Effect of aminoguanidine, a nitric oxide synthase inhibitor, on ocular infection with herpes simplex virus in Balb/c mice.
OBJECTIVE
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 10(3) plaque-forming units (PFU)/ml; control, 0. 22 x 10(2) 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.
Benencia
F
F
Laboratory of Immunochemistry, Department of Biological Chemistry, Faculty of Sciences, University of Buenos Aires, Pabellón II, Piso 4, Ciudad Universitaria, 1428 Buenos Aires, Argentina. fbenen@qb.fcen.uba.ar
Courrèges
M C
MC
Gamba
G
G
Cavalieri
H
H
Massouh
E J
EJ
D000287:Administration, Topical; D000818:Animals; D003315:Cornea / Q000187:drug effects* / Q000201:enzymology / Q000821:virology; D004279:DNA, Viral / Q000032:analysis; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006146:Guanidines / Q000627:therapeutic use*; D018259:Herpesvirus 1, Human / Q000302:isolation & purification / Q000502:physiology; D018258:Herpesvirus 2, Human / Q000302:isolation & purification / Q000502:physiology; D016849:Keratitis, Herpetic / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009883:Ophthalmic Solutions; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012668:Trigeminal Ganglion / Q000821:virology
D004279:DNA, Viral; D004791:Enzyme Inhibitors; D006146:Guanidines; D009883:Ophthalmic Solutions; D019001:Nitric Oxide Synthase; C004479:pimagedine