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

Abstract

Ethic committee from UNIFESP: number 1573/08. ABSTRACTPurpose: 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-Nace tylcysteine (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 ana lyzed 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. The re 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.

Effect of Nitric Oxide onAcanthamoeba castellanii

“…35 The in vivo safety of different NO donors, such as S-nitrosoglutathione and S-nitroso-Nacetylcysteine, was also demonstrated up to 10 mM concentration in rabbit eyes. 36 In contrast, we observed that SNP exposure showed a dose dependent and significant cytotoxic effect on HCEC even with a relatively low concentration (1 lM). This finding is consistent with the previous report that SNP ( 500 lM) was toxic to mammalian cells.…”

Genipin in an Ex Vivo Corneal Model of Bacterial and Fungal Keratitis

“…The chemosis, lids closed/open, swelling, discharge and redness of the conjunctiva were graded on a scale from 0 to 3; iris (swelling and hyperemia) was graded on a scale from 0 to 2; and cornea (irritation, opacity until ulceration) was graded on a scale from 0 to 4, as previously described. 94 , 95 In accordance with the UN GHS/ European Union Regulation on Classification, Labelling and Packaging classification system, the sum of the score was then used to classify genipin based on the severity of effects and timing of reversibility of effects. 94 , 95 …”

“… 94 , 95 In accordance with the UN GHS/ European Union Regulation on Classification, Labelling and Packaging classification system, the sum of the score was then used to classify genipin based on the severity of effects and timing of reversibility of effects. 94 , 95 …”

S-Nitrosoglutathione Accelerates Recovery from 5-Fluorouracil-Induced Oral Mucositis

“…It is also capable of transnitrosating cysteine residues of proteins and exerts a marked microbicidal action [20] , [21] . These combined properties of GSNO, in addition to its miscibility in non-toxic and mucoadhesive hydroxypropyl methylcellulose (HPMC; a pharmaceutical vehicle) [22] , make HPMC/GSNO formulations a promising option for investigating the effects of local NO-donor administration on the course of 5-fluorouracil (5-FU)-induced oral mucositis, which is the purpose of the present study.…”