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?

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)-N-center dot), and other nitrogen oxides with nitrating and nitrosating activity. (NO)-N-center dot 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)-N-center dot release by human saliva at pH 2. A water extract obtained from apple homogenate increased (NO)-N-center dot 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)-N-center dot release. Fructose, the most representative sugar in apples, was also inactive. Interestingly, ascorbic acid in saliva induced a SCN--enhanced burst of (NO)-N-center dot but, unlike apple, the release was transient. The simultaneous addition of ascorbic acid and apple extract caused a burst of (NO)-N-center dot 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 (NO2)-N-center dot by o-semiquitiones. Our results propose that some apple polyphenols not only inhibit nitrosation/nitration but also promote (NO)-N-center dot bioavailabilty at the gastric level, a previously unappreciated function. (c) 2005 Elsevier Inc. All rights reserved.