title: The Toxicity of Nonsteroidal Anti-inflammatory Eye Drops against Human Corneal Epithelial Cells in Vitro.
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.
authors.affiliation: Department of Ophthalmology, Pusan National University School of Medicine and Medical Research Institute, Pusan National University Hospital, Busan, Korea.
authors.forename: Jong Soo
authors.identifier: 0000-0002-1052-2924
authors.initials: JS
authors.lastname: Lee
authors.affiliation: B&G Eye Clinic, Busan, Korea.
authors.forename: Young Hi
authors.identifier: 0000-0001-8787-2175
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Ophthalmology, Pusan National University School of Medicine and Medical Research Institute, Yangsan Pusan National University Hospital, Yangsan, Korea.
authors.forename: Young Min
authors.identifier: 0000-0001-8495-9224
authors.initials: YM
authors.lastname: Park
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000633:toxicity*; D001577:Benzophenones / Q000008:administration & dosage / Q000633:toxicity; D001578:Benzopyrans / Q000008:administration & dosage / Q000633:toxicity; D001969:Bromobenzenes / Q000008:administration & dosage / Q000633:toxicity; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004008:Diclofenac / Q000008:administration & dosage / Q000633:toxicity; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D019573:Epithelium, Corneal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005469:Fluorometholone / Q000008:administration & dosage / Q000633:toxicity; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D009883:Ophthalmic Solutions; D011422:Propionates / Q000008:administration & dosage / Q000633:toxicity
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001577:Benzophenones; D001578:Benzopyrans; D001969:Bromobenzenes; D009883:Ophthalmic Solutions; D011422:Propionates; D004008:Diclofenac; C043940:pyranoprofen; C053083:bromfenac; D007770:L-Lactate Dehydrogenase; D005469:Fluorometholone
keywords: Bromfenac Sodium; Corneal Epithelial Cells; Cytotoxicity; Diclofenac Sodium; Fluorometholone; Pranoprofen