Assessment of ocular surface toxicity after topical instillation of nitric oxide donors

PURPOSE: To evaluate the ocular surface toxicity of two nitric oxide donors in ex vivo and in vivo animal models: S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylcysteine (SNAC) in a hydroxypropyl methylcellulose (HPMC) matrix at final concentrations 1.0 and 10.0 mM. METHODS: Ex vivo GSNO and SNAC toxicities were clinically and histologically analyzed using freshly excised pig eyeballs. In vivo experiments were performed with 20 albino rabbits which were randomized into 4 groups (5 animals each): Groups 1 and 2 received instillations of 150 µL of aqueous HPMC solution containing GSNO 1.0 and 10.0 mM, respectively, in one of the eyes; Groups 3 and 4 received instillations of 150 µL of aqueous HPMC solution-containing SNAC 1.0 and 10.0 mM, respectively, in one of the eyes. The contralateral eyes in each group received aqueous HPMC as a control. All animals underwent clinical evaluation on a slit lamp and the eyes were scored according to a modified Draize eye test and were histologically analyzed. RESULTS: Pig eyeballs showed no signs of perforation, erosion, corneal opacity or other gross damage. These findings were confirmed by histological analysis. There was no difference between control and treated rabbit eyes according to the Draize eye test score in all groups (p>0.05). All formulations showed a mean score under 1 and were classified as "non-irritating". There was no evidence of tissue toxicity in the histological analysis in all animals. CONCLUSION: Aqueous HPMC solutions containing GSNO and SNAC at concentrations up to 10.0 mM do not induce ocular irritation.

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Main Authors: Cariello,Angelino Julio, Souza,Gabriela Freitas Pereira de, Lowen,Márcia Serva, Oliveira,Marcelo Ganzarolli de, Höfling-Lima,Ana Luisa
Format: Digital revista
Language:English
Published: Conselho Brasileiro de Oftalmologia 2013
Online Access:http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0004-27492013000100011
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spelling oai:scielo:S0004-274920130001000112013-06-25Assessment of ocular surface toxicity after topical instillation of nitric oxide donorsCariello,Angelino JulioSouza,Gabriela Freitas Pereira deLowen,Márcia ServaOliveira,Marcelo Ganzarolli deHöfling-Lima,Ana Luisa Drug toxicity S-nitrosothiols S-nitrosoglutathione Methylcellulose Nitric oxide donors PURPOSE: To evaluate the ocular surface toxicity of two nitric oxide donors in ex vivo and in vivo animal models: S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylcysteine (SNAC) in a hydroxypropyl methylcellulose (HPMC) matrix at final concentrations 1.0 and 10.0 mM. METHODS: Ex vivo GSNO and SNAC toxicities were clinically and histologically analyzed using freshly excised pig eyeballs. In vivo experiments were performed with 20 albino rabbits which were randomized into 4 groups (5 animals each): Groups 1 and 2 received instillations of 150 µL of aqueous HPMC solution containing GSNO 1.0 and 10.0 mM, respectively, in one of the eyes; Groups 3 and 4 received instillations of 150 µL of aqueous HPMC solution-containing SNAC 1.0 and 10.0 mM, respectively, in one of the eyes. The contralateral eyes in each group received aqueous HPMC as a control. All animals underwent clinical evaluation on a slit lamp and the eyes were scored according to a modified Draize eye test and were histologically analyzed. RESULTS: Pig eyeballs showed no signs of perforation, erosion, corneal opacity or other gross damage. These findings were confirmed by histological analysis. There was no difference between control and treated rabbit eyes according to the Draize eye test score in all groups (p>0.05). All formulations showed a mean score under 1 and were classified as "non-irritating". There was no evidence of tissue toxicity in the histological analysis in all animals. CONCLUSION: Aqueous HPMC solutions containing GSNO and SNAC at concentrations up to 10.0 mM do not induce ocular irritation.info:eu-repo/semantics/openAccessConselho Brasileiro de OftalmologiaArquivos Brasileiros de Oftalmologia v.76 n.1 20132013-02-01info:eu-repo/semantics/articletext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0004-27492013000100011en10.1590/S0004-27492013000100011
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countrycode BR
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region America del Sur
libraryname SciELO
language English
format Digital
author Cariello,Angelino Julio
Souza,Gabriela Freitas Pereira de
Lowen,Márcia Serva
Oliveira,Marcelo Ganzarolli de
Höfling-Lima,Ana Luisa
spellingShingle Cariello,Angelino Julio
Souza,Gabriela Freitas Pereira de
Lowen,Márcia Serva
Oliveira,Marcelo Ganzarolli de
Höfling-Lima,Ana Luisa
Assessment of ocular surface toxicity after topical instillation of nitric oxide donors
author_facet Cariello,Angelino Julio
Souza,Gabriela Freitas Pereira de
Lowen,Márcia Serva
Oliveira,Marcelo Ganzarolli de
Höfling-Lima,Ana Luisa
author_sort Cariello,Angelino Julio
title Assessment of ocular surface toxicity after topical instillation of nitric oxide donors
title_short Assessment of ocular surface toxicity after topical instillation of nitric oxide donors
title_full Assessment of ocular surface toxicity after topical instillation of nitric oxide donors
title_fullStr Assessment of ocular surface toxicity after topical instillation of nitric oxide donors
title_full_unstemmed Assessment of ocular surface toxicity after topical instillation of nitric oxide donors
title_sort assessment of ocular surface toxicity after topical instillation of nitric oxide donors
description PURPOSE: To evaluate the ocular surface toxicity of two nitric oxide donors in ex vivo and in vivo animal models: S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylcysteine (SNAC) in a hydroxypropyl methylcellulose (HPMC) matrix at final concentrations 1.0 and 10.0 mM. METHODS: Ex vivo GSNO and SNAC toxicities were clinically and histologically analyzed using freshly excised pig eyeballs. In vivo experiments were performed with 20 albino rabbits which were randomized into 4 groups (5 animals each): Groups 1 and 2 received instillations of 150 µL of aqueous HPMC solution containing GSNO 1.0 and 10.0 mM, respectively, in one of the eyes; Groups 3 and 4 received instillations of 150 µL of aqueous HPMC solution-containing SNAC 1.0 and 10.0 mM, respectively, in one of the eyes. The contralateral eyes in each group received aqueous HPMC as a control. All animals underwent clinical evaluation on a slit lamp and the eyes were scored according to a modified Draize eye test and were histologically analyzed. RESULTS: Pig eyeballs showed no signs of perforation, erosion, corneal opacity or other gross damage. These findings were confirmed by histological analysis. There was no difference between control and treated rabbit eyes according to the Draize eye test score in all groups (p>0.05). All formulations showed a mean score under 1 and were classified as "non-irritating". There was no evidence of tissue toxicity in the histological analysis in all animals. CONCLUSION: Aqueous HPMC solutions containing GSNO and SNAC at concentrations up to 10.0 mM do not induce ocular irritation.
publisher Conselho Brasileiro de Oftalmologia
publishDate 2013
url http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0004-27492013000100011
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