Nitric oxide formation in the metabolism of nitrates in the oral cavity

Authors

  • Ye. H. Romanenko State Institution "Dnipropetrovsk Medical Academy of the Ministry of health of Ukraine", Dnipro,
  • L. V. Hryhorenko State Institution "Dnipropetrovsk Medical Academy of the Ministry of health of Ukraine", Dnipro,
  • M. P. Komskyi Dnipropetrovsk Medical Institute of Traditional and Non-traditional Medicine, Dnipro, Ukraine,
  • P. L. Sribnyk State Institution "Dnipropetrovsk Medical Academy of the Ministry of health of Ukraine", Dnipro,
  • O. O. Sinkovska State Institution "Dnipropetrovsk Medical Academy of the Ministry of health of Ukraine", Dnipro,

DOI:

https://doi.org/10.14739/2310-1210.2019.5.179472

Keywords:

nitric oxide, oral cavity, oral bacteria, nitrate, nitrate reductase, nitrite, nitrite reductase, saliva, nutrition, systemic diseases

Abstract

 

Nowadays, nitric oxide is recognized as a regulator of important vascular and metabolic functions. Nitric oxide is formed in the endothelium by converting essential amino acid L-arginine to L-citrulline with the participation of constitutional endothelial nitric oxide synthase. In addition to endogenous pathway of formation, dietary nitrate contributes to the nitric oxide generation through the successive stages (NO3-NO2-NO) mediated by salivary glands and bacteria of the oral cavity.

Purpose of the research – to demonstrate modern scientific data focused on a role of salivary glands and bacteria in nitrates metabolism and maintenance of nitric oxide homeostasis.

Results of the studies show that in the oral cavity, there are synanthropic facultative anaerobic bacteria which possess nitrate reductase enzymes and reduce nitrates to nitrites. In the acidic environment of the stomach, nitrites undergo non-enzymatic disproportionation, followed by the formation of nitric oxide and other nitrogen compounds which are involved in the regulation of important biological functions. Dietary nitrites and nitrates can be rapidly absorbed from the upper gastrointestinal tract into the systemic bloodstream and serve as effective donors of nitric oxide in a case of physiological hypoxia. This mechanism of nitric oxide formation is called “enterosalivary nitrate-nitrite-nitric oxide pathway”. The review presents a cardioprotective effect of regular consumption of dietary nitrate-rich products. Diagnostic markers of nitric oxide metabolism in the oral fluid are shown.

Comclusions. Based on the scientific data, it was concluded that dietary nitrate and bacteria of the oral cavity play a significant role in the synthesis of NO by enzymatic conversion. Regular intake of dietary nitrate-rich products is able to provide a systemic and local vasodilating effect through enterosalivary pathway and conversion of nitrite to nitric oxide.

 

References

Habermeyer, M., Roth, A., Guth, S., Diel, P., Engel, K. H., Ep, B., et al. (2015) Nitrate and nitrite in the diet: how to assess their benefit and risk for human health. Mol Nutr Food Res., 59(1), 106–128. doi: 10.1002/mnfr.201400286

Gassara, F., Kouassi, A. P., Brar, S. K., & Belkacemi, K. (2016) Green Alternatives to Nitrates and Nitrites in Meat-based Products-A( Review). Crit Rev Food Sci Nutr., 56(13), 2133–2148. doi: 10.1080/10408398.2013.812610

Chernikov, A. V., Bruskov, V. I., & Gudkov, S. V. (2013) Heat-induced formation of nitrogen oxides in water. Biol Phys., 39(4), 687–699. doi: 10.1007/s10867-013-9330-z

Hammes, W. P. (2012) Metabolism of nitrate in fermented meats: the characteristic feature of a specific group of fermented foods. Food Microbiol., 29(2), 151–156. doi: 10.1016/j.fm.2011.06.016

Etemadi, A., Sinha, R., Ward, M. H., Graubard, B., Inoue-Choi, M., Dawsey, S. M., & Abnet, C. C. (2017) Mortality from different causes associated with meat, heme iron, nitrates, and nitrites in the NIH-AARP Diet and Health Study: population based cohort study. BMJ., 357, j1957. doi: 10.1136/bmj.j1957

