{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T05:16:48Z","timestamp":1783055808555,"version":"3.54.6"},"reference-count":75,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:00:00Z","timestamp":1782777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004357","name":"Procter & Gamble Company","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100004357","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This research examined host metabolic processes associated with gingivitis and potential impacts of interventions. First, gingival brush samples from a previously reported clinical study in which participants used an intervention (stannous fluoride (SnF2) toothpaste\/cetylpyridinium chloride rinse\/oscillating-rotating electric toothbrush) or control (standard fluoride toothpaste\/manual toothbrush) were analyzed with Metabolon metabolomic assessment. Next, hypotheses were generated about mechanisms of metabolic observations and tested in two in vitro models. Human primary blood cells were treated with endotoxins and outer membrane vesicles (OMVs) in the presence of SnF2. In clinical brush samples, 46 metabolites decreased with intervention at Week 3, including 9- and 13-hydroxyoctadecadienoic acid, citrulline, adenine, and hypoxanthine. Seven metabolites related to nitrogen metabolism and citrulline production were selected for targeted quantification. They were low in health and increased in gingivitis. Targeted quantification demonstrated reduced citrulline, succinate, ornithine and deoxycarnitine (p \u2264 0.001 for all) between baseline and Week 6 with intervention; reductions were greater for intervention vs. control for citrulline, succinate and deoxycarnitine at Week 6 (p \u2264 0.019). In vitro, endotoxin and OMVs increased citrulline and nitric oxide (NO). SnF2 inhibited elevation of both. Citrulline, deoxycarnitine, succinate, and ornithine were identified as potential novel markers of gingivitis. Elevated NO production is a potential driver of oxidative stress, reduced with intervention.<\/jats:p>","DOI":"10.3390\/ijms27135882","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T08:26:15Z","timestamp":1782807975000},"page":"5882","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Oral Care Intervention on Gingivitis-Mediated Induction of Nitric Oxide Synthesis and Oxidative Stress"],"prefix":"10.3390","volume":"27","author":[{"given":"Malgorzata","family":"Klukowska","sequence":"first","affiliation":[{"name":"Global Oral Care R&D, The Procter & Gamble Company, Mason Business and Innovation Center, 8700 Mason-Montgomery Road, Mason, OH 45040, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8266-0455","authenticated-orcid":false,"given":"Sancai","family":"Xie","sequence":"additional","affiliation":[{"name":"Corporate Functions R&D, The Procter & Gamble Company, Mason, OH 45040, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9512-5441","authenticated-orcid":false,"given":"Lijuan","family":"Li","sequence":"additional","affiliation":[{"name":"Corporate Functions R&D, The Procter & Gamble Company, Mason, OH 45040, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5311-8860","authenticated-orcid":false,"given":"Tom","family":"Huggins","sequence":"additional","affiliation":[{"name":"Corporate Functions R&D, The Procter & Gamble Company, Mason, OH 45040, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Ashe","sequence":"additional","affiliation":[{"name":"Corporate Functions R&D, The Procter & Gamble Company, Mason, OH 45040, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chelsea","family":"Tan","sequence":"additional","affiliation":[{"name":"Biosciences, Procter & Gamble International Operations SA, P&G Singapore Innovation Center, 70 Biopolis St., Singapore 138547, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Circello","sequence":"additional","affiliation":[{"name":"Corporate Functions R&D, The Procter & Gamble Company, Mason, OH 45040, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6908-0948","authenticated-orcid":false,"given":"Xingtao","family":"Wei","sequence":"additional","affiliation":[{"name":"Corporate Functions R&D, The Procter & Gamble Company, Mason, OH 45040, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niranjan","family":"Ramji","sequence":"additional","affiliation":[{"name":"Global Oral Care R&D, The Procter & Gamble Company, Mason Business and Innovation Center, 8700 Mason-Montgomery Road, Mason, OH 45040, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald J.","family":"White","sequence":"additional","affiliation":[{"name":"Global Oral Care R&D, The Procter & Gamble Company, Mason Business and Innovation Center, 8700 Mason-Montgomery Road, Mason, OH 45040, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron R.","family":"Biesbrock","sequence":"additional","affiliation":[{"name":"Global Oral Care R&D, The Procter & Gamble Company, Mason Business and Innovation Center, 8700 Mason-Montgomery Road, Mason, OH 45040, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1111\/j.1600-051X.1986.tb01473.x","article-title":"Epidemiology of gingivitis","volume":"13","author":"Stamm","year":"1986","journal-title":"J. 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