The effects of levofloxacin on rabbit anterior cruciate ligament cells in vitro

被引:16
作者
Deng, Yu [1 ]
Chen, Biao [1 ]
Qi, Yongjian [1 ]
Magdalou, Jacques [3 ]
Wang, Hui [2 ]
Chen, Liaobin [1 ]
机构
[1] Wuhan Univ, Zhongnan Hosp, Dept Orthopaed Surg, Wuhan 430071, Peoples R China
[2] Wuhan Univ, Basic Med Sch, Dept Pharmacol, Wuhan 430071, Peoples R China
[3] Nancy Univ, Fac Med, CNRS, UMR 7561, Vandoeuvre Les Nancy, France
关键词
Levofloxacin; Anterior cruciate ligament; Cytotoxicity; Matrix metalloproteinases; Caspase-3; ACHILLES-TENDON; MATRIX METALLOPROTEINASES; CIPROFLOXACIN; EXPRESSION; FLUOROQUINOLONES; QUINOLONES;
D O I
10.1016/j.taap.2011.08.019
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Articular cartilage, epiphyseal growth plate and tendons have been recognized as targets of fluoroquinolone-induced connective tissue toxicity. The effects of fluoroquinolones on ligament tissues are still unknown. The aim of this study was to investigate the effects of levofloxacin, a typical fluoroquinolone antibiotic drug, on rabbit anterior cruciate ligament (ACL) cells in vitro. Rabbit ACL cells were treated with levofloxacin at different concentrations (0, 14, 28, 56, 112 and 224 mu M) and were assessed to determine the possible cytotoxic effects of levofloxacin on ACL cells. Levofloxacin, with concentrations ranging from 28 to 224 mu M, induced dose-dependent ACL cell apoptosis. Characteristic markers of programmed cell death and degenerative changes were identified by electron microscopy in the ACL cells treated with 28 mu M of levofloxacin. Moreover, levofloxacin significantly increased the mRNA expression of matrix metalloproteinase 3 (MMP-3) and MMP-13 and decreased the expression of tissue inhibitors of metalloproteinase 1 (TIMP-1) in a concentration-dependent manner; TIMP-3 and collagen type I alpha 1 (Col1A1) mRNA expression was not affected. Immunocytochemical analysis indicated that levofloxacin markedly increased the expression of active caspase-3 within a concentration range of 28 to 224 mu M, whereas a clear-cut decrease in Col1A1 expression was found with levofloxacin treatment concentrations of 112 and 224 mu M, compared to controls. Our data suggest that levofloxacin has cytotoxic effects on ACL cells characterized by enhanced apoptosis and decreased extracellular matrix, which suggest a potential adverse effect of fluoroquinolones. (C) 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码:67 / 73
页数:7
相关论文
共 32 条
  • [11] Tissue inhibitors of metalloproteinases (TIMP) in invasion and proliferation
    Henriet, P
    Blavier, L
    DeClerck, YA
    [J]. APMIS, 1999, 107 (01) : 111 - 119
  • [12] Tendon and ligament engineering in the adult organism: mesenchymal stem cells and gene-therapeutic approaches
    Hoffmann, Andrea
    Gross, Gerhard
    [J]. INTERNATIONAL ORTHOPAEDICS, 2007, 31 (06) : 791 - 797
  • [13] Effects of the des-F(6)-quinolone garenoxacin (BMS-284756), in comparison to those of ciprofloxacin and ofloxacin, on joint cartilage in immature rats
    Kappel, EM
    Shakibaei, M
    Bello, A
    Stahlmann, R
    [J]. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2002, 46 (10) : 3320 - 3322
  • [14] HISTOLOGICAL EXAMINATION ON ACHILLES-TENDON LESIONS INDUCED BY QUINOLONE ANTIBACTERIAL AGENTS IN JUVENILE RATS
    KATO, M
    TAKADA, S
    KASHIDA, Y
    NOMURA, M
    [J]. TOXICOLOGIC PATHOLOGY, 1995, 23 (03) : 385 - 392
  • [15] Levofloxacin-induced bilateral Achilles tendon rupture: a case report and review of the literature
    Kowatari, K
    Nakashima, K
    Ono, A
    Yoshihara, M
    Amano, M
    Toh, S
    [J]. JOURNAL OF ORTHOPAEDIC SCIENCE, 2004, 9 (02) : 186 - 190
  • [16] Messenger ribonucleic acid levels in disrupted human anterior cruciate ligaments
    Lo, IKY
    Marchuk, L
    Hart, DA
    Frank, CB
    [J]. CLINICAL ORTHOPAEDICS AND RELATED RESEARCH, 2003, (407) : 249 - 258
  • [17] Chitosan-based hyaluronan hybrid polymer fibre scaffold for ligament and tendon tissue engineering
    Majima, T.
    Irie, T.
    Sawaguchi, N.
    Funakoshi, T.
    Iwasaki, N.
    Harada, K.
    Minami, A.
    Nishimura, S-I
    [J]. PROCEEDINGS OF THE INSTITUTION OF MECHANICAL ENGINEERS PART H-JOURNAL OF ENGINEERING IN MEDICINE, 2007, 221 (H5) : 537 - 546
  • [18] Levofloxacin-associated Achilles tendon rupture
    Mathis, AS
    Chan, V
    Gryszkiewicz, M
    Adamson, RT
    Friedman, GS
    [J]. ANNALS OF PHARMACOTHERAPY, 2003, 37 (7-8) : 1014 - 1017
  • [19] Pathology of the Achilles tendon in association with ciprofloxacin treatment
    Movin, T
    Gad, A
    Guntner, P
    Foldhazy, Z
    Rolf, C
    [J]. FOOT & ANKLE INTERNATIONAL, 1997, 18 (05) : 297 - 299
  • [20] Oliphant CM, 2002, AM FAM PHYSICIAN, V65, P455