Oxidative stress in corneal tissue in experimental keratitis due to Aspergillus flavus: Effect of topical voriconazole therapy

Abstract

Abstract The present study sought to determine whether topical voriconazole exerts antioxidative effects in experimental Aspergillus flavus keratitis. Three groups of five each young albino rabbits were used. Experimental keratitis was induced by application of Aspergillus flavus conidia to scarified cornea (right eye) of 10 rabbits (another 5 rabbits were negative controls [Group I]). Five days later, A. flavus-infected animals began receiving hourly topical saline (Group II) or voriconazole (10 mg/mL) (Group III). Twenty days post-inoculation, corneal lesions were graded; expression of interleukin-1beta (IL-1β) and tumor necrosis factor-α (TNF-α) genes, activities of three enzymatic antioxidants and reduced glutathione (GSH); malondialdehyde (MDA) levels were measured in corneal homogenates. Clinical, histopathological and microbiological scores suggested most severe keratitis in Group II and least severe in Group I rabbits. mRNA transcript levels of IL-1β and TNF-α were significantly higher in Group II than in Groups III and I rabbit corneal samples. Activities/levels of enzymatic antioxidants and of GSH were lowest in Group II and highest in Group I corneal samples, and MDA level was highest in Group II and least in Group I corneal samples. Corneal oxidative stress was more intense in A. flavus-challenged, saline-treated than in A. flavus-challenged, voriconazole-treated rabbits. Topical voriconazole notably reduced severity of keratitis and oxidative stress, although infection and inflammation did not completely resolve. Voriconazole thus exerts antioxidative effects, in addition to antifungal activity, in experimental A. flavus keratitis.