Development of Epigallocatechin 3-gallate-Loaded Hydrogel Nanocomposites for Oral Submucous Fibrosis.

Oral submucous fibrosis (OSF) is a chronic progressive disease associated with increased collagen deposition and TGF-ß1 release. The current therapy and management have been a limited success due to low efficacy and adverse drug reactions. This study aimed to evaluate epigallocatechin 3-gallate (EGCG) encapsulated nanoparticles loaded mucoadhesive hydrogel nanocomposite (HNC) for OSF. Developed HNC formulations were evaluated for their permeation behaviour using in vitro as well as ex vivo studies, followed by evaluation of efficacy and safety by in vivo studies using areca nut extract-induced OSF in rats. The disease condition in OSF-induced rats was assessed by mouth-opening and biochemical markers. The optimized polymeric nanoparticles exhibited the required particle size (162.93 ± 13.81 nm), positive zeta potential (22.50 ± 2.94 mV) with better mucoadhesive strength (0.40 ± 0.002 N), and faster permeation due to interactions of the positively charged surface with the negatively charged buccal mucosal membrane. HNC significantly improved disease conditions by reducing TGF-ß1 and collagen concentration without showing toxicity and reverting the fibroid buccal mucosa to normal. Hence, the optimized formulation can be further tested to develop a clinically alternate therapeutic strategy for OSF.

Antifibrotic effect of silymarin on arecoline-induced fibrosis in primary human buccal fibroblasts: an in silico and in vitro analysis.

BACKGROUND: This study aimed to assess silymarin's anticancer and antifibrotic potential through in silico analysis and investigate its impact on in vitro arecoline-induced fibrosis in primary human buccal fibroblasts (HBF). METHODS & RESULTS: The study utilized iGEMDOCK for molecular docking, evaluating nine bioflavonoids, and identified silymarin and baicalein as the top two compounds with the highest target affinity, followed by subsequent validation through a 100ns Molecular Dynamic Simulation demonstrating silymarin's stable behavior with Transforming Growth Factor Beta. HBF cell lines were developed from tissue samples obtained from patients undergoing third molar extraction. Arecoline, a known etiological factor in oral submucous fibrosis (OSMF), was employed to induce fibrogenesis in these HBFs. The inhibitory concentration (IC50) of arecoline was determined using the MTT assay, revealing dose-dependent cytotoxicity of HBFs to arecoline, with notable cytotoxicity observed at concentrations exceeding 50µM. Subsequently, the cytotoxicity of silymarin was assessed at 24 and 72 h, spanning concentrations from 5µM to 200µM, and an IC50 value of 143µM was determined. Real-time polymerase chain reaction (qPCR) was used to analyze the significant downregulation of key markers including collagen, epithelial-mesenchymal transition (EMT), stem cell, hypoxia, angiogenesis and stress markers in silymarin-treated arecoline-induced primary buccal fibroblast cells. CONCLUSION: Silymarin effectively inhibited fibroblast proliferation and downregulated genes associated with cancer progression and EMT pathway, both of which are implicated in malignant transformation. To our knowledge, this study represents the first exploration of silymarin's potential as a novel therapeutic agent in an in vitro model of OSMF.

Curcumin in the treatment of oral submucous fibrosis: a systematic review and meta-analysis of randomized controlled trials.

The objective was to evaluate the efficacy of curcumin in improving mouth opening (MO), burning sensation (BS), and tongue protrusion (TP) symptoms in patients with oral submucous fibrosis (OSF). An electronic search up to November 2022 was conducted in the PubMed, Web of Science, Embase, EBSCO, ProQuest, and Cochrane Library databases to identify studies using curcumin in the treatment of OSF with comparison to control groups (drugs previously proven to be effective for OSF treatment) or placebo. Only randomized controlled trials (RCTs) were considered. RevMan 5.3 software was used for the meta-analysis. Thirteen RCTs met the eligibility criteria and were included in the analysis. The results showed no significant improvement in MO (in millimetres) for curcumin when compared to control at 1 month (P = 0.91), 2 months (P = 0.54), 3 months (P = 0.56), or 6 months (P = 0.17) of treatment. There was no significant difference in BS (assessed using a visual analogue scale) between curcumin and control after 1 month (P = 0.05), 2 months (P = 0.64), 3 months (P = 0.13), or 6 months (P = 0.56) of treatment. Compared with the control groups, treatment with curcumin for 1 month (P = 0.32), 2 months (P = 0.07), and 3 months (P = 0.14) did not significantly improve the TP (in millimetres) of patients. The administration of curcumin, whether topically applied or taken orally, did not confer statistically significant improvements in MO, BS, or TP in comparison to the control treatments, among patients with OSF. The results of this meta-analysis showed that compared to placebo, the application of curcumin for 6 months markedly alleviated BS (P < 0.001). Curcumin treatment in OSF reaches a clinically effective range, but more bioavailability-centred outcomes should be reported. Robust multicentre RCTs are warranted to elucidate the efficacy of curcumin in improving specific outcomes like MO, BS, and TP in patients with this condition. Defining the therapeutic role of this natural compound may provide an effective botanical alternative for managing OSF.

