PMID- 21903125 OWN - NLM STAT- MEDLINE DCOM- 20120113 LR - 20141120 IS - 1096-0333 (Electronic) IS - 0041-008X (Linking) VI - 257 IP - 1 DP - 2011 Nov 15 TI - The effects of levofloxacin on rabbit anterior cruciate ligament cells in vitro. PG - 67-73 LID - 10.1016/j.taap.2011.08.019 [doi] AB - 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 muM) and were assessed to determine the possible cytotoxic effects of levofloxacin on ACL cells. Levofloxacin, with concentrations ranging from 28 to 224 muM, 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 muM 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 muM, whereas a clear-cut decrease in Col1A1 expression was found with levofloxacin treatment concentrations of 112 and 224 muM, 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. CI - Copyright (c) 2011 Elsevier Inc. All rights reserved. FAU - Deng, Yu AU - Deng Y AD - Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, China. FAU - Chen, Biao AU - Chen B FAU - Qi, Yongjian AU - Qi Y FAU - Magdalou, Jacques AU - Magdalou J FAU - Wang, Hui AU - Wang H FAU - Chen, Liaobin AU - Chen L LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110827 PL - United States TA - Toxicol Appl Pharmacol JT - Toxicology and applied pharmacology JID - 0416575 RN - 0 (Anti-Bacterial Agents) RN - 6GNT3Y5LMF (Levofloxacin) RN - A4P49JAZ9H (Ofloxacin) SB - IM MH - Animals MH - Anterior Cruciate Ligament/cytology/*drug effects/ultrastructure MH - Anti-Bacterial Agents/*pharmacology MH - Cells, Cultured MH - Dose-Response Relationship, Drug MH - In Vitro Techniques MH - *Levofloxacin MH - Microscopy, Electron, Transmission MH - Ofloxacin/*pharmacology MH - Rabbits MH - Reverse Transcriptase Polymerase Chain Reaction EDAT- 2011/09/10 06:00 MHDA- 2012/01/14 06:00 CRDT- 2011/09/10 06:00 PHST- 2011/07/17 00:00 [received] PHST- 2011/08/15 00:00 [revised] PHST- 2011/08/19 00:00 [accepted] PHST- 2011/09/10 06:00 [entrez] PHST- 2011/09/10 06:00 [pubmed] PHST- 2012/01/14 06:00 [medline] AID - S0041-008X(11)00333-4 [pii] AID - 10.1016/j.taap.2011.08.019 [doi] PST - ppublish SO - Toxicol Appl Pharmacol. 2011 Nov 15;257(1):67-73. doi: 10.1016/j.taap.2011.08.019. Epub 2011 Aug 27.