title: Protective effects of fluoroquinolones on UV-induced damage of cultured ocular cell lines.
abstract: Although the fluoroquinolones have strong antibacterial effects, some of them also have adverse ocular effects such as diplopia, uveitis, optic neuropathy, and retinal detachment. The purpose of this study was to determine whether low concentrations of fluoroquinolones can lessen the cytotoxic effects of ultraviolet (UV) light on different kinds of cultured ocular cells. We studied cultured human corneal endothelial cells (HCECs), a retinal ganglion cell line (RGC-5), a mouse-derived photoreceptor cell line (661W), a human adult retinal pigment epithelial cell line (ARPE-19), primary retinal cells, and primary human RPE cells. Levofloxacin, ciprofloxacin, and clinafloxacin were selected as the fluoroquinolones to test. The viabilities of the 661W, ARPE-19, and hRPE cells were assessed by Cell Counting Kit-8, and that of HCECs, 661W cells, and ARPE-19 cells by double fluorescent staining with Hoechst 33342 and propidium iodide (PI). Damage of retinal primary culture cells was assessed by immunostaining. Intracellular production of reactive oxygen species was measured in ARPE-19 cells by CM-H2DCFDA after UV light exposure. An activation of caspase by UV light in ARPE-19 cells was detected with a caspase-3/7 assay kit. UV exposure increased the number of dead cells, and the three fluoroquinolones tested suppressed this increase. Fluoroquinolones also protected the cells against the hydroxyperoxide (H2O2)-induced cell damage. Moreover, the fluoroquinolones decreased the production of reactive oxygen species and the activity of caspase-3/7, and low concentrations of fluoroquinolones reduced the oxidative stress in cultured ocular cell lines. We conclude that fluoroquinolones may have protective effects in these cells against UV exposure.
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan; Department of Ophthalmology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nishida
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kuse
authors.affiliation: Department of Ophthalmology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Mochizuki
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Shimazawa
authors.affiliation: Department of Ophthalmology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan. Electronic address: hidehara@gifu-pu.ac.jp.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hara
mesh_terms: D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D019610:Cytoprotection / Q000187:drug effects / Q000528:radiation effects; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D005123:Eye / Q000166:cytology*; D024841:Fluoroquinolones / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D024841:Fluoroquinolones; D016166:Free Radical Scavengers; D011837:Radiation-Protective Agents; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D053148:Caspase 3; D053179:Caspase 7
keywords: Fluoroquinolone; Oxidative stress; Reactive oxygen species; Retinal pigment epithelium