Antioxidant treatments in patients with oral submucous fibrosis: A systematic review.

INTRODUCTION: Oral submucous fibrosis (OSMF) is a well-known precancerous oral lesion, characterized by scarring, tissue fibrosis, and premalignant lesions. The goal of clinical treatment is to reduce inflammation and improve patients' quality of life by enhancing mouth opening among others. Antioxidant treatment has shown promising results in inducing regression of lesions and preventing OSMF in high-risk individuals. This study investigates the effectiveness of various antioxidant agents against OSMF. MATERIALS AND METHODS: The study followed PRISMA guidelines and searched three scientific databases: PubMed, Web of Science, and Scopus, using specific algorithms related to "antioxidant treatment," "burning sensation," and "mouth opening." The quality assessment of controlled clinical studies adhered to Cochrane guidelines. RESULTS: The analysis included 19 clinical trials comparing different treatments, including various antioxidants. Aloe vera, curcumin, and lycopene, among others, showed positive outcomes in treating OSMF by improving burning sensation, mouth opening, tongue protrusion, and cheek flexibility. CONCLUSION: Antioxidant therapies are found to be effective in treating OSMF, even when compared to conventional treatments such as corticosteroids. The study highlights the need for further research and standardization of clinical protocols.

Drug treatment for oral submucous fibrosis: an update.

OBJECTIVE: The aim of this review is to evaluate the different medicinal interventions available for the management of oral submucous fibrosis (OSF). MATERIALS AND METHODS: We conducted a comprehensive electronic search on PubMed, Web of Science, and Cochrane Library databases for articles related to OSF patients treated with medications from December 2011 to September 2022. GRADE system was used to evaluate the evidence quality. The reporting of the systematic review is in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. The main outcomes were the improvement of maximum mouth opening, burning sensation, cheek flexibility, and tongue protrusion. RESULTS: Twenty-nine randomized controlled trials (RCTs), five clinical trials (CCTs) were included, and the use of drugs for OSF treatment were evaluated. Drugs like steroids, hyaluronidase, pentoxifylline, lycopene, curcumin, dpirulina, aloe vera, omega3, oxitard, allicin, colchicine have been used. It was found that drugs with evidence high quality were salvia miltiorrhiza combined with triamcinolone acetonide, lycopene, pentoxifylline, curcumin, and aloe vera, and those with evidence moderate quality were allicin, colchicine, omega 3, and oxitard. CONCLUSION: Based on the results of our comprehensive analysis, for long-term treatment, we found lycopene with low side effects, whereas for relieving the symptoms of severe burning sensation, aloe vera is the most effective. Although the recent review has made some progress, drug therapy for OSF remains unclear, and more high-quality RCTs are needed to identify better treatments for OSF.

Polyphenol-based targeted therapy for oral submucous fibrosis.

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-ß1), 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-ß1, 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-ß1 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. Highlights Potential polyphenols were shortlisted to treat oral submucous fibrosis (OSF) using in silico tools Epigallocatechin 3-gallate (EGCG) significantly reduced TGF-ß1 and collagen both in vitro and in vivo EGCG hydrogel enhanced antioxidant defense, modulated inflammation by reducing TGF-ß1 and improved mouth opening in OSF rat model.

Comparative effectiveness of medicinal interventions for oral submucous fibrosis: A network meta-analysis.

