{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T19:58:34Z","timestamp":1770494314361,"version":"3.49.0"},"reference-count":54,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,4,13]],"date-time":"2024-04-13T00:00:00Z","timestamp":1712966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"intramural NIDDK\/NIH","doi-asserted-by":"publisher","award":["ZIA DK 025104-15"],"award-info":[{"award-number":["ZIA DK 025104-15"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Nitrate (NO3\u2212) obtained from the diet is converted to nitrite (NO2\u2212) and subsequently to nitric oxide (NO) within the body. Previously, we showed that porcine eye components contain substantial amounts of nitrate and nitrite that are similar to those in blood. Notably, cornea and sclera exhibited the capability to reduce nitrate to nitrite. To gain deeper insights into nitrate metabolism in porcine eyes, our current study involved feeding pigs either NaCl or Na15NO3 and assessing the levels of total and 15N-labeled NO3\u2212\/NO2\u2212 in various ocular tissues. Three hours after Na15NO3 ingestion, a marked increase in 15NO3\u2212 and 15NO2\u2212 was observed in all parts of the eye; in particular, the aqueous and vitreous humor showed a high 15NO3\u2212 enrichment (77.5 and 74.5%, respectively), similar to that of plasma (77.1%) and showed an even higher 15NO2\u2212 enrichment (39.9 and 35.3%, respectively) than that of plasma (19.8%). The total amounts of NO3\u2212 and NO2\u2212 exhibited patterns consistent with those observed in 15N analysis. Next, to investigate whether nitrate or nitrite accumulate proportionally after multiple nitrate treatments, we measured nitrate and nitrite contents after supplementing pigs with Na15NO3 for five consecutive days. In both 15N-labeled and total nitrate and nitrite analysis, we did not observe further accumulation of these ions after multiple treatments, compared to a single treatment. These findings suggest that dietary nitrate supplementation exerts a significant influence on nitrate and nitrite levels and potentially NO levels in the eye and opens up the possibility for the therapeutic use of dietary nitrate\/nitrite to enhance or restore NO levels in ocular tissues.<\/jats:p>","DOI":"10.3390\/nu16081154","type":"journal-article","created":{"date-parts":[[2024,4,15]],"date-time":"2024-04-15T03:56:13Z","timestamp":1713153373000},"page":"1154","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dietary Nitrate Metabolism in Porcine Ocular Tissues Determined Using 15N-Labeled Sodium Nitrate Supplementation"],"prefix":"10.3390","volume":"16","author":[{"given":"Ji Won","family":"Park","sequence":"first","affiliation":[{"name":"Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA"},{"name":"Molecular Medicine Branch, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbora","family":"Piknova","sequence":"additional","affiliation":[{"name":"Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA"},{"name":"Molecular Medicine Branch, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5942-4164","authenticated-orcid":false,"given":"Khalid J.","family":"Tunau-Spencer","sequence":"additional","affiliation":[{"name":"Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA"},{"name":"Molecular Medicine Branch, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha M.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA"},{"name":"Molecular Medicine Branch, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongyi","family":"Cai","sequence":"additional","affiliation":[{"name":"Clinical Mass Spectrometry Core, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA"},{"name":"Clinical Mass Spectrometry Core, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8571-398X","authenticated-orcid":false,"given":"Peter J.","family":"Walter","sequence":"additional","affiliation":[{"name":"Clinical Mass Spectrometry Core, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA"},{"name":"Clinical Mass Spectrometry Core, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Audrey","family":"Jenkins","sequence":"additional","affiliation":[{"name":"MedStar Health Research Institute, Washington, DC 20010, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Hellinga","sequence":"additional","affiliation":[{"name":"MedStar Health Research Institute, Washington, DC 20010, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leonard M.","family":"Parver","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Medstar Georgetown University Hospital, Washington, DC 20007, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan N.","family":"Schechter","sequence":"additional","affiliation":[{"name":"Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA"},{"name":"Molecular Medicine Branch, National Institutes of Health, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1111\/bph.14484","article-title":"Nitrite and nitrate chemical biology and signalling","volume":"176","author":"DeMartino","year":"2019","journal-title":"Br. 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