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

Nemec, Ana; Pavlica, Zlatko; Petelin, Milan; Crossley, David A.; Šentjurc, Marjeta; Jerin, Aleš; Eržen, Damijan; Zdovc, Irena; Hitti, Tina; Skalerič, Uroš

doi:10.1016/j.archoralbio.2010.04.003

« Previous Next »Archives of Oral Biology
Volume 55, Issue 7 , Pages 509-514, July 2010

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

Nemec Ana
- Veterinary Faculty Small Animal Clinic, University of Ljubljana, Gerbičeva 60, 1115 Ljubljana, Slovenia
- Corresponding author. Current address: Dentistry & Oral Surgery Service, Veterinary Medical Teaching Hospital, University of California, Davis, One Shields Avenue, Davis, CA 95616-8747, USA. Tel.: +1 530 752 2470; fax: +1 530 752 9620.
Pavlica Zlatko
- Veterinary Faculty Small Animal Clinic, University of Ljubljana, Gerbičeva 60, 1115 Ljubljana, Slovenia
Petelin Milan
- Department for Oral Medicine and Periodontology, Faculty of Medicine, University of Ljubljana, Hrvatski trg 1, 1000 Ljubljana, Slovenia
Crossley David A.
- Veterinary Faculty Small Animal Clinic, University of Ljubljana, Gerbičeva 60, 1115 Ljubljana, Slovenia
Šentjurc Marjeta
- Jožef Stefan Institute, Jamova 39, 1000 Ljubljana, Slovenia
Jerin Aleš
- University Medical Centre Ljubljana, Institute of Clinical Chemistry and Biochemistry, Njegoševa 4, Ljubljana, Slovenia
Eržen Damijan
- University Clinic of Respiratory and Allergic Diseases Golnik, 4240 Golnik, Slovenia
Zdovc Irena
- Institute of Microbiology and Parasitology, Veterinary Faculty, University of Ljubljana, Gerbičeva 60, 1115 Ljubljana, Slovenia
Hitti Tina
- Veterinary Faculty Small Animal Clinic, University of Ljubljana, Gerbičeva 60, 1115 Ljubljana, Slovenia
Skalerič Uroš
- Department for Oral Medicine and Periodontology, Faculty of Medicine, University of Ljubljana, Hrvatski trg 1, 1000 Ljubljana, Slovenia

Accepted 7 April 2010.

Abstract

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.

Design

NOS inhibitors systemic effects were investigated in a murine chronic oral inoculation model using live Porphyromonas gingivalis ATCC 33277 (0.3ml; 10⁹cfu/ml) or sterile broth (0.3ml). 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.

Keywords: Porphyromonas gingivalis, Systemic nitric oxide, 1400W, l-NAME, Mice