Evaluation of transforming growth factor beta1 gene in oral submucous fibrosis induced in Sprague-Dawley rats by injections of areca nut and pan masala (commercial areca nut product) extracts

Maria, Shilpa; Kamath, Venkatesh V; Satelur, Krishnanand; Rajkumar, Komali

doi:10.4103/0973-1482.148729

Cited by 18 publications

(6 citation statements)

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“…The ANE-induced OSF in rats is mimicking the human pathogenesis, where most of the disease markers and oxidative stress were elevated. The main markers such as mouth opening test and body weight changes were almost similar to human OSF (Maria et al 2016 ; Shekatkar et al 2022 ). EGCG hydrogel showed an improvement in the antioxidant level compared to the OSF-induced rats, which was due to the ability of the EGCG hydrogel to suppress the oxidants or free radicals present and improve the antioxidant activity.…”

Section: Discussionmentioning

confidence: 90%

Polyphenol-based targeted therapy for oral submucous fibrosis

Mehta¹,

Paliwal²,

Muttigi³

et al. 2023

Inflammopharmacol

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Oral submucous fibrosis (OSF) is a chronic, progressive, and precancerous condition mainly caused by chewing areca nut. Currently, OSF therapy includes intralesional injection of corticosteroids with limited therapeutic success in disease management. Therefore, a combined approach of in silico, in vitro and in vivo drug development can be helpful. Polyphenols are relatively safer than other synthetic counterparts. We used selected polyphenols to shortlist the most suitable compound by in silico tools. Based on the in silico results, epigallocatechin-3-gallate (EGCG), quercetin (QUR), resveratrol, and curcumin had higher affinity and stability with the selected protein targets, transforming growth factor beta-1 (TGF-β1), and lysyl oxidase (LOX). The efficacy of selected polyphenols was studied in primary buccal mucosal fibroblasts followed by in vivo areca nut extract induced rat OSF model. In in vitro studies, the induced fibroblast cells were treated with EGCG and QUR. EGCG was safer at higher concentrations and more efficient in reducing TGF-β1, collagen type-1A2 and type-3A1 mRNA expression than QUR. In vivo studies confirmed that the EGCG hydrogel was efficient in improving the disease conditions compared to the standard treatment betamethasone injection with significant reduction in TGF-β1 and collagen concentrations with increase in mouth opening. EGCG can be considered as a potential, safer and efficient phytomolecule for OSF therapy and its mucoadhesive topical formulation help in the improvement of patient compliance without any side effects. Graphical abstract Highlights Potential polyphenols were shortlisted to treat oral submucous fibrosis (OSF) using in silico tools Epigallocatechin 3-gallate (EGCG) significantly reduced TGF-β1 and collagen both in vitro and in vivo EGCG hydrogel enhanced antioxidant defense, modulated inflammation by reducing TGF-β1 and improved mouth opening in OSF rat model.

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Section: Discussionmentioning

confidence: 90%

Polyphenol-based targeted therapy for oral submucous fibrosis

Mehta¹,

Paliwal²,

Muttigi³

et al. 2023

Inflammopharmacol

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“…As shown by authors, members of the TGF-β family of cytokines distinguish CAFs from oral cancer and from normal oral fibroblasts [ 28 ]. In other studies, the researchers investigated the role of TGF-β in the induction of fibrosis in another oral disorder, namely oral submucous fibrosis (OSF) [ 29 , 30 ]. OSF is a potentially malignant condition of the oral cavity, characterized by a generalized submucosal fibrosis [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

New Gene Markers for Metabolic Processes and Homeostasis in Porcine Buccal Pouch Mucosa during Cells Long Term-Cultivation—A Primary Culture Approach

