title: Apples increase nitric oxide production by human saliva at the acidic pH of the stomach: a new biological function for polyphenols with a catechol group?
abstract: Dietary inorganic nitrate is secreted in saliva and reduced to nitrite by bacterial flora. At the acidic pH of the stomach nitrite is present as nitrous acid in equilibrium with nitric oxide (*NO), and other nitrogen oxides with nitrating and nitrosating activity. *NO in the stomach exerts several beneficial effects, but nitrosating/nitrating species have been implicated as a possible cause of epithelial neoplasia at the gastroesophageal junction. We investigated the effects of apple extracts on *NO release by human saliva at pH 2. A water extract obtained from apple homogenate increased *NO release caused by acidification of saliva. Data show that polyphenols were responsible for this activity, with chlorogenic acid and (+)-catechin the most active and concentrated species. However, ferulic acid, a hydroxycinnamic acid with only one aromatic hydroxyl group, did not increase *NO release. Fructose, the most representative sugar in apples, was also inactive. Interestingly, ascorbic acid in saliva induced a SCN(-)-enhanced burst of *NO but, unlike apple, the release was transient. The simultaneous addition of ascorbic acid and apple extract caused a burst of *NO followed by the increased steady-state level characteristic of saliva containing apple extract. Chlorogenic acid and (+)-catechin, but not ferulic acid, formed o-semiquinone radicals and nitrated polyphenols, suggesting the scavenging of *NO(2) by o-semiquinones. Our results propose that some apple polyphenols not only inhibit nitrosation/nitration but also promote *NO bio-availabilty at the gastric level, a previously unappreciated function.
authors.affiliation: Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Roma, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Peri
authors.forename: Donatella
authors.initials: D
authors.lastname: Pietraforte
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Scorza
authors.forename: Aurora
authors.initials: A
authors.lastname: Napolitano
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Fogliano
authors.forename: Maurizio
authors.initials: M
authors.lastname: Minetti
mesh_terms: D000975:Antioxidants / Q000737:chemistry; D001205:Ascorbic Acid / Q000737:chemistry; D002396:Catechols / Q000737:chemistry*; D003373:Coumaric Acids / Q000737:chemistry; D004563:Electrochemistry; D004578:Electron Spin Resonance Spectroscopy; D005419:Flavonoids / Q000737:chemistry*; D005609:Free Radicals; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D027845:Malus; D013058:Mass Spectrometry; D008956:Models, Chemical; D009566:Nitrates / Q000737:chemistry; D009569:Nitric Oxide / Q000737:chemistry / Q000378:metabolism*; D009573:Nitrites / Q000737:chemistry; D010636:Phenols / Q000737:chemistry*; D059808:Polyphenols; D012463:Saliva / Q000378:metabolism*; D013053:Spectrophotometry; D013696:Temperature; D013997:Time Factors; D015032:Zinc / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D002396:Catechols; D003373:Coumaric Acids; D005419:Flavonoids; D005609:Free Radicals; D009566:Nitrates; D009573:Nitrites; D010636:Phenols; D059808:Polyphenols; D009569:Nitric Oxide; C004999:ferulic acid; D015032:Zinc; D001205:Ascorbic Acid