Total salivary nitrates and nitrites in oral health and periodontal disease
Abstract
It is well known that nitrites are increased in saliva from patients with periodontal disease. In the oral cavity, nitrites may derive partly from the reduction of nitrates by oral bacteria. Nitrates have been reported as a defence-related mechanism. Thus, the aim of the present study was to determine the salivary levels of total nitrate and nitrite and their relationship, in unstimulated and stimulated saliva from periodontal healthy subjects, and from patients with chronic periodontal disease. Nitrates and nitrites were determined in saliva from thirty healthy subjects and forty-four patients with periodontal disease. A significant increase in salivary nitrates and nitrites was observed. Nitrates and nitrites concentration was related to clinical attachment level (CAL). A positive and significant Pearson's correlation was found between salivary total nitrates and nitrites. Periodontal treatment induced clinical improvement and decreased nitrates and nitrites. It is concluded that salivary nitrates and nitrites increase, in patients with periodontal disease, could be related to defence mechanisms. The possibility that the salivary glands respond to oral infectious diseases by increasing nitrate secretion should be explored further.
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The nitrate-nitrite-NO pathway is affected by microbial diversity and oral pathology.
“Indeed, even the nitrate-nitrite-NO pathway is affected by microbial diversity[190] and oral pathology[191–193].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [193]
Nitrite and nitrate are important protective elements of the oral and mucosal immune response, especially in settings of stress and periodontal injury.
“For instance, nitrite and nitrate are important protective elements of the oral and mucosal immune response, especially in settings of stress and periodontal injury[86,193,231].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [193]
Areas that have high nitrate reductase activity such as the dorsum of the tongue, gingival plaque and periodontal pockets demonstrate low relative oxygen concentrations (8-13 mmHg, ~1-2%).
“Conversely, areas that have high nitrate reductase activity such as the dorsum of the tongue, gingival plaque and periodontal pockets demonstrate low relative oxygen concentrations (8–13 mmHg, ~1–2%)[81,193,201,266].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [193]
In the setting of salivary gland dysfunction, there is a decrease in salivary nitrate concentration and corollary increase in urinary excretion, thereby reducing total body nitrate content and its enterosalivary circulation.
“In the setting of salivary gland dysfunction, there is a decrease in salivary nitrate concentration and corollary increase in urinary excretion, thereby reducing total body nitrate content and its enterosalivary circulation[84,193,231,293].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [193]
Nitrate content in saliva is highly regulated.
“Nitrate content in saliva is highly regulated[85,86,193,231].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [193]
Both salivary nitrate and nitrite concentrations and gingival expression of NO-forming NOS have been found to be increased in periodontal disease, which also tend to increase with disease severity and improve with periodontal treatment.
“Interestingly, both salivary nitrate and nitrite concentrations and gingival expression of NO-forming NOS have been found to be increased in periodontal disease, which also tend to increase with disease severity and improve with periodontal treatment[99,193,291,292].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [193]
Inflammation in the localized anaerobic environment of the expanding subgingival crypts, in concert with high salivary nitrate, likely selects for survival and growth of the anaerobic, nitrate-reducing bacteria typical of periodontal disease.
“What is clear is that inflammation in the localized anaerobic environment of the expanding subgingival crypts, in concert with high salivary nitrate, likely selects for survival and growth of the anaerobic, nitrate-reducing bacteria typical of periodontal disease[193].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [193]
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Ecological Modulation of Oral Biofilms: Novel Approaches to Treat and Prevent Oral Diseases
Parga, A., & Otero, A. (2025) · Springer series on biofilms · doi:10.1007/978-3-031-82202-5_22
Романенко, О. Г., Komskyi, M. P., Ейсмунд, П. А., Хотімська, Ю. В., Lavreniuk, Y. V., Голуб, А. В., Samoilenko, I. I., & Салюк, О. Д. (2025) · Інновації в стоматології · doi:10.35220/2523-420x/2025.2.15
Guo, K., JOSHIPURA, K. J., Ricart, K. C., Patel, R. P., & Morou-Bermúdez, E. (2026) · Archives of Oral Biology · doi:10.1016/j.archoralbio.2026.106660
- Authors
- Sánchez, G. A., Miozza, V. A., Delgado, A., & Busch, L.
- Affiliations
- Universidad de Buenos Aires (AR)
- Corresponding author
- Sánchez, Gabriel A.
- Venue
- Nitric Oxide
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 36
- Pages
- 31-35
- ISSN
- 1089-8603 (ISSN-L)
- OpenAlex
- W2024576523
- Cited by
- 64
- References
- 30
- Citations by year
- 2026: 2 · 2025: 10 · 2024: 9 · 2023: 4 · 2022: 6 · 2021: 5 · 2020: 4 · 2019: 6 · 2018: 4 · 2017: 4 · 2016: 7 · 2015: 2 · 2014: 1
- FWCI
- 4.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nitric Oxide (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Buenos Aires (UBACyT 20020090200475)
- Topics
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Health Sciences › Medicine › Physiology › Salivary Gland Disorders and Functions
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- salivary nitrate, salivary nitrite, periodontal disease, chronic periodontitis, clinical attachment level, oral bacteria, nitrate reduction, periodontal treatment, unstimulated saliva, stimulated saliva
- MeSH terms
- Adult, Female, Humans, Male, Mouth, Nitrates, Nitrites, Oral Health, Periodontal Diseases, Regression Analysis, Saliva, Case-Control Studies
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