Okubo, M., Asoda, S., et al. (2024). Decreased Collagen Xii Expression and Increased Reactive Oxygen Species Production in Levofloxacin-Treated Tendon. Science Journal of Clinical Medicine, 13(4), 63-70. https://doi.org/10.11648/j.sjcm.20241304.11
ACS Style
Kobayashi, T.; Sato, T.; Isozaki, Y.; Okubo, M.; Asoda, S., et al. Decreased Collagen Xii Expression and Increased Reactive Oxygen Species Production in Levofloxacin-Treated Tendon. Sci. J. Clin. Med. 2024, 13(4), 63-70. doi: 10.11648/j.sjcm.20241304.11
AMA Style
Kobayashi T, Sato T, Isozaki Y, Okubo M, Asoda S, et al. Decreased Collagen Xii Expression and Increased Reactive Oxygen Species Production in Levofloxacin-Treated Tendon. Sci J Clin Med. 2024;13(4):63-70. doi: 10.11648/j.sjcm.20241304.11
@article{10.11648/j.sjcm.20241304.11, author = {Takashi Kobayashi and Tsuyoshi Sato and Yuta Isozaki and Masahiko Okubo and Seiji Asoda and Toshinori Iwai and Shinnosuke Nogami and Ko Ito}, title = {Decreased Collagen Xii Expression and Increased Reactive Oxygen Species Production in Levofloxacin-Treated Tendon }, journal = {Science Journal of Clinical Medicine}, volume = {13}, number = {4}, pages = {63-70}, doi = {10.11648/j.sjcm.20241304.11}, url = {https://doi.org/10.11648/j.sjcm.20241304.11}, eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.sjcm.20241304.11}, abstract = {Background: Levofloxacin (LVFX) is widely used for many respiratory, urinary, and oral infections. Although rare, tendinopathy and tendon rupture have been reported in patients treated with LVFX as adverse effect. However, the exact mechanism is not fully elucidated. In this study, we investigated the effects of LVFX on tendon cells and tendon tissue. Method: Murine tendon cell line TT-D6 cells were treated with LVFX. Total RNA was extracted from the treated cells and quantitative reverse-transcription polymerase chain reaction (RT-PCR). LVFX-treated TT-D6 cells were subjected to cell proliferation assays and reactive oxygen species production assays. In addition, LVFX was administered to rats, and total RNA was extracted from tendon tissue and quantitatively analyzed for mRNA expression using quantitative RT-PCR. Results: Proliferative capacity in TT-D6 cells treated with various concentrations of LVFX showed no significant differences in any of the group comparisons. Quantitative RT-PCR analysis in TT-D6 cells showed that collagen 12a1 (COL12A1) expression was significantly decreased in the LVFX-treated group compared with the control group. The expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 was significantly increased in the LVFX group. On the other hand, there were no significant differences in mRNA expression of decorin, matrix metalloproteinase-9, and Collagen1a1. ROS production was significantly upregulated in LVFX-treated rats, and COL12A1 expression was significantly decreased in LVFX-treated rats compared with controls in tendons collected from LVFX-treated rat models. Conclusions: Taken together, COL12A1 reduction may be involved in tendon injury and tendon rupture in LVFX administration, suggesting that increased ROS production may be involved. }, year = {2024} }
TY - JOUR T1 - Decreased Collagen Xii Expression and Increased Reactive Oxygen Species Production in Levofloxacin-Treated Tendon AU - Takashi Kobayashi AU - Tsuyoshi Sato AU - Yuta Isozaki AU - Masahiko Okubo AU - Seiji Asoda AU - Toshinori Iwai AU - Shinnosuke Nogami AU - Ko Ito Y1 - 2024/11/29 PY - 2024 N1 - https://doi.org/10.11648/j.sjcm.20241304.11 DO - 10.11648/j.sjcm.20241304.11 T2 - Science Journal of Clinical Medicine JF - Science Journal of Clinical Medicine JO - Science Journal of Clinical Medicine SP - 63 EP - 70 PB - Science Publishing Group SN - 2327-2732 UR - https://doi.org/10.11648/j.sjcm.20241304.11 AB - Background: Levofloxacin (LVFX) is widely used for many respiratory, urinary, and oral infections. Although rare, tendinopathy and tendon rupture have been reported in patients treated with LVFX as adverse effect. However, the exact mechanism is not fully elucidated. In this study, we investigated the effects of LVFX on tendon cells and tendon tissue. Method: Murine tendon cell line TT-D6 cells were treated with LVFX. Total RNA was extracted from the treated cells and quantitative reverse-transcription polymerase chain reaction (RT-PCR). LVFX-treated TT-D6 cells were subjected to cell proliferation assays and reactive oxygen species production assays. In addition, LVFX was administered to rats, and total RNA was extracted from tendon tissue and quantitatively analyzed for mRNA expression using quantitative RT-PCR. Results: Proliferative capacity in TT-D6 cells treated with various concentrations of LVFX showed no significant differences in any of the group comparisons. Quantitative RT-PCR analysis in TT-D6 cells showed that collagen 12a1 (COL12A1) expression was significantly decreased in the LVFX-treated group compared with the control group. The expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 was significantly increased in the LVFX group. On the other hand, there were no significant differences in mRNA expression of decorin, matrix metalloproteinase-9, and Collagen1a1. ROS production was significantly upregulated in LVFX-treated rats, and COL12A1 expression was significantly decreased in LVFX-treated rats compared with controls in tendons collected from LVFX-treated rat models. Conclusions: Taken together, COL12A1 reduction may be involved in tendon injury and tendon rupture in LVFX administration, suggesting that increased ROS production may be involved. VL - 13 IS - 4 ER -