OBJECTIVES: This network meta-analysis presents an exhaustive description and comparison of the available medical interventions for the management of oral submucous fibrosis (OSMF). MATERIALS AND METHODS: A systematic review and network meta-analysis was conducted after registration with PROSPERO. (PROSPERO ID CRD42022303441). Databases (PubMed, Cochrane, EMBASE, Web of Science, and others) were searched for randomized clinical trials (RCT) trials from inception till September 2022 for the medical interventions in OSMF. The primary outcome was the improvement in mouth opening. The secondary outcomes were improvement in burning sensation, tongue protrusion, and cheek flexibility. The interventions were ranked according to their efficacy based on the surface under the cumulative ranking. RESULTS: 47 studies including 2393 patients were assessed for quantitative analysis. For mouth opening, the combined treatment with steroid, hyaluronidase, and antioxidant was most effective [MD, 7.05 (95%CI 1.76,12.34)], followed by the combination of oral antioxidants with injectable steroids, [MD, 3.80 (95%CI -0.44,8.03)]. Additionally, the combined treatment with steroid, hyaluronidase, and antioxidant was most effective in reducing the burning sensation [MD, -8.62(-10.95,-6.30)], followed by aloe vera [MD, -8.45(-10.40,-6.49)] and pentoxifylline [MD -7.57(-9.46,-5.68)]. For tongue protrusion, curcumin was most effective followed by antioxidants. Most of the drugs used were reported to cause negligible or mild adverse effects. CONCLUSION: This network meta-analysis reported the efficacy of medicinal interventions in OSMF patients compared to the placebo in the improvement of mouth opening and burning sensation, and cheek flexibility. The methodological quality of included RCTs was low. Well-designed studies are recommended to obtain strong evidence.

Heterogeneity of outcome measures in the clinical trials of treatment for oral submucous fibrosis-Systematic review.

OBJECTIVE: This systematic review was performed to evaluate the range of outcome measures used in interventional trials for oral submucous fibrosis (OSF). MATERIALS AND METHODS: PubMed, Scopus, and Cochrane databases were searched to identify randomized controlled trials (RCTs) published from 2004 to 2018 about OSF treatment. All the outcome measures and measurement methods mentioned in the trials were extracted and analyzed. RESULTS: Out of 120 published papers, 12 RCTs that met the inclusion criteria were included. A total of 38 single outcome measures and 29 composite outcome measures were considered under four different outcome domains, of which clinical symptoms and clinical response were the most commonly used. The linear measurement of mouth opening (11 trials; 91.66%) and Visual Analogue Scale (10 trials, 83.33%) were the predominant measurement methods. CONCLUSIONS: This systematic review highlights the high heterogeneity in outcome measures in therapeutic RCTs of OSF. This lack of widely agreed standard outcome measures in OSF is a great concern as it prevents the comparison of studies and meta-analyses to gather evidence. There is a dire need of establishing a core outcome set for reporting in the future clinical trials that may help facilitate treatment choice for OSF to improve life quality of patients.

Efficacy of lycopene for management of oral potentially malignant disorders: A systematic review and meta-analysis.

OBJECTIVE: The aim of this study was to investigate the available evidence on the efficacy of lycopene in the management of oral potentially malignant disorders (OPMDs). STUDY DESIGN: PubMed, Scopus, Web of Science, Google Scholar, China National Knowledge Infrastructure, and ProQuest databases were searched up to April 20, 2022. All clinical trials that assessed the efficacy of lycopene (I) on the signs/symptoms (O) of patients with OPMDs (P) in comparison to either active control or placebo (C) were included. Meta-analysis was conducted using the RevMan software (Cochrane Collaboration, London, UK). RESULTS: A total of 27 clinical trials (20 on oral submucosa fibrosis [OSF], 5 on oral lichen planus [OLP], and 2 on leukoplakia) were included. Overall, lycopene was efficacious in reducing signs and symptoms of OSF, OLP, and leukoplakia. The pooled data revealed comparable efficacy of lycopene and prednisolone in reducing pain and promoting clinical resolution of OLP. Additionally, the pooled data reported comparable efficacy of lycopene and conventional controls in improving the mouth opening and tongue protrusion in patients with OSF. CONCLUSIONS: The results reveal promising effects of lycopene in alleviating signs and symptoms of OSF, OLP, and leukoplakia. However, owing to the observed heterogeneity and short follow-up periods, further well-designed studies with long-term therapy and follow-up are highly recommended.

5-aminolevulinic acid photodynamic therapy for extensive oral leukoplakia with concomitant oral submucous fibrosis: A case report.

