Oral submucous fibrosis (OSMF) is a chronic oral potentially malignant disorder (OPMD). It is described as a scarring disease of the oral mucosa associated with excess oxidants and insufficient antioxidants. While it is becoming increasingly accepted that oxidative stress results in excessive accumulation of collagen and progressive fibrosis of the submucosal tissues, there is limited data regarding the moderation of oxidative stress to initiate or prevent OSMF. To assess the scope for mechanism-based approaches to prevent or reverse OSMF, we systematically evaluated the existing literature and investigated the role of oxidative stress in the pathogenesis and chemoprevention of OSMF. A search for relevant articles on PubMed and Scopus was undertaken using pre-defined inclusion and exclusion criteria. A total of 78 articles were selected in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. The articles eligible for assessment investigated both OSMF and/or oxidative stress biomarkers or specific antioxidants. Both in vitro and human studies consistently demonstrated variations in oxidative stress biomarker levels in OSMF and revealed an increase in oxidative stress, paralleling the development of the disease. Furthermore, the use of antioxidant supplements was overall associated with an improvement in clinical outcomes. Having identified the significance of oxidative stress in OSMF and the therapeutic potential of antioxidant supplements, this scoping review highlights the need for further well-designed studies in the development of mechanism-based interventions for managing OSMF.

The addition of betel inflorescence (BI) and slaked lime (calcium hydroxide) to betel quid (BQ) formulation may be detrimental to human health. Here, we assessed BI extracts prepared using artificial saliva or aqueous solution with or without adding slaked lime to mimic the release of phytochemicals from BI in the oral cavity. The extracts were also profiled by HPLC-DAD-ESI-QTOF-MS/MS to understand the quality and quantity of phytochemicals released. The results indicate that slaked lime facilitates the extraction of phenolics, likely due to a high pH. In a simulated oral environment with artificial saliva, the addition of slaked lime promotes the release of safrole, a well-known carcinogen. Dominant phytochemicals detected also include eugenol, acetyl eugenol and methyl eugenol, and only a fraction of these compounds is released in the simulated oral environment. This study reveals that environmental conditions can considerably affect the extraction of phytochemicals and triggers further investigation on how chewing practices may influence the release and activity of carcinogens.