Nuzzi Raffaele1, Alessandro Marchese2, Dario Ghigo3. 1. Division of Ophthalmology, Department of Surgical Sciences, University of Turin, San Luigi Gonzaga Hospital, Regione Gonzole 10, 10043, Orbassano, TO, Italy. 2. Division of Ophthalmology, Department of Surgical Sciences, University of Turin, San Luigi Gonzaga Hospital, Regione Gonzole 10, 10043, Orbassano, TO, Italy. amarchese@hotmail.it. 3. Department of Oncology, University of Turin, Turin, Italy.
Abstract
PURPOSE: The aim of this study is to determine if dexamethasone, prednisolone and triamcinolone acetonide (TA), three anti-inflammatory drugs commonly used for ocular treatments, could affect the oxidative status of cultured human cells of the retinal pigment epithelium (RPE) and protect them against oxidative injury. METHODS: ARPE-19 cells were used as an in vitro model of RPE. Glutathione (GSH) levels were assessed to evaluate the effects of dexamethasone, prednisolone and triamcinolone on cellular antioxidant status. Oxidative stress was induced in ARPE-19 cells by treatment with the oxidizing agent menadione, and the effects of dexamethasone, prednisolone and triamcinolone were evaluated. Release of lactate dehydrogenase (LDH) in the culture medium was used to measure cytotoxicity. RESULTS: Incubation with triamcinolone or prednisolone was not able to revert menadione-induced cytotoxicity and GSH depletion; furthermore, it significantly decreased GSH levels in ARPE-19 cells (nmol of GSH/mg cellular protein: 99.7 ± 0.1 in untreated controls vs. 52.6 ± 5.2 with triamcinolone vs. 77.6 ± 5.2 with prednisolone; p < 0.001). Treatment with dexamethasone protected ARPE-19 cells from cytotoxicity and oxidative damage: lactate dehydrogenase release and GSH depletion were significantly decreased after incubation with this compound (LDHout/LDHtot: 0.221 ± 0.038 with menadione vs. 0.041 ± 0.007 with menadione + dexamethasone; p < 0.001; nmol of GSH/mg cellular protein: 5.7 ± 4.2 with menadione vs. 53.2 ± 6.1 with menadione + dexamethasone, respectively; p < 0.001) and did not induce GSH depletion (nmol of GSH/mg cellular protein: 99.7 ± 0.1 vs. 86.5 ± 8.1 nmol/min/mg prot with dexamethasone; p > 0.05). CONCLUSIONS: Dexamethasone, besides suppressing intraocular inflammation, may protect human RPE cells from oxidative stress and decrease the oxidation rate of GSH. Triamcinolone and prednisolone, inducing GSH depletion, may contribute to reduce antioxidant capacity of ARPE-19 cells.
PURPOSE: The aim of this study is to determine if dexamethasone, prednisolone and triamcinolone acetonide (TA), three anti-inflammatory drugs commonly used for ocular treatments, could affect the oxidative status of cultured human cells of the retinal pigment epithelium (RPE) and protect them against oxidative injury. METHODS: ARPE-19 cells were used as an in vitro model of RPE. Glutathione (GSH) levels were assessed to evaluate the effects of dexamethasone, prednisolone and triamcinolone on cellular antioxidant status. Oxidative stress was induced in ARPE-19 cells by treatment with the oxidizing agent menadione, and the effects of dexamethasone, prednisolone and triamcinolone were evaluated. Release of lactate dehydrogenase (LDH) in the culture medium was used to measure cytotoxicity. RESULTS: Incubation with triamcinolone or prednisolone was not able to revert menadione-induced cytotoxicity and GSH depletion; furthermore, it significantly decreased GSH levels in ARPE-19 cells (nmol of GSH/mg cellular protein: 99.7 ± 0.1 in untreated controls vs. 52.6 ± 5.2 with triamcinolone vs. 77.6 ± 5.2 with prednisolone; p < 0.001). Treatment with dexamethasone protected ARPE-19 cells from cytotoxicity and oxidative damage: lactate dehydrogenase release and GSH depletion were significantly decreased after incubation with this compound (LDHout/LDHtot: 0.221 ± 0.038 with menadione vs. 0.041 ± 0.007 with menadione + dexamethasone; p < 0.001; nmol of GSH/mg cellular protein: 5.7 ± 4.2 with menadione vs. 53.2 ± 6.1 with menadione + dexamethasone, respectively; p < 0.001) and did not induce GSH depletion (nmol of GSH/mg cellular protein: 99.7 ± 0.1 vs. 86.5 ± 8.1 nmol/min/mg prot with dexamethasone; p > 0.05). CONCLUSIONS:Dexamethasone, besides suppressing intraocular inflammation, may protect human RPE cells from oxidative stress and decrease the oxidation rate of GSH. Triamcinolone and prednisolone, inducing GSH depletion, may contribute to reduce antioxidant capacity of ARPE-19 cells.
Authors: P S Samiec; C Drews-Botsch; E W Flagg; J C Kurtz; P Sternberg; R L Reed; D P Jones Journal: Free Radic Biol Med Date: 1998-03-15 Impact factor: 7.376
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