大豆/氨基葡萄糖/软骨素联合治疗对马软骨细胞抗生素毒性的影响

VCOT Open Pub Date : 2019-07-01 DOI:10.1055/s-0039-1693441
Cathleen A. Mochal-King, A. Rashmir, Lowella V. Fortuno, M. Grzanna, A. Au, J. Dougherty, C. Frondoza
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摘要

摘要目的本研究的目的是评估阿米卡星(AK)和恩诺沙星(EF)在与关节内和静脉局部肢体灌注浓度一致的情况下对马软骨细胞的细胞毒性和前列腺素E2 (PGE2)产生的影响。本研究还确定了鳄梨/大豆不皂化物(ASU)、氨基葡萄糖(GLU)和硫酸软骨素(CS)是否会降低PGE2的产量。研究设计从12匹马的关节软骨中培养单层软骨细胞,并给予临床相关浓度的AK和EF,有或没有ASU + GLU + CS联合治疗。阳性对照由脂多糖(LPS)激活的软骨细胞组成。采用MTT细胞毒性试验和免疫试验对PGE2的产生进行软骨细胞反应评估。结果阿米卡星和EF均呈剂量依赖性细胞毒性。阿米卡星在25 mg/mL浓度下诱导90%的细胞死亡。恩诺沙星1.0 mg/mL诱导90%细胞死亡,10 mg/mL诱导98%细胞死亡(p < 0.05)。阿米卡星在任何浓度下都不能诱导PGE2的产生。相反,EF和阳性对照(LPS)在所有浓度下都能诱导PGE2的产生。经ASU + GLU + CS预处理后,EF对PGE2的诱导均显著降低(p < 0.05)。结论和临床意义马接受常用剂量的AK和EF可能受益于给药ASU + GLU + CS。
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Mitigation of Antibiotic-Inducted Toxicity in Equine Chondrocytes by Soybean/Glucosamine/Chondroitin Combination
Abstract Objectives The aim of this study was to evaluate the effect of amikacin (AK) and enrofloxacin (EF) at concentrations consistent with those obtained by intra-articular and intravenous regional limb perfusion on both cytotoxicity and prostaglandin E2 (PGE2) production by equine chondrocytes. This study also determines if PGE2 production could be reduced by avocado/soybean unsaponifiables (ASU), glucosamine (GLU) and chondroitin sulphate (CS). Study Design Chondrocytes were grown in monolayer from the articular cartilage of 12 horses and treated with clinically relevant concentrations of AK and EF, with or without the combination of ASU + GLU + CS. Positive controls consisted of chondrocytes that were activated with lipopolysaccharide (LPS). Chondrocyte response was evaluated using both MTT cytotoxicity assay and immunoassay for PGE2 production. Results Amikacin and EF generated a dose-dependent cytotoxicity. Amikacin induced 90% cell death at a concentration of 25 mg/mL. Enrofloxacin induced 90% cell death at 1.0 mg/mL and 98% cell death at 10 mg/mL (p < 0.05). Amikacin failed to induce PGE2 production at any of the concentrations studied. In contrast, EF and the positive control (LPS) induced PGE2 production at all concentrations. Induction of PGE2 by EF at all concentrations was significantly reduced (p < 0.05) by pre-treatment with ASU + GLU + CS. Conclusions and Clinical Relevance Horses receiving commonly used dosages of AK and EF may benefit from administration of ASU + GLU + CS.
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