Like SLT, areca nut has been classified as a Group 1 human carcinogen (IARC, 2004).[] The major constituents of areca nut are carbohydrates, fats, proteins, crude fiber, polyphenols, alkaloids such as arecoline, arecaidine, guvacine, guvacoline,[] and minerals.[] Presence of sodium, magnesium, chlorine, calcium, vanadium, manganese, bromine, and copper has been reported in areca nut, pan masala, and other areca nut-containing chewing products.[] Arecoline, the major alkaloid in areca nut, has been found to stimulate collagen synthesis in fibroblasts;[] whereas, catechin, flavonoid, and tannin compounds in areca nut cross-linked collagen fibers making them less susceptible to collagenase degradation.[] It has also been suggested that copper upregulates lysyl oxidase, leading to excessive cross-linking and accumulation of collagen in patients with oral submucous fibrosis (OSF).[] In a study of seven Indian SLT products, high level of copper were detected in four gutka products as compared to zarda , creamy snuff, and khaini , which do not contain areca nut.[] Jacob et al .,[] demonstrated a definitive dose-dependent relationship between the frequency and duration of chewing areca nut without tobacco and the development of OSF in users

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