4.5 Article

Nicotine is an independent potential fibrogenic mediator in non-betel quid associated oral submucous fibrosis

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MEDICAL HYPOTHESES
卷 165, 期 -, 页码 -

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ELSEVIER
DOI: 10.1016/j.mehy.2022.110891

关键词

Oral cancer; Oral submucous fibrosis; Nicotine; Nitrosamines; Arecoline; Alkaline pH

资金

  1. Wellcome Trust/DBT India Alliance [IA/CPHI/18/1/503927]

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Oral submucous fibrosis is an irreversible, progressive, potentially malignant condition that develops among habitual areca nut chewers. The active ingredient, nicotine, in tobacco is addictive, and the chronic use of chewing tobacco increases the risk of mouth cancer.
Oral submucous fibrosis (OSF) is an irreversible, progressive, potentially malignant condition that develops among habitual areca nut chewers. The role of nicotine due to chewing or smoking tobacco as an independent risk factor for OSF is yet to be fully established. However, the active ingredient, nicotine, in tobacco is addictive, and the chronic use of chewing tobacco increases the risk of mouth cancer. The hypothesis that nicotine promotes fibrosis is based on a customized literature search unraveling the novel pathways and mechanisms of nicotineinduced oral fibrogenesis. Chronic exposure to nicotine has been shown to induce fibrosis in normal rats through ??7-nAChR. Nicotine and derived nitrosamines act through nAChR on epithelial cells to upregulate proinflammatory cytokines IL-1??, TNF-??, and profibrotic factor TGF-??1. Nicotine promotes fibrosis by the nAchR/ AKT/YAP-TEAD/BIP pathway, which promotes EMT and the generation of myofibroblasts. Additionally, nicotine damages the endothelial cells to promote vascular rarefaction and fibrosis. Since profibrogenic nicotine is better absorbed at alkaline pH, chewed tobacco products are made alkaline to increase their addictive power. Nicotine may thus enhance collagen accumulation and ensuing fibrosis in impending OSF. This hypothesis explains the sporadic reports of OSF among individuals who chew tobacco and/or smoke without the habit of chewing areca nut habit.

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