BACKGROUND: Oral leukoplakia and oral submucous fibrosis are potentially malignant disorders of the oral cavity, with high rates of recurrence and malignant transformation. Notably, the malignant transformation rate of oral leukoplakia with concomitant oral submucous fibrosis is significantly higher than that of oral submucous fibrosis or oral leukoplakia alone. However, the management of these conditions is not well defined. Photodynamic therapy is a minimally invasive treatment modality that effectively targets oral potentially malignant disorders, such as oral leukoplakia, erythroleucoplakia, and verrucous hyperplasia, with the advantages of being repeatable and leaving no scarring. CASE PRESENTATION: We report the case of a 42-year-old man with concomitant oral leukoplakia and oral submucous fibrosis almost involving the entire right buccal mucosa, who underwent six sessions of topical 5-aminolevulinic acid-mediated photodynamic therapy. RESULTS: Photodynamic therapy successfully eradicated whitish plaques and improved mouth opening without any adverse effects. Although photodynamic therapy failed to completely reverse the pathological changes, grading of epithelial dysplasia did not progress and clinical recurrence was not found during the 10-month follow-up. CONCLUSION: In conclusion, topical 5-aminolevulinic acid-mediated photodynamic therapy appears safe and has excellent clinical efficacy against oral leukoplakia-concomitant oral submucous fibrosis, but long-term follow-up is necessary.

A biomaterial-based therapy using a sodium hyaluronate/bioglass composite hydrogel for the treatment of oral submucous fibrosis.

Oral submucous fibrosis (OSF) is a chronic, inflammatory and potentially malignant oral disorder. Its pathophysiology is extremely complex, including excessive collagen deposition, massive inflammatory infiltration, and capillary atrophy. However, the existing clinical treatment methods do not fully take into account all the pathophysiological processes of OSF, so they are generally low effective and have many side effects. In the present study, we developed an injectable sodium hyaluronate/45S5 bioglass composite hydrogel (BG/HA), which significantly relieved mucosal pallor and restricted mouth opening in OSF rats without any obvious side effects. The core mechanism of BG/HA in the treatment of OSF is the release of biologically active silicate ions, which inhibit collagen deposition and inflammation, and promote angiogenesis and epithelial regeneration. Most interestingly, silicate ions can overall regulate the physiological environment of OSF by down-regulating α-smooth muscle actin (α-SMA) and CD68 and up-regulating CD31 expression, as well as regulating the expression of pro-fibrotic factors [transforming growth factor-ß1 (TGF-ß1), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α) and tissue inhibitors of metalloproteinase-1 (TIMP-1)] and anti-fibrotic factors [interleukin-1ß (IL-1ß)] in macrophage. In conclusion, our study shows that BG/HA has great potential in the clinical treatment of OSF, which provides an important theoretical basis for the subsequent development of new anti-fibrotic clinical preparations. STATEMENT OF SIGNIFICANCE: : Oral submucous fibrosis (OSF) is a chronic, inflammatory and potentially malignant mucosal disease with significant impact on the quality of patients' life. However, the existing clinical treatments have limited efficacy and many side effects. There is an urgent need for development of specific drugs for OSF treatment. In the present study, bioglass (BG) composited with sodium hyaluronate solution (HA) was used to treat OSF in an arecoline-induced rat model. BG/HA can significantly inhibit collagen deposition, regulate inflammatory response, promote angiogenesis and repair damaged mucosal epithelial cells, and thereby mitigate the development of fibrosis in vivo.

Comparison Of Efficacy Of Steroids Alone And Combination Of Steroids With Hyaluronidase On Mouth Opening In Oral Submucous Fibrosis Patients.

BACKGROUND: Eventually Oral submucous fibrosis causes pronounced stiffness and failure to open the mouth. Objectives are to determine compare the efficacy of intralesional steroids alone and combination of steroids with hyaluronidase on mouth opening in oral submucous fibrosis. METHODS: It was a prospective comparative cohort study. Total of 74 patients both male and female having history of pan chewing and limited mouth opening and burning sensations were included in the study. Informed consent was taken and divided into two groups. Patients of group 1 were managed with mixture of betamethasone 1 ml and hyaluronidase 1500 IU and patients of group 2 were treated with only steroid injection of betamethasone 1 ml given intralesional, both injections were given intralesional, by multiple puncture technique and once a week and continued for twelve weeks (3 months). And data compiled and analyzed in SPSS-20. RESULTS: The mean age of group 1 was 40.027±6.97 years, and mean age of Group 2 was 37.351±5.48 years. In both groups, the greatest number of cases aged from 31-59 years. Compared to females in both groups, the majority of patients were males. In 32 (86.4)% patients of group 1 showed efficacy compared with 18[43.2] patients in group 2 [p-0.000]. Conclusion: In this study Intralesional steroids with hyaluronidase injections are more efficient for opening the mouth in patients with oral sub-mucus fibrosis.

