The effects of levofloxacin on rabbit fibroblast-like synoviocytes in vitro.
It is widely accepted that tendon and cartilage are adversely affected with the toxic effects of quinolones. However, the effects of quinolones on synovium have not been deciphered completely. In this study, our main objective was to investigate the effects of levofloxacin, a typical quinolone antibiotic drug, on fibroblast-like synoviocytes (FLSs) in vitro. FLSs of rabbits were treated with levofloxacin at different concentrations (0, 14, 28, 56, 112 and 224 μM). The possible cytotoxic effects of levofloxacin on FLS were determined. Levofloxacin significantly reduced the cell viabilities, gene expression of hyaluronan synthase-2 (HAS-2), and the level of hyaluronan in FLSs. Moreover, levofloxacin-induced concentration-dependent increases of apoptosis and active caspase-3 were determined in this study. Ultrastructural damages of FLSs were observed by electron microscopy. The mRNA expression levels of matrix metalloproteinase (MMP)-3 and MMP-13 were increased in FLSs treated with levofloxacin. In addition, levofloxacin played a role in suppressing the expression of interleukin (IL)-1 and IL-6. Our data suggest that the cytotoxic effects of levofloxacin on FLS were shown to be able to affect cell viability and HA synthesis capacity. The potential mechanisms of the cytotoxic effects may be attributed to the apoptosis and increased expression of MMPs.
Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.
Yang
Y
Tan
Kaihang
K
Lu
Yu
Y
Deng
Hong
H
Cao
Biao
B
Chen
Hui
H
Wang
Jacques
J
Magdalou
Liaobin
L
Chen
D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D017209:Apoptosis / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism*; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000378:metabolism*; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D064704:Levofloxacin; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D015242:Ofloxacin / Q000633:toxicity*; D012313:RNA / Q000737:chemistry / Q000235:genetics; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013583:Synovial Membrane / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism
D000900:Anti-Bacterial Agents; D007375:Interleukin-1; D015850:Interleukin-6; D012313:RNA; D064704:Levofloxacin; D006820:Hyaluronic Acid; D015242:Ofloxacin; D014453:Glucuronosyltransferase; D000076002:Hyaluronan Synthases; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3