Salivary nitrate/nitrite and acetaldehyde in humans: potential combination effects in the upper gastrointestinal tract and possible consequences for the in vivo formation of N-nitroso compounds-a hypothesis.

Henry Jäger, Pablo Steinberg, Wim Wätjen, Stefan Vieths, Richard Stadler, Joachim Spranger, Angelika Roth, Elke Röhrdanz, Ute Nöthlings, Doris Marko, Angela Mally, Marcel Leist, Alfonso Lampen, Dirk W Lachenmeier, Sabine Kulling, Hans-Georg Joost, Gerhard Eisenbrand, Hans-Ulrich Humpf, Thomas Henle, Jan G Hengstler, Michael Hellwig, Volker Heinz, Dirk Haller, Sabine Guth, Tilman Grune, Bernd Epe, Barbara Engeli, Karl-Heinz Engel, Patrick Diel, Alexander T Cartus, Matthias Baum

Journal: Archives of toxicology 2022;96(6):1905-1914

PMID: 35504979

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Abstract

Subsequent to the dietary uptake of nitrate/nitrite in combination with acetaldehyde/ethanol, combination effects resulting from the sustained endogenous exposure to nitrite and acetaldehyde may be expected. This may imply locoregional effects in the upper gastrointestinal tract as well as systemic effects, such as a potential influence on endogenous formation of N-nitroso compounds (NOC). Salivary concentrations of the individual components nitrate and nitrite and acetaldehyde are known to rise after ingestion, absorption and systemic distribution, thereby reflecting their respective plasma kinetics and parallel secretion through the salivary glands as well as the microbial/enzymatic metabolism in the oral cavity. Salivary excretion may also occur with certain drug molecules and food constituents and their metabolites. Therefore, putative combination effects in the oral cavity and the upper digestive tract may occur, but this has remained largely unexplored up to now. In this Guest Editorial, published evidence on exposure levels and biokinetics of nitrate/nitrite/NO, NOC and acetaldehyde in the organism is reviewed and knowledge gaps concerning combination effects are identified. Research is suggested to be initiated to study the related unresolved issues.

Address: , Kühler Grund 48/1, 69126, Heidelberg, Germany. [email protected].; Solenis Germany Industries GmbH, Fütingsweg 20, 47805, Krefeld, Germany.; Chemservice S.A., 13, Fausermillen, 6689, Mertert, Luxembourg.; Department of Molecular and Cellular Sports Medicine, Institute of Cardiovascular Research and Sports Medicine, German Sport University Cologne, Am Sportpark Müngersdorf 6, 50933, Cologne, Germany.; Chair of General Food Technology, Technical University of Munich, Maximus-von-Imhof-Forum 2, 85354, Freising, Germany.; Risk Assessment Division, Federal Food Safety and Veterinary Office (FSVO), Schwarzenburgstrasse 155, 3003, Bern, Switzerland.; Institute of Pharmaceutical and Biomedical Sciences, University of Mainz, Staudinger Weg 5, 55128, Mainz, Germany.; Department of Molecular Toxicology, German Institute of Human Nutrition (DIfE), Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany.; Leibniz Research Centre for Working Environment and Human Factors (IfADo), Ardeystr. 67, 44139, Dortmund, Germany.; ZIEL, Institute for Food and Health, Technical University of Munich, 85354, Freising, Germany.; Chair of Nutrition and Immunology, Technical University of Munich, Gregor-Mendel-Str. 2, 85354, Freising, Germany.; German Institute of Food Technologies (DIL), Prof.-von-Klitzing-Str. 7, 49610, Quakenbrück, Germany.; Institute of Food Chemistry, Technical University of Braunschweig, Schleinitzstr. 20, 38106, Braunschweig, Germany.; Department of Food Chemistry, TU Dresden, Bergstrasse 66, 01069, Dresden, Germany.; Institute of Food Chemistry, Westfälische Wilhelms-Universität Münster, Corrensstraße 45, 48149, Münster, Germany.; Institute of Food Technology, University of Natural Resources and Life Sciences (BOKU), Muthgasse 18, 1190, Vienna, Austria.; Department of Experimental Diabetology, German Institute of Human Nutrition (DIfE), Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany.; Department of Safety and Quality of Fruit and Vegetables, Federal Research Institute of Nutrition and Food, Max Rubner-Institut, Haid-und-Neu-Straße 9, 76131, Karlsruhe, Germany.; Chemisches und Veterinäruntersuchungsamt Karlsruhe, Weißenburger Straße 3, 76187, Karlsruhe, Germany.; Risk Assessment Strategies, Bundesinstitut für Risikobewertung (BfR), Max-Dohrn-Straße 8-10, Berlin, Germany.; In Vitro Toxicology and Biomedicine, Department Inaugurated by the Doerenkamp-Zbinden Foundation, University of Konstanz, Box 657, 78457, Konstanz, Germany.; Department of Toxicology, University of Würzburg, Versbacher Str. 9, 97078, Würzburg, Germany.; Department of Food Chemistry and Toxicology, Faculty of Chemistry, University of Vienna, Währinger Straße 38, 1090, Vienna, Austria.; Department of Nutrition and Food Sciences, Nutritional Epidemiology, Rheinische Friedrich-Wilhelms University Bonn, Friedrich-Hirzebruch-Allee 7, 53115, Bonn, Germany.; Unit Reproductive and Genetic Toxicology, Federal Institute for Drugs and Medical Devices (BfArM), Kurt-Georg-Kiesinger Allee 3, 53175, Bonn, Germany.; Department of Endocrinology and Metabolic Medicine, Campus Benjamin Franklin, Charité University Medicine, Hindenburgdamm 30, 12203, Berlin, Germany.; Institute of Food Safety and Analytic Sciences, Nestlé Research Centre, Route du Jorat 57, 1000, Lausanne 26, Switzerland.; Federal Institute for Vaccines and Biomedicines, Paul-Ehrlich-Institut, Paul-Ehrlich-Straße 51-59, 63225, Langen, Germany.; Institut für Agrar- und Ernährungswissenschaften, Martin-Luther-Universität Halle-Wittenberg, Weinbergweg 22, 06120, Halle (Saale), Germany.; Federal Research Institute of Nutrition and Food, Max Rubner-Institut, Haid-und-Neu-Straße 9, 76131, Karlsruhe, Germany. [email protected].

DOI: 10.1007/s00204-022-03296-0

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MeSH Terms: Acetaldehyde, Humans, Nitrates, Nitrites, Nitroso Compounds, Saliva, Upper Gastrointestinal Tract