Systemic use of selective iNOS inhibitor 1400W or non-selective NOS inhibitor l-NAME differently affects systemic nitric oxide formation after oral Porphyromonas gingivalis inoculation in mice.
OBJECTIVE
Nitric oxide synthase (NOS) inhibitors are reported to protect against the local tissue damage in gingivitis and periodontal disease by reducing nitroxidative stress during inflammation, but their systemic effects are not well investigated.


METHODS
NOS inhibitors systemic effects were investigated in a murine chronic oral inoculation model using live Porphyromonas gingivalis ATCC 33277 (0.3 ml; 10(9)cfu/ml) or sterile broth (0.3 ml). Organ nitric oxide (NO) and plasma nitrite/nitrate (NOx) were determined in mice treated with non-selective NOS inhibitor l-NAME (50mg/kg/24h i.p.) or selective iNOS inhibitor 1400W (10mg/kg/6h i.p.) for the last 5 days of the experiment. Differences between groups were evaluated by nonparametric Wilcoxon's rank-sum one-sided two-sample test and the results compared to those obtained from sham-treated (sterile broth) sham-inoculated animals (water for injection i.p./6h).


RESULTS
Repeated ingestion of P. gingivalis resulted in generalized production of NO in organs and NOx in plasma, the levels of both typically being reduced in P. gingivalis-inoculated-1400W-treated mice, whilst the use of l-NAME was largerly ineffective, even promoting NO/NOx formation. Application of either inhibitor to sham-inoculated animals enhanced NO/NOx formation, due only in part to the repeated i.p. injections.


CONCLUSIONS
The systemic use of 1400W or l-NAME differently affects systemic nitric oxide formation in mice orally challenged with P. gingivalis, but the sequelae of such an intervention should be evaluated further.
Nemec
Ana
A
University of Ljubljana, Gerbiceva, Slovenia. anemec@ucdavis.edu
Pavlica
Zlatko
Z
Petelin
Milan
M
Crossley
David A
DA
Sentjurc
Marjeta
M
Jerin
Ales
A
Erzen
Damijan
D
Zdovc
Irena
I
Hitti
Tina
T
Skaleric
Uros
U
D000578:Amidines / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D001596:Benzylamines / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D016166:Free Radical Scavengers / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D009055:Mouth / Q000382:microbiology*; D009061:Mouth Mucosa / Q000382:microbiology; D009206:Myocardium / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D009573:Nitrites / Q000097:blood; D016966:Porphyromonas gingivalis / Q000502:physiology*; D011897:Random Allocation; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution
D000578:Amidines; D001596:Benzylamines; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D019331:NG-Nitroarginine Methyl Ester