Comparison of toxicities of moxifloxacin, cefuroxime, and levofloxacin to corneal endothelial cells in vitro

Comparison of toxicities of moxifloxacin, cefuroxime, and levofloxacin to corneal endothelial cells in vitro
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DOI:
10.1016/j.jcrs.2014.08.027
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发表时间:
2014-11-01
影响因子:
2.8
通讯作者:
Yamagami, Satoru
Yamagami, Satoru
中科院分区:
医学2区
文献类型:
--
作者:
Haruki, Tomoko;Miyazaki, Dai;Yamagami, Satoru

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目得:评价和比较利多卡因、头孢呋辛和左氧氟沙星对体外培养的人角膜内皮细胞的毒性作用,并确定其安全的前房内浓度。单位:鸟取大学,鸟取,日本。设计:实验研究。方法:培养的人角膜内皮细胞暴露于利多卡因、头孢呋辛和左氧氟沙星,浓度高达2000 μ g/mL。通过乙锭同二聚体-1摄取和细胞活力,通过内在酯酶活性来确定膜损伤的评价。结果:3种抗生素对人角膜内皮细胞组成性分泌白细胞介素-6(IL-6)的抑制作用(6 h)均呈剂量依赖性,其中尤以利福沙星和左氧氟沙星(>= 500 μ g/mL)作用最强。对于头孢呋辛,在浓度高于500 μ g/mL时,6小时未观察到膜损伤,24小时仅检测到轻微损伤。利福沙星、左氧氟沙星和头孢呋辛对细胞活力的半最大抑制浓度分别为487 μ g/mL、578 μ g/mL和1600 μ g/mL。3种抗生素对IL-6组成性分泌的抑制作用在15.6 μ g/mL或更高时观察到,表明抗生素即使在低浓度下也会损害保护性细胞因子的分泌。结论:莫西沙星在超过500 μ g/mL时会对角膜内皮细胞的细胞膜造成损伤;更高的浓度会降低细胞活力。考虑到阿替沙星抑制90%生长的最低抑制浓度较低,推荐前房内注射500 μ g/mL或更低的阿替沙星用于预防性使用。
PURPOSE: To evaluate and compare the toxic effects of moxifloxacin, cefuroxime, and levofloxacin on human corneal endothelial cells in vitro and determine the safe intracameral concentrations for them.SETTING: Tottori University, Tottori, Japan.DESIGN: Experimental study.METHODS: Human corneal endothelial cells in culture were exposed to moxifloxacin, cefuroxime, and levofloxacin at concentrations up to 2000 mu g/mL. Evaluation of membrane damage was determined by ethidium homodimer-1 uptake and cell viability, by intrinsic esterase activity. The inhibitory effects of the 3 antibiotics on the constitutive secretion of interleukin-6 (IL-6) by human corneal endothelial cells were determined by enzyme-linked immunosorbent assay.RESULTS: The acute effects (6 hour) of the 3 antibiotics on membrane damage and cell death were dose-dependent for moxifloxacin and levofloxacin (>= 500 mu g/mL). For cefuroxime, membrane damage was not observed at 6 hours and only slight damage was detected at 24 hours at concentrations higher than 500 mu g/mL. The half maximum inhibitory concentrations on cell viability of moxifloxacin, levofloxacin, and cefuroxime were 487 mu g/mL, 578 mu g/mL, and 1600 mu g/mL, respectively. The inhibitory effects of the 3 antibiotics on the constitutive secretion of IL-6 were observed at 15.6 mu g/mL or higher, indicating the antibiotics can impair the secretion of the protective cytokine even at low concentrations.CONCLUSIONS: Moxifloxacin at more than 500 mu g/mL caused damage to the cell membranes of corneal endothelial cells; even higher concentrations decreased cell viability. Considering the lower minimum inhibitory concentration for inhibiting 90% growth by moxifloxacin, intracameral moxifloxacin at 500 mu g/mL or less is recommended for prophylactic use.