Dyszkiewicz-Konwińska

Nawrocki²,

Huang

et al. 2018

IJMS

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The oral mucosal tissue is a compound structure composed of morphologically and physiologically different cell types. The morphological modification involves genetically determined lifespan, which may be recognized as the balance between cell survival and apoptosis. Although the biochemical processes and pathways in oral mucosa, with special regards to drug transport, delivery, and metabolism, are well known, the cellular physiological homeostasis in this tissue requires further investigation. The porcine buccal pouch mucosal cells (BPMCs) collected from 20 pubertal crossbred Landrace gilts, were used in this study. Immediately after recovery, the oral mucosa was separated micro-surgically, and treated enzymatically. The dispersed cells were transferred into primary in vitro culture systems for a long-term cultivation of 30 days. After each step of in vitro culture (IVC), the cells were collected for isolation of total RNA at 24 h, 7, 15, and 30 days of IVC. While the expression was analyzed for days 7, 15, and 30, the 24th hour was used as a reference for outcome calibration. The gene expression profile was determined using Affymetrix microarray assays and necessary procedures. In results, we observed significant up-regulation of SCARB1, PTGS2, DUSP5, ITGB3, PLK2, CCL2, TGFB1, CCL8, RFC4, LYN, ETS1, REL, LIF, SPP1, and FGER1G genes, belonging to two ontological groups, namely “positive regulation of metabolic process”, and “regulation of homeostatic process” at 7 day of IVC as compared to down-regulation at days 15 and 30. These findings suggest that the metabolic processes and homeostatic regulations are much more intense in porcine mucosal cells at day 7 of IVC. Moreover, the increased expression of marker genes, for both of these ontological groups, may suggest the existence of not only “morphological lifespan” during tissue keratinization, but also “physiological checkpoint” dedicated to metabolic processes in oral mucosa. This knowledge may be useful for preclinical experiments with drugs delivery and metabolism in both animals and humans.

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“…In the past few decades, accumulated studies have demonstrated that areca nuts can induce premalignant and malignant transformation of oral tissues. In animal model studies, areca nut extract (or the ingredient cocktail) can be an effective tumor initiator or promoter and can induce premalignant oral lesions, including submucosal fibrosis 9, 10 and squamous hyperplasia 11-13, or result in malignant transformation 13-16. For example, arecaidine displays a synergistic effect in the 7,12-dimethyl-benz(a)anthracene (DMBA)- induced tumor formation in the cheek pouch of hamster 15.…”

Section: Molecular Pathology Of Areca Nutmentioning

confidence: 99%

Multifaceted Mechanisms of Areca Nuts in Oral Carcinogenesis: the Molecular Pathology from Precancerous Condition to Malignant Transformation

Li¹,

Cheng²,

Lee³

et al. 2019

J. Cancer

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Oral cancer is one of the most frequent malignant diseases worldwide, and areca nut is a primary carcinogen causing this cancer in Southeast Asia. It has been widely reported that areca nut induced several cytotoxic effects in oral cells, including ROS generation, inflammation, tissue hypoxia, DNA damage, and cell invasion. Recently, through chronic exposure model, more extensive pathological effects due to areca nut have been found. These include the induction of autophagy, promotion of epithelial-mesenchymal transition, and facilitation of cancer stemness conversion. Clinical findings support these adverse effects. Oral submucosal fibrosis, a premalignant condition, is prevalent in the area with habitual chewing of areca nuts. Consistently, oral cancer patients with habitual chewing areca nut exhibit more aggressive phenotypes, including resistance to chemo-radiotherapy. In this review, we comprehensively discuss and concisely summarize the up-to-date molecular and cellular mechanisms by which areca nuts contribute to malignant transformation. This review may provide critical information regarding clinical applications in risk assessment, disease prevention, diagnosis, and personalized therapeutics for areca nut-induced oral malignancy.

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Evaluation of transforming growth factor beta1 gene in oral submucous fibrosis induced in Sprague-Dawley rats by injections of areca nut and pan masala (commercial areca nut product) extracts

Abstract: The study provides further evidence that arecanut and pan masala induce oral submucous fibrosisvia the TGF beta1 pathway.

Cited by 18 publications

References 0 publications

Polyphenol-based targeted therapy for oral submucous fibrosis

Polyphenol-based targeted therapy for oral submucous fibrosis

New Gene Markers for Metabolic Processes and Homeostasis in Porcine Buccal Pouch Mucosa during Cells Long Term-Cultivation—A Primary Culture Approach

Multifaceted Mechanisms of Areca Nuts in Oral Carcinogenesis: the Molecular Pathology from Precancerous Condition to Malignant Transformation

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