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Effect of Aminoguanidine, a Nitric Oxide Synthase Inhibitor, on Ocular Infection with Herpes Simplex Virus in Balb/c Mice

¹ From the Laboratory of Immunochemistry, Department of Biological Chemistry, Faculty of Sciences, and the ² Laboratory of Experimental Pathology, Department of Pathology, Faculty of Medicine, University of Buenos Aires, Argentina.

PURPOSE. To study the effect of aminoguanidine (AMG), an inhibitor of nitric oxide production, on the ocular infection of Balb/c mice with herpes simplex virus (HSV) type 1 strain F and HSV-2 strain G.

METHODS. Animals were treated with different amounts of AMG (0.5, 0.1, and 0.05 mg/mouse) by topical application in the eye from postinfection (PI) days -2 through +5, considering 0 the day of infection. At different PI days, development of herpetic keratitis was evaluated in treated and control mice.

RESULTS. Treated animals showed a dose-dependent increase in ocular disease after viral infection, compared with control animals. Viral titers in ocular washings were higher in AMG-treated mice (PI day 2, HSV-1: AMG 0.5 mg, 1.3 x 10³ plaque-forming units (PFU)/ml; control, 0. 22 x 10² PFU/ml, P < 0.025). At PI day 3, control corneas had only scattered inflammatory cells, whereas those from treated animals showed a conspicuous infiltrate consisting primarily of neutrophils. Viral titers were also higher in brains of treated mice. These animals died earlier and in a greater proportion than control animals (percentage of mortality, PI day 12, HSV-1: AMG 0.5 mg, 40% ± 4%; control, 18% ± 3%, P < 0.05).

CONCLUSIONS. These data indicate an inhibitory effect of nitric oxide on HSV ocular infection.

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