Inoue-Choi, M., Sinha, R., Gierach, G. L., & Ward, M. H. (2016) Red and processed meat, nitrite, and heme iron intakes and postmenopausal breast cancer risk in the NIH-AARP Diet and Health Study. Int J Cancer., 138(7), 1609–1618. doi: 10.1002/ijc.29901

Bylsma, L. C., & Alexander, D. D. (2015) A review and meta-analysis of prospective studies of red and processed meat, meat cooking methods, heme iron, heterocyclic amines and prostate cancer. Nutr J., 14, 125. doi: 10.1186/s12937-015-0111-3

Bedale, W., Sindelar, J. J., & Milkowski, A. L. (2016) Dietary nitrate and nitrite: Benefits, risks, and evolving perceptions. Meat Sci., 120, 85–92. doi: 10.1016/j.meatsci.2016.03.009

Hord, N. G. (2011) Dietary nitrates, nitrites, and cardiovascular disease. Curr Atheroscler Rep., 13(6), 484–492. doi: 10.1007/ s11883-011-0209-9

Koch, C. D., Gladwin, M. T., Freeman, B. A., Lundberg, J. O., Weitzberg, E., & Morris, A. (2017) Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health. Free Radic Biol Med., 105, 48–67. doi: 10.1016 /j.freeradbiomed. 2016.12.015

Bondonno, C. P., Liu, A. H., Croft, K. D., Ward, N. C., Puddey, I. B., Woodman, R. J., & Hodgson, J.M. (2015). Short-Term Effects of a High Nitrate Diet on Nitrate Metabolism in Healthy Individuals. Nutrients, 7(3), 1906–1915. doi: 10.3390/nu7031906

Jajja, A., Sutyarjoko, A., Lara, J., Rennie, K., Brandt, K., Qadir, O., & Siervo, M. (2014) Beetroot supplementation lowers daily systolic blood pressure in older, overweight subjects. Nutr Res., 34(10), 868–875. doi: 10.1016/j.nutres.2014.09.007

Mirmiran, M., Zadeh-Vakili, A., & Azizi, F. (2016) Consumption of nitrate-containing vegetables is inversely associated with hypertension in adults: a prospective investigation. Teh Lipid and Gluc Study J of Nephr., 29(3), 377–384. doi: 10.1007/s40620-015-0229-6

Shende, V., Biviji, A.T., & Akarte, N. (2013) Estimation and correlative study of salivary nitrate and nitrite in tobacco related oral squamous carcinoma and submucous fibrosis. J. Oral Maxillofac.Pathol., 17(3), 381–385. doi: 10.4103/0973-029X.125203

Takahashi, N. (2015) Oral microbiome metabolism: from “who are they?” to “what are they doing?” J. Dent Res. 94(12), 1628–1637. doi: 10.1177/0022034515606045

Lundberg, J. O., Weitzberg, E., & Gladwin, M. T. (2008) The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics. Nat Rev Drug Discov., 7(2), 156–167. doi: 10.1038/nrd2466

Doel, J., Benjamin, N., Hector, M., Rogers, M., & Allaker, R. (2005) Evaluation of bacterial nitrate reduction in the human oral cavity. Eur J of Oral Sci., 113, 14–19. doi: 10.1111/j.1600-0722.2004.00184.x

Hezel, M. P., & Weitzberg, E. (2015) The oral microbiome and nitric oxide homoeostasis. Oral Dis., 21(1), 7–16. doi: 10.1111/odi.12157

Hyde, E. R., Andrade, F., Vaksman, Z,.Parthasarathy, K., Jiang, H., Parthasarathy, D. K., et al. (2014) Metagenomic Analysis of Nitrate-Reducing Bacteria in the Oral Cavity: Implications for Nitric Oxide Homeostasis. PLoS One, 9(3), e88645. doi: 10.1371/journal.pone.0088645

Xia, D. S., Liu, Y., Zhang, C. M., Yang, S. H., & Wang, S. L. (2006) Antimicrobial effect of acidified nitrate and nitrite on six common oral pathogens in vitro. Chin Med J., 119(22), 1904–1919. doi: 10.1097/00029330-200611020-00010

