{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T03:00:11Z","timestamp":1790650811474,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The increasing therapeutic incorporation of cannabis has expanded phytocannabinoid application, yet peripheral adverse effects like xerostomia raise concerns regarding emerging biotechnological formulations. This study evaluated the effects of cannabis\u2010based lipid nanoemulsions on the rat submandibular gland parenchyma. Forty male Wistar rats were distributed into five daily oral treatment groups for 21\u2009days: vehicle control, CBD and THC (2.5 and 5\u2009mg\/kg), and isolated CBD (2.5 and 5\u2009mg\/kg). Submandibular glands were assessed via histopathology (H&amp;E), acinar histomorphometry, periodic acid\u2010Schiff (PAS) histochemistry, immunohistochemistry for 8\u2010hydroxy\u20102\u2032\u2010deoxyguanosine (8\u2010OHdG), cleaved caspase\u20103, and cyclooxygenase\u20102 (COX\u20102) and collagen birefringence under polarized light. All treated groups exhibited significant histopathological alterations versus control (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). Isolated CBD groups displayed the most pronounced tissue injury, with extensive cytoplasmic vacuolization, hemorrhage, and severe acinar disorganization, although acinar density remained comparable among groups. PAS reactivity was significantly reduced only in CBD and THC groups, whereas oxidative DNA damage (8\u2010OHdG) was significantly increased in the CBD 2.5\u2010mg\/kg group. All treated groups demonstrated enhanced periductal collagen deposition: isolated CBD groups showed a predominance of mature type I collagen fibers, whereas CBD and THC 5\u2009mg\/kg exhibited a higher proportion of immature type III fibers, indicating distinct extracellular matrix remodeling patterns. In conclusion, cannabis\u2010based lipid nanoemulsions induced histopathological injury, oxidative stress, and extracellular matrix remodeling in rat submandibular glands. Notably, isolated CBD produced more severe glandular damage than the CBD and THC combination, suggesting a protective modulatory effect of THC against CBD\u2010induced toxicity in salivary tissue, consistent with a pharmacodynamic interaction between these phytocannabinoids.\n                  <\/jats:p>","DOI":"10.1002\/jat.70454","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T02:46:23Z","timestamp":1790649983000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Subchronic Exposure to Cannabis\u2010Based Nanoemulsions Induces Histopathological and Molecular Alterations in the Rat Submandibular Gland"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-2386-2126","authenticated-orcid":false,"given":"Lorrany Avanci","family":"Bullo","sequence":"first","affiliation":[{"name":"Department of Biosciences, Institute of Health and Society Federal University of Sao Paulo UNIFESP  Santos SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5951-4399","authenticated-orcid":false,"given":"Gabriel Carvalhal","family":"de Aguiar","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Institute of Health and Society Federal University of Sao Paulo UNIFESP  Santos SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0999-5847","authenticated-orcid":false,"given":"Daniel Vitor","family":"Souza","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Institute of Health and Society Federal University of Sao Paulo UNIFESP  Santos SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"dos Anjos Ros\u00e1rio","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Institute of Health and Society Federal University of Sao Paulo UNIFESP  Santos SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4408-1503","authenticated-orcid":false,"given":"Flavia","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Institute of Health and Society Federal University of Sao Paulo UNIFESP  Santos SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando Augusto Cintra","family":"Magalhaes","sequence":"additional","affiliation":[{"name":"Department of Biosciences, Institute of Health and Society Federal University of Sao Paulo UNIFESP  Santos SP Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1849-5403","authenticated-orcid":false,"given":"N\u00e1gila Maria Pontes Silva","family":"Ricardo","sequence":"additional","affiliation":[{"name":"Department of Organic and Inorganic Chemistry Federal University of Cear\u00e1  Fortaleza CE 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