Therapeutic Interventions in Oral Submucous Fibrosis: An Experimental and Clinical Study

Abstract

Introduction Oral submucous fibrosis (OSF) is a chronic debilitating disease and premalignant condition of the oral cavity and is a serious public health issue in India and many parts of the world. The treatment is still elusive and empirical because of poorly understood etiopathogenesis, which is believed to be multifactorial including areca nut chewing, ingestion of chillies, genetic and immunologic processes, nutritional deficiencies, and many others. The present investigations was focused to understand the possible therapeutic interventions of anti-OSF agents in arecoline induced experimental in vitro model of OSF and clinical application of these anti-OSF agents in the restoration of various grade of the disease. Materials and Methods The 127 subjects were selected from patients who visited the OPD of Department of Oral and Maxillofacial Surgery, Faculty of Dental Sciences, K.G. Medical University, Lucknow. Further the subjects were divided in two groups on the basis of clinical examination. Group-1 subjects showed presence of fibrosis bands in the labial and/or buccal mucosa, loss of elasticity, difficulty to open the mouth and had a habit chewing arecanut in some form. Group-2 subjects had no habit of chewing areca-nut, were apparently healthy with no mucosal disorder. The samples were collected and were immediately transported to Indian Institute of Toxicology Research, Lucknow, for isolation and cultivation of primary cultures of mucosal fibroblast cells. Then isolation and cultivation of oral mucosal fibroblast, identification of non-cytotoxic doses of arecoline, real time PCR, immunocytochemistry, cytokine determination in culture cells, western blot analyses, functional activity of collagenase, lysyl oxidase enzyme activity, collagen beads assay, cyclooxygenase (COX-2) expression analysis was done. Results and Conclusions This study, shows that the reduction of phagocytic cells was strongly related to the arecoline levels in fibroblast culture when we exposed arecoline to normal oral mucosal cells (NOMC) and cells from OSF patient. An enhancement of phagocytic cells was observed following the pre exposure of cells to 1 lM dexamethasone, a glucocorticoids, In this study, histologic evidence is presented which supports the finding that COX-2 expression is upregulated in OSF specimens compared to normal oral submucosal cells. Strong immunostaining for COX-2 was detected in arecoline exposed NOMC and cells from OSF patient. Areca nut extract up-regulates prostaglandin production, cyclooxygenase-2 mRNA and protein expression of human oral keratinocytes. The number of phagocytic cells and phagocytic activity in cultured human oral fibroblasts from OSF site was lower than the fibroblasts from the normal regions of the same person.

Expression of cyclooxygenase 2 in oral submucous fibrosis: An immunohistochemical pilot study

“…COX (COX-2) expression analysis by Singh et al . [23] Immunocytochemistry and Western blot found synchronization in both the assays which support the finding that COX-2 expression is upregulated in OSF specimens compared to normal oral submucosal cells. Strong immunostaining for COX-2 was detected in arecoline exposed normal oral mucosal cells and in OSF samples.…”

A Comprehensive Analysis of the Role of Oxidative Stress in the Pathogenesis and Chemoprevention of Oral Submucous Fibrosis

“…Of the 51 laboratory-based studies and 1 dual study [8] included in this scoping review, 14 (26.9%) investigated the pathogenesis of OSMF, 13 (25%) demonstrated the significance of oxidative stress in the pathogenesis of OSMF, 7 (13.5%) investigated other biomarkers present in OSMF, 9 (17.3%) investigated antioxidant enzyme status in OSMF patients versus healthy controls, and ultimately 9 (17.3%) examined potential therapeutics for OSMF. Areca nut extracts (ANE) have been shown to have cytotoxic effects on hamster cheek pouch [3], normal mucosal cells [9,10], and gingival keratinocytes [11,12]. Consumption of BQ has been suggested to be associated with OSMF in oral epithelial cells [13,14], normal buccal mucosa fibroblasts (BMFs) [15], keratinocytes [16], gingival fibroblasts [17], Ha-CaT and HPL1D epithelial cell lines [18], and human umbilical vein endothelial cells [19].…”

Oral Submucous Fibrosis;

“…Oral submucous fibrosis is a complex, debilitating insidious and precancerous disease of the oral cavity. 1 The identifying characteristics of oral submucous fibrosis is presence of fibrous bands in cheeks, lips and palate due to underlying submucosal fibrosis that initiates in the oral cavity and progresses to the oropharynx and upper third of the esophagus. It is always associated with juxta epithelial inflammation and progressive fibrosis of the lamina propria.…”

“…Various therapeutic interventions have been proposed that work against the different mechanisms of pathogenesis of OSF. 1 There has been considerable work in finding diagnostic and prognostic salivary biomarkers for early minimally invasive detection of Oral Submucous fibrosis in high risk patients. Advances in salivary proteomics and metabolomics has indicated significantly lower expression levels of MMP-2, MMP-9 and salivary Statherin in saliva of patients with Oral Submucous Fibrosis and have potential for early detection of malignant change in OSF.…”