Jiménez-López, C., & Lorenz, M. C. (2013) Fungal immune evasion in a model host–pathogen interaction: Candida albicans versus macrophages. PLoS Pathog., 9(11), e1003741. doi: 10.1371/journal.ppat.1003741

Mitsui, T., Fujihara, M., & Harasawa, R. (2013) Salivary nitrate and nitrite may have antimicrobial effects on Desulfovibrio species. Biosci Biotechnol Biochem., 77(12), 2489–2491. doi: 10.1271/bbb.130521

Koopman, J. E., Buijs, M. J., Brandt, B. W., Keijser, B. J., Crielaard, W., & Zaura, E. (2016) Nitrate and the Origin of Saliva Influence Composition and Short Chain Fatty Acid Production of Oral Microcosms. Microb Ecol. 72(2), 479–492. doi: 10.1007/s00248-016-0775-z

Sparacino-Watkins, C., Stolz, J. F., & Basu, P. (2014) Nitrate and Periplasmic Nitrate Reductases. Chem. Soc. Rev. 43(2), 676–706. doi: 10.1039/c3cs60249d

Lundberg, J. O., & Govoni, M. (2004) Inorganic nitrate is a possible source for systemic generation of nitric oxide. Free Radic. Biol. Med., 37(3), 395–400. doi: 10.1016/j.freeradbiomed.2004.04.027

Tiso, M., & Schechter, A. N. (2015) Nitrate Reduction to Nitrite, Nitric Oxide and Ammonia by Gut Bacteria under Physiological Conditions. PLoS One., 10(3), e0119712. doi: 10.1371/journal.pone.0119712

Liy, Y., Dan, J., Tao, H., & Xuedong, Z. (2008) Regulation of urease expression of Actinomyces naeslundii in biofilms in response to pH and carbohydrate. Oral Microb. Immun., 23(4), 315–9. doi: 10.1111/j.1399-302X.2008.00430.x

Kanady, J. A., Aruni, A. W., Ninnis, J. R., Hopper, A. O., Blood J. D., Byrd, B. L., et al. (2012) Nitrate reductase activity of bacteria in saliva of term and preterm infants. Nitric Oxide., 27(4), 193–200. doi: 10.1016/j.niox.2012.07.004

Schreiber, F., Stief, P., Gieseke, A., Heisterkamp, I. M., Verstraete, W., Beer, D., & Stoodley, P. (2010) Denitrification in human dental plaque. BMC Biol., 8, 24. doi: 10.1186/1741-7007-8-24

Lara, J., Ashor, A. W., Oggioni, C., Ahluwalia, A., Mathers, J. C., & Siervo, M. (2016) Effects of inorganic nitrate and beetroot supplementation on endothelial function: a systematic review and meta-analysis. Eur J Nutr., 55(2), 451–459. doi: 10.1007/s00394-015-0872-7

Pattillo, C. B, Bir, S., Rajaram, V., & Kevil, C. G. (2011) Inorganic nitrite and chronic tissue ischaemia: a novel therapeutic modality for peripheral vascular diseases. Cardiovasc Res., 89(3), 533–541. doi: 10.1093/ cvr/cvq 297

Kumar, D., Branch, B. G., Pattillo, C. B., Hood, J., Thoma, S., Simpson, S., et al. (2008) Chronic sodium nitrite therapy augments ischemia-induced angiogenesis and arteriogenesis. Proc Natl Acad Sci U S A., 105(21), 7540–7545. doi: 10.1073/pnas.0711480105

Jones, J. A., Hopper, A. O., Power, G. G., & Blood, A. B. (2015) Dietary intake and bio-activation of nitrite and nitrate in newborn infants. Pediatr Res., 77(1–2), 173–181. doi: 10.1038/pr.2014.168

Björne, H., Petersson, J., Phillipson, M., Weitzberg E., Holm, L., & Lundberg, J. O. (2004) Nitrite in saliva increases gastric mucosal blood flow and mucus thickness. Jour of Clin Investig., 113(1), 106–114. doi: 10.1172/JCI19019

Petersson, J., Carlström, M., Schreiber, O., Phillipson, M., Christoffersson, G., Jägare, A., et al. (2009) Gastroprotective and blood pressure lowering effects of dietary nitrate are abolished by an antiseptic mouthwash. Free Radic Biol Med., 46(8), 1068–1075. doi: 10.1016/j.freeradbiomed.2009.01.011

