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环丙沙星和皮质类固醇对小鼠鼓膜成纤维细胞的细胞毒性作用。

Cytotoxicity of Ciprofloxacin and Steroids in Mouse Tympanic Membrane Fibroblasts.

机构信息

1 Department of Otolaryngology-Head and Neck Surgery, University of Florida, Gainesville, Florida, USA.

出版信息

Otolaryngol Head Neck Surg. 2018 Mar;158(3):547-552. doi: 10.1177/0194599817751093. Epub 2018 Jan 16.

Abstract

Objective Ciprofloxacin, commonly given as eardrops, has been shown to adversely affect tympanic membrane fibroblasts. Dexamethasone potentiates this effect. A newly available eardrop contains ciprofloxacin and fluocinolone, a more potent steroid. We evaluated the cytotoxic effects of this preparation on mouse tympanic membrane fibroblasts. Study Design Prospective, in vitro. Setting Academic laboratory. Subjects and Methods In experiment 1, fibroblasts were exposed to 1:10 dilutions of commercially available 0.3% ofloxacin, 0.3% ciprofloxacin, 0.3% ciprofloxacin + 0.1% dexamethasone, 0.3% ciprofloxacin + 0.025% fluocinolone, or dilute hydrochloric acid (control), twice within 24 hours. In experiment 2, cells were also treated with the dilutions of the pure form of dexamethasone 0.1% or fluocinolone 0.025%, alone and in combination with ofloxacin or ciprofloxacin. Cells were exposed to the solutions for 2 hours each time and were placed back in growth media after the treatments. Cells were observed with phase-contrast microscope until the cytotoxicity assay was performed. Results Survival of fibroblasts treated with ofloxacin was not different from the control. Fibroblasts treated with ciprofloxacin, ciprofloxacin + dexamethasone, or ciprofloxacin + fluocinolone had much lower survival (all P < .0001). Cells treated with ciprofloxacin + fluocinolone had lower survival than ciprofloxacin ( P < .0001) and ciprofloxacin + dexamethasone ( P = .0001). Steroids alone also decreased fibroblast survival compared to control ( P < .0001). The combination of dexamethasone or fluocinolone with ciprofloxacin, but not ofloxacin, further decreased fibroblast survival ( P < .0001). Phase-contrast images mirrored the cytotoxicity findings. Conclusion Tympanic membrane fibroblast cytotoxicity of ciprofloxacin is potentiated by corticosteroids. This effect may be deleterious when treating a healing perforation but beneficial when treating granulation tissue on the tympanic membrane.

摘要

目的 环丙沙星(通常作为滴耳液使用)已被证明会对鼓膜成纤维细胞产生不良影响,而地塞米松可增强这种作用。一种新的滴耳液含有环丙沙星和氟轻松,后者是一种更强效的类固醇。我们评估了这种制剂对小鼠鼓膜成纤维细胞的细胞毒性作用。

研究设计 前瞻性,体外。

设置 学术实验室。

研究对象和方法 在实验 1 中,将成纤维细胞暴露于市售的 0.3%氧氟沙星、0.3%环丙沙星、0.3%环丙沙星+0.1%地塞米松、0.3%环丙沙星+0.025%氟轻松或稀盐酸(对照)的 1:10 稀释液中,在 24 小时内进行两次处理。在实验 2 中,还单独和联合使用 0.1%地塞米松或 0.025%氟轻松的纯形式的稀释液处理细胞,方法是每次暴露于溶液 2 小时,然后在处理后将细胞放回生长培养基中。每次处理后用相差显微镜观察细胞,直到进行细胞毒性测定。

结果 用氧氟沙星处理的成纤维细胞的存活率与对照组无差异。用环丙沙星、环丙沙星+地塞米松或环丙沙星+氟轻松处理的成纤维细胞的存活率明显较低(均 P<.0001)。用环丙沙星+氟轻松处理的细胞的存活率低于环丙沙星(P<.0001)和环丙沙星+地塞米松(P=.0001)。单独使用类固醇与对照组相比也降低了成纤维细胞的存活率(P<.0001)。地塞米松或氟轻松与环丙沙星的联合使用,但不是与氧氟沙星的联合使用,进一步降低了成纤维细胞的存活率(P<.0001)。相差显微镜图像反映了细胞毒性发现。

结论 地塞米松增强了环丙沙星对鼓膜成纤维细胞的细胞毒性。这种作用在治疗愈合性穿孔时可能是有害的,但在治疗鼓膜上的肉芽组织时可能是有益的。

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