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

Arquivos Brasileiros de Oftalmologia

Angelino Julio Cariello²  Gabriela Freitas Pereira De Souza¹  Márcia Serva Lowen¹  Marcelo Ganzarolli De Oliveira¹  Ana Luisa Höfling-lima² 

[1] ,Universidade Federal de São Paulo Department of Ophthalmology São Paulo SP ,Brazil

关键词: Drug toxicity;    S-nitrosothiols;    S-nitrosoglutathione;    Methylcellulose;    Nitric oxide donors;    Toxicidade de drogas;    S-nitrosotióis;    S-nitrosoglutationa;    Metilcelulose;    Doadores de óxido nítrico;   

DOI  :  10.1590/S0004-27492013000100011

来源: SciELO

【 摘 要 】

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.

【 授权许可】

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