Petersson, J., Jädert, C., Phillipson, M., Bornique, S., Lundberg, J.O., & Holm, L. (2015) Physiological recycling of endogenous nitrate by oral bacteria regulates gastric mucus thickness. Free Radic Biol Med., 89, 241–247. doi: 10.1016/j.freeradbiomed. 2015.07.003

Song, P., Wu, L., & Guan, W. (2015) Dietary Nitrates, Nitrites, and Nitrosamines Intake and the Risk of Gastric Cancer: A Meta-Analysis. Nutrients., 7(12), 9872–95. doi: 10.3390/nu7125505

Pinheiro, L. C., Amaral, J. H., Ferreir, G. C., Portella, R. L., Ceron, C. S., & Montenegro, M. F. (2015) Gastric S-nitrosothiol formation drives the antihypertensive effects of oral sodium nitrite and nitrate in a rat model ofrenovascular hypertension. Free Radic Biol Med., 87, 252–62. doi: 10.1016/j.freeradbiomed.2015.06.038

Sukuroglu, E., Güncü, G. N., Kilinc, K., & Caglayan, F. (2015) Using Salivary Nitrite and Nitrate Levels as a Biomarker for Drug-Induced Gingival Overgrowth. Front Cell Infect Microbiol. 5, 87. doi: 10.3389/ fcimb.2015. 00087

Topcu, A. O., Akalin, F. A., Sahbazoglu, K. B., Yamalik, N., Kilinc, K., Karabulut, E., & Tözüm, T. F. (2014) Nitrite and nitrate levels of gingival crevicular fluid and saliva in subjects with gingivitis and chronic periodontitis. J Oral Maxillofac Res., 5(2), e5. doi: 10.5037/jomr.2014.5205

Poorsattar, B. A., Parsian, H., Khoram, M. A., Ghasemi, N., Bijani, A., & Khosravi-Samani, M. (2014) Diagnostic Role of Salivary and GCF Nitrite, Nitrate and Nitric Oxide to Distinguish Healthy Periodontium from Gingivitis and Periodontitis. Int J of Mol and Cel Med. 3(3), 138–145.

Hegde, M. N., Hegde, N. D., Ashok, A., & Shetty, S. (2012) Salivary nitric oxide (NO2+ NO3) as biomarker of dental caries in adults: an in vivo study. Int Res J of Pharm., 3(11), 100–102.

Enas, H. M., Dalaal, M. A. (2011) Saliva nitric oxide levels in relation to caries experience and oral hygiene. J of Adv Res. 2, 357–362.

Romanenko, Ye. G. (2013) Vliyanie vzaimodejstviya nespecificheskikh zashchitnykh faktorov rotovoj zhidkosti na sostoyanie tkanej parodonta u detej [The influence of the interaction of non-specific protective factors of oral fluid on the state of periodontal tissues in children]. Ukrainskyi stomatolohichnyi almanakh, 1, 96–99. [in Russian].

Saini, S., Noorani, H., & Shivaprakash, P. K. (2016) Correlation of plaque nitric oxide levels with plaque Streptococcus mutans, plaque pH and decayed, missing and filled teeth index of children of different age groups. J Indian Soc Pedod Prev Dent., 34(1), 17–24. doi: 10.4103/0970-4388.175505

Sundar, N. M., Krishnan, V., Krishnaraj, S., Hemalatha, V. T., & Alam, M. N. (2013) Comparison of the Salivary and the Serum Nitric Oxide Levels in Chronic and Aggressive Periodontitis. J Clin Diagn Res., 7(6), 1223–1227. doi: 10.7860/JCDR/2013/5386.3068

Downloads

How to Cite

1.
Romanenko YH, Hryhorenko LV, Komskyi MP, Sribnyk PL, Sinkovska OO. Nitric oxide formation in the metabolism of nitrates in the oral cavity. Zaporozhye Medical Journal [Internet]. 2019Oct.1 [cited 2024Jun.18];(5). Available from: http://zmj.zsmu.edu.ua/article/view/179472

Issue

Section

Review