{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T14:25:20Z","timestamp":1790087120392,"version":"4.0.1"},"reference-count":42,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2009,4,1]],"date-time":"2009-04-01T00:00:00Z","timestamp":1238544000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Periodontal Research"],"published-print":{"date-parts":[[2009,10]]},"abstract":"<jats:p><jats:bold>Background and Objective:\u2002<\/jats:bold> Arecoline, an arecanut alkaloid present in the saliva of betel quid chewers, has been implicated in the pathogenesis of a variety of inflammatory oral diseases, including oral submucous fibrosis and periodontitis. To understand the molecular basis of arecoline action in epithelial changes associated with these diseases, we investigated the effects of arecoline on human keratinocytes with respect to cell growth regulation and the expression of stress\u2010responsive genes.<\/jats:p><jats:p><jats:bold>Material and Methods:\u2002<\/jats:bold> Human keratinocyte cells (of the HaCaT cell line) were treated with arecoline, following which cell viability was assessed using the Trypan Blue dye\u2010exclusion assay, cell growth and proliferation were analyzed using the MTT (3\u2010[4,5\u2010dimethylthiazol\u20102\u2010yl]\u20102,5\u2010diphenyltetrazolium bromide) and 5\u2010bromo\u20102\u2010deoxyuridine incorporation assays, cell cycle arrest and generation of reactive oxygen species were examined using flow cytometry, and gene expression changes were investigated using the reverse transcription\u2013polymerase chain reaction technique. The role of oxidative stress, muscarinic acetylcholine receptor and mitogen\u2010activated protein kinase (MAPK) pathways were studied using specific inhibitors. Western blot analysis was performed to study p38 MAPK activation.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> Arecoline induced the generation of reactive oxygen species and cell cycle arrest at the G1\/G0 phase in HaCaT cells without affecting the expression of p21\/Cip1. Arecoline\u2010induced epithelial cell death at higher concentrations was caused by oxidative trauma without eliciting apoptosis. Sublethal concentrations of arecoline upregulated the expression of the following stress\u2010responsive genes: heme oxygenase\u20101; ferritin light chain; glucose\u20106\u2010phosphate dehydrogenase; glutamate\u2010cysteine ligase catalytic subunit; and glutathione reductase. Additionally, there was a dose\u2010dependent induction of interleukin\u20101alfa mRNA by arecoline via oxidative stress and p38 MAPK activation.<\/jats:p><jats:p><jats:bold>Conclusion:\u2002<\/jats:bold> Our data highlight the role of oxidative stress in arecoline\u2010mediated cell death, gene regulation and inflammatory processes in human keratinocytes.<\/jats:p>","DOI":"10.1111\/j.1600-0765.2008.01176.x","type":"journal-article","created":{"date-parts":[[2009,4,2]],"date-time":"2009-04-02T03:39:17Z","timestamp":1238643557000},"page":"673-682","source":"Crossref","is-referenced-by-count":61,"title":["Regulation of oxidative\u2010stress responsive genes by arecoline in human keratinocytes"],"prefix":"10.1111","volume":"44","author":[{"given":"G. 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