Pentoxifylline - A Novel Adjunct in the Management of Patients with Oral Submucous Fibrosis in Terai Population of Nepal: A Prospective Case Control Study.

Oral submucous fibrosis is a premalignant condition largely seen in the South-Asian countries mainly due to the consumption of areca nut. Pentoxifylline is a methylxanthine derivative, with vasodilating, anti-inflammatory and immune modulatory properties and is believed to increase the vascularity of the mucosal layer. The study was conducted to clinically assess the effectiveness of orally given pentoxifylline with dexamethasone (4mg/ml) given intralesionally and hyaluronidase 1500 IU with 0.5ml of 2.0% lignocaine plus multivitamins in the management of Oral submucous fibrosis patients pertaining to the Terai belt of Nepal. This study was conducted as an experimental study consisting of 70 oral submucous fibrosis patients who were divided blindly into two groups i.e. control or standard drug group (n=35) and experimental drug group (n=35). Standard drug group were given biweekly intralesional injections of dexamethasone (4mg/ml) and hyaluronidase 1500IU with 0.5ml of 2.0% lignocaine plus one capsule of multivitamins daily for a period of 12 weeks whereas experimental drug group were given pentoxifylline tablets 400mg 3 times daily for 12 weeks in addition to the drugs given to the standard drug group. Variables considered in the study were burning sensation, mouth opening, tongue protrusion and cheek flexibility using visual analog scale, vernier caliper, cheek retractor and a metric scale. On comparing, statistically significant results were seen in experimental drug group as far as reduction in burning sensation (p<0.001) and increase in mouth opening (p<0.001) was concerned. As far as improvement in tongue protrusion and cheek flexibility were concerned, the results were appreciating but statistically not significant (p=0.231) and (p=0.251) respectively. This study showed the effectiveness of pentoxifylline as an adjunct in the routine management of oral submucous fibrosis.

Muscle Activity in Pre-Treatment and Post-Treatment Oral Submucous Fibrosis Patients: Electromyography Study.

Background: Oral submucous fibrosis (OSMF) is a premalignant condition of insidious onset which affects the oral mucosa, pharynx, and esophagus. The muscles of mastication are known to be affected resulting in limited mouth opening. Electromyography (EMG) is a sophisticated method of measuring and evaluating muscle activity. Previously, EMG was primarily utilized in medical sciences, but it is currently being used extensively in both the medical and dentistry fields. Objectives: The aim of the study is to evaluate the electromyographic activity of masseter muscle in OSMF patients before and after treatment and to compare with healthy controls. Materials and Methods: This prospective case-control clinical study comprised 180 OSMF patients who were divided into four groups and 45 healthy individuals served as the control group. The OSMF individuals were injected with hyaluronidase 1,500 IU mixed in 1.5 ml of dexamethasone and 0.5 ml of lignocaine HCL intralesionally twice a week for one month along with a basic physiotherapy regimen consisting of mouth exercises two times daily. The control subjects were given placebo capsules. The treatment was carried out for a month and the electromyographic masseter muscle activity was evaluated among the OSMF patients and control group before and after treatment. Results: The results revealed that the electromyographic activity of master muscles in OSMF patients showed increased activity when compared with healthy controls. Patients with OSMF showed decreased muscle activity after treatment. Conclusion: When compared with healthy controls, OSMF patients had higher electromyographic activity of the masseter muscles and the muscle activity was decreased following treatment. In OSMF patients, EMG may help in determining the involvement of the mastication and facial expression muscles. It can also be used as a diagnostic tool to assess the treatment outcome of muscle activity in OSMF patients.

Efficacy of topical tulsi (Ocimum sanctum) paste for the management of oral submucous fibrosis - A clinical study.

