IOVS Proceedings of the National Academy of Sciences
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(Investigative Ophthalmology and Visual Science. 2001;42:1277-1284.)
© 2001 by The Association for Research in Vision and Ophthalmology, Inc.

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

Fabián Benencia1,3, María C. Courrèges2, Gisela Gamba1, Hernán Cavalieri1 and Ernesto J. Massouh1

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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