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非甾体类抗炎眼药水对人角膜上皮细胞的体外毒性研究

The Toxicity of Nonsteroidal Anti-inflammatory Eye Drops against Human Corneal Epithelial Cells in Vitro.

作者信息

Lee Jong Soo, Kim Young Hi, Park Young Min

机构信息

Department of Ophthalmology, Pusan National University School of Medicine and Medical Research Institute, Pusan National University Hospital, Busan, Korea.

B&G Eye Clinic, Busan, Korea.

出版信息

J Korean Med Sci. 2015 Dec;30(12):1856-64. doi: 10.3346/jkms.2015.30.12.1856. Epub 2015 Nov 30.

Abstract

This study investigated the toxicity of commercial non-steroid anti-inflammatory drug (NSAID) eye solutions against corneal epithelial cells in vitro. The biologic effects of 1/100-, 1/50-, and 1/10-diluted bromfenac sodium, pranoprofen, diclofenac sodium, and the fluorometholone on corneal epithelial cells were evaluated after 1-, 4-, 12-, and 24-hr of exposure compared to corneal epithelial cell treated with balanced salt solution as control. Cellular metabolic activity, cellular damage, and morphology were assessed. Corneal epithelial cell migration was quantified by the scratch-wound assay. Compared to bromfenac and pranoprofen, the cellular metabolic activity of diclofenac and fluorometholone significantly decreased after 12-hr exposure, which was maintained for 24-hr compared to control. Especially, at 1/10-diluted eye solution for 24-hr exposure, the LDH titers of fluorometholone and diclofenac sodium markedly increased more than those of bromfenac and pranoprofen. In diclofenac sodium, the Na(+) concentration was lower and amount of preservatives was higher than other NSAIDs eye solutions tested. However, the K(+) and Cl(-) concentration, pH, and osmolarity were similar for all NSAIDs eye solutions. Bromfenac and pranoprofen significantly promoted cell migration, and restored wound gap after 48-hr exposure, compared with that of diclofenac or fluorometholone. At 1/50-diluted eye solution for 48-hr exposure, the corneal epithelial cellular morphology of diclofenac and fluorometholone induced more damage than that of bromfenac or pranoprofen. Overall, the corneal epithelial cells in bromfenac and pranoprofen NSAID eye solutions are less damaged compared to those in diclofenac, included fluorometholone as steroid eye solution.

摘要

本研究调查了市售非甾体抗炎药(NSAID)眼药水对体外角膜上皮细胞的毒性。将1/100、1/50和1/10稀释的溴芬酸钠、普拉洛芬、双氯芬酸钠以及氟米龙与用平衡盐溶液处理的角膜上皮细胞作为对照,在暴露1、4、12和24小时后,评估它们对角膜上皮细胞的生物学效应。评估细胞代谢活性、细胞损伤和形态。通过划痕试验对角膜上皮细胞迁移进行定量分析。与溴芬酸和普拉洛芬相比,双氯芬酸和氟米龙在暴露12小时后细胞代谢活性显著降低,与对照组相比持续24小时。特别是,在1/10稀释的眼药水暴露24小时时,氟米龙和双氯芬酸钠的乳酸脱氢酶(LDH)滴度比溴芬酸和普拉洛芬显著升高。在双氯芬酸钠中,Na(+)浓度较低,防腐剂含量高于其他测试的NSAID眼药水。然而,所有NSAID眼药水的K(+)和Cl(-)浓度、pH值和渗透压相似。与双氯芬酸或氟米龙相比,溴芬酸和普拉洛芬在暴露48小时后显著促进细胞迁移并修复伤口间隙。在1/50稀释的眼药水暴露48小时时,双氯芬酸和氟米龙诱导的角膜上皮细胞形态损伤比溴芬酸或普拉洛芬更严重。总体而言,与双氯芬酸(包括作为类固醇眼药水的氟米龙)相比,溴芬酸和普拉洛芬NSAID眼药水对角膜上皮细胞的损伤较小。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae6a/4689832/97741efe8ccc/jkms-30-1856-g001.jpg

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