Siengdee P, Euppayo T, Buddhachat K, Chomdej S, Nganvongpanit K
Animal Bone and Joint Research Laboratory, Department of Veterinary Biosciences and Public Health, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, Thailand.
Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai, Thailand.
J Vet Pharmacol Ther. 2016 Oct;39(5):439-51. doi: 10.1111/jvp.12305. Epub 2016 Mar 11.
Fluoroquinolones (FQs) are frequently used for septic arthritis. Increased antibacterial activity has been associated with mammalian cell cytotoxicity that may increase the risk of developing osteoarthritis. This study compared the direct effects of two different FQs, enrofloxacin (Enro) and marbofloxacin (Mar), on normal primary canine chondrocytes and inflammatory-stimulated chondrocytes, in addition to their administration in combination with hyaluronan (HA). Cell viability, cell apoptosis, s-GAG production, and expression patterns of inflammatory, extracellular matrix (ECM) component and protease genes were measured. Enro co-culturing with HA could modify s-GAG synthesis compared with the negative control group. Co-treatment with both FQs and HA significantly decreased cell viability and induced more total apoptotic cell death compared with the negative control and pre-IL-1β-stimulated group. Enro regulated IL-1β-stimulated cells to overexpress IL-1β, TNF, and MMP3, whereas Mar induced upregulation of PTGS2 and NFKB1 and enhanced the expression of ECM component genes HAS1, COL2A1, and ACAN as well as TIMP1 and MMP9. Simultaneous use of HA with Enro can effectively reduce the expression of IL-1β, TNF, and MMP3 in pre-IL-1β-stimulated chondrocytes. These results suggest the beneficial effects of HA in reducing the adverse effects of Enro treatment at the transcriptional level.
氟喹诺酮类药物（FQs）常用于治疗化脓性关节炎。其抗菌活性增强与哺乳动物细胞毒性有关，这可能会增加患骨关节炎的风险。本研究比较了两种不同的氟喹诺酮类药物恩诺沙星（Enro）和马波沙星（Mar）对正常原代犬软骨细胞和炎症刺激软骨细胞的直接影响，以及它们与透明质酸（HA）联合使用的效果。检测了细胞活力、细胞凋亡、硫酸糖胺聚糖（s-GAG）产生以及炎症、细胞外基质（ECM）成分和蛋白酶基因的表达模式。与阴性对照组相比，Enro与HA共培养可改变s-GAG的合成。与阴性对照组和白细胞介素-1β（IL-1β）刺激前的组相比，FQs与HA联合处理显著降低了细胞活力，并诱导了更多的总凋亡细胞死亡。Enro调节IL-1β刺激的细胞过度表达IL-1β、肿瘤坏死因子（TNF）和基质金属蛋白酶3（MMP3），而Mar诱导前列腺素内过氧化物合酶2（PTGS2）和核因子κB亚基1（NFKB1）上调，并增强了ECM成分基因透明质酸合酶1（HAS1）、Ⅱ型胶原α1链（COL2A1）和聚集蛋白聚糖（ACAN）以及金属蛋白酶组织抑制因子1（TIMP1）和MMP9的表达。HA与Enro同时使用可有效降低IL-1β刺激前软骨细胞中IL-1β、TNF和MMP3的表达。这些结果表明，HA在转录水平上对减轻Enro治疗的不良反应具有有益作用。
