{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T04:31:42Z","timestamp":1770438702359,"version":"3.49.0"},"reference-count":45,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2014,4,25]],"date-time":"2014-04-25T00:00:00Z","timestamp":1398384000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Australian Dental Research Fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Oral Pathology Medicine"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Oral submucous fibrosis is a pre\u2010malignant fibrotic condition caused by areca nut use and involves reduced mucosal vascularity. Arecoline is the principal areca nut alkaloid and is cytotoxic for epithelium and fibroblasts. Endothelial cell cycle arrest is reported on exposure to arecoline, as is cytotoxicity for endothelial\u2013lung carcinoma hybrid cells. We here describe cytotoxicity for primary human endothelial cultures from seven separate donors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>Human umbilical vein endothelial cells were exposed to increasing concentrations of arecoline and examined by: phase\u2010contrast microscopy, haemocytometer counts, transmission electron microscopy, lactate dehydrogenase release and the methyl\u2010thiazol\u2010tetrazolium assay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Vacuolation and detachment of endothelium were observed at and above arecoline concentrations of 333\u00a0\u03bcg\/ml or more. Ultrastructural features of cellular stress were seen after 24\u2010h treatment with 111\u00a0\u03bcg\/ml arecoline and included reduced ribosomal studding of endoplasmic reticulum, increased autophagolysosomal structures, increased vacuolation and reduced mitochondrial cristae with slight swelling. Similar changes were seen at 4\u00a0h with arecoline at 333\u00a0\u03bcg\/ml or above, but with more severe mitochondrial changes including increased electron density of mitochondrial matrix and greater cristal swelling, while by 24\u00a0h, these cells were frankly necrotic. Haemocytometer counts were paralleled by both lactate dehydrogenase release and the methyl\u2010thiazol\u2010tetrazolium assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Arecoline is cytotoxic via necrosis for endothelium, while biochemical assays indicate no appreciable cellular leakage before death and detachment, as well as no clear effect on mitochondrial function in viable cells. Arecoline toxicity may thus contribute to reduced vascularity in oral submucous fibrosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jop.12186","type":"journal-article","created":{"date-parts":[[2014,4,25]],"date-time":"2014-04-25T04:52:52Z","timestamp":1398401572000},"page":"761-769","source":"Crossref","is-referenced-by-count":26,"title":["Arecoline is cytotoxic for human endothelial cells"],"prefix":"10.1111","volume":"43","author":[{"given":"Mafaz","family":"Ullah","sequence":"first","affiliation":[{"name":"Cellular and Molecular Pathology Research Unit Department of Oral Pathology and Oral Medicine Westmead Centre for Oral Health Westmead Hospital The University of Sydney Westmead NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen","family":"Cox","sequence":"additional","affiliation":[{"name":"Department of Oral Surgery Westmead Centre for Oral Health Westmead Hospital The University of Sydney Westmead NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Kelly","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Pathology Research Unit Department of Oral Pathology and Oral Medicine Westmead Centre for Oral Health Westmead Hospital The University of Sydney Westmead NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ross","family":"Boadle","sequence":"additional","affiliation":[{"name":"Westmead Millennium Institute and Electron Microscope Laboratory ICPMR Westmead Hospital Westmead NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans","family":"Zoellner","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Pathology Research Unit Department of Oral Pathology and Oral Medicine Westmead Centre for Oral Health Westmead Hospital The University of Sydney Westmead NSW Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,4,25]]},"reference":[{"key":"e_1_2_5_2_1","first-page":"603","article-title":"Oral submucous fibrosis: a review","volume":"18","author":"Pindborg JJ","year":"1989","journal-title":"Ann Acad Med Singapore"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0528.1987.tb00526.x"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.2008.00696.x"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2005.08.005"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M404465200"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.1999.tb01998.x"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9969(86)90112-3"},{"key":"e_1_2_5_9_1","first-page":"161","article-title":"Cytotoxic and cytostatic effects of arecoline on oral mucosal fibroblasts","volume":"21","author":"Tsai CL","year":"1997","journal-title":"Proc Natl Sci Counc Repub China B"},{"key":"e_1_2_5_10_1","first-page":"3","article-title":"Submucous fibrosis in non\u2010betel nut chewing subjects","volume":"16","author":"Seedat HA","year":"1988","journal-title":"J de Biologie Buccale"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1368-8375(01)00003-3"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/13556210120091482"},{"key":"e_1_2_5_13_1","first-page":"281","article-title":"Areca\u2010nut toxicity in cultured human buccal epithelial cells","volume":"1991","author":"Sundqvist K","year":"1991","journal-title":"IARC Sci Publ"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.1998.tb02096.x"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.2009.00881.x"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/6.2.295"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.1989.tb01562.x"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1159\/000101777"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0714.1991.tb00434.x"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1699-0463.1967.tb01280.x"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.4103\/0970-9290.90287"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1515\/JPM.2005.072"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00784-011-0604-1"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(83)90438-6"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01404408"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.3109\/10623329609024694"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1159\/000087213"},{"key":"e_1_2_5_28_1","unstructured":"KumarV AbbasAK AsterJC.Robbins basic pathology. 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