Context: Oral submucous fibrosis (OSMF) is a chronic insidious oral potentially malignant disorder characterized by increased collagen deposition and reduced collagen degradation causing burning sensation and difficulty in mouth opening. Aim: To assess the efficacy of topical Tulsi (Ocimum sanctum) paste for the management of OSMF. Settings and Design: Institution-based clinical trial. Materials and Methods: The study included a total of 60 OSMF patients categorized into three Groups A, B and C (20 in each) depending on the severity according to Lai DR et al. classification. The patients were advised for topical Tulsi paste application and were evaluated for the reduction in the burning sensation and improvement in mouth opening every month for 3 subsequent months using the numeric pain rating scale (NRS) and a Vernier calliper, respectively. Statistical Analysis: The baseline and 3-month recordings were subjected to inter- and intra-group statistical analysis using Kruskal-Wallis analysis of variance (ANOVA), Mann-Whitney U, one-way ANOVA, Tukey's multiple post-hoc and Wilcoxon matched-pairs tests. Results: There was a reduction in the burning sensation and improvement in the mouth opening in all three groups. The reduction in the burning sensation was statistically significant among all the groups (P < 0.05) and the NRS scores after 3 months among the three groups were not statistically significant (P > 0.05). There was a statistically significant difference (P < 0.05) in the improvement of mouth opening between Group A and B; A and C; but not between B and C. Conclusion: Tulsi paste showed a significant reduction in the burning sensation and improvement of the mouth opening thereby proving to be a safe and promising medicament for OSMF.

Efficacy of Curcumin in Combination with Intralesional Dexamethasone with Hyaluronidase in the Treatment of Oral Submucous Fibrosis: A Randomized Controlled Trial.

OBJECTIVE: The objective of this study was to determine the efficacy of curcumin in combination with  intralesional dexamethasone with hyaluronidase in the treatment of oral submucous fibrosis (OSF). METHODS: This randomized, double blind, parallel design, clinical trial was conducted at B.P. Koirala Institute of Health Sciences, Nepal. Thirty-four patients with clinically diagnosed OSF were randomized into two groups (17 participants in each) with baseline treatment of intralesional dexamethasone with hyaluronidase for 6 weeks for the both. Curcumin (2gm/day) was provided to Group A (Test) and Group B (Control) received placebo. Interincisal mouth opening, tongue protrusion, cheek flexibility and visual analogue scale (VAS) scoring of burning sensation of oral mucosa was recorded at baseline, 6, 8 and 12 weeks follow-up and independent t-test was used to compare the improvements in two groups. RESULTS: On comparing the 6 weeks and baseline values, in Group A and B the mean difference in mouth opening was 8.82±1.33 mm and 5.53±1.17 mm respectively (p<0.001), in cheek flexibility was 2.94±1.02 mm and 1.94±1.24 mm respectively (p=0.02) and in tongue protrusion was 6.23±1.48 and 3.65±1.37 mm respectively (p<0.001). The findings were consistent in the 8 weeks follow-up. In 12 weeks follow-up, on comparing with the baseline values, in Group A and B, the mean difference in mouth opening was 8.71±1.16 mm and 5.35±1.22 mm respectively (<0.001), ), in cheek flexibility was 2.81±1.01 mm and 1.76±1.35 mm respectively (p=0.02) and in tongue protrusion was 6.06±1.48 and 3.35±1.50 mm respectively (p<0.001). Both the arms showed 100% improvement in burning sensation in 6, 8 and 12 weeks follow-up. CONCLUSION: Curcumin in combination with intralesional dexamethasone with hyaluronidase is efficacious in the treatment of OSF.

A novel approach to develop an animal model for oral submucous fibrosis.

Epidemiological data have proved the association of consumption of areca nut with the causation of oral submucous fibrosis (OSF). OSF is a chronic inflammatory disease with the potential for malignant transformation from 7 to 13%. The establishment of animal models makes it easier for researchers to focus on the therapeutic options to combat this disease further. We developed and compared two areca nut extract (ANE) administration methods in Swiss albino mice to establish OSF. This study compared an invasive intrabuccal injection technique with a non-invasive intraoral droplet administration. The duration of induction was around 12 weeks. Histopathology (H&E, Masson's trichrome staining) and gene expression analysis (COL-I, COL-II, and α-SMA) were performed using RT-PCR to confirm the OSF in animals. Our study showed that ANE administration through the intraoral droplet method exhibited significantly higher fibrosis than the intrabuccal injections, as evidenced by the H&E and Masson's trichrome staining. Furthermore, intraoral administration of ANE significantly upregulated the mRNA expression of COL-I, COL-II, and α-SMA, as revealed by the RT-PCR analysis. The non-invasive droplet method could simulate the absorption of areca nut seen in humans through daily dosing. This study establishes the intraoral droplet method as an efficient and non-invasive method to administer the ANE to develop OSF. These findings will aid in the efficient development of OSF animal models for interventional studies, including screening novel drugs in the reversal of the OSF.

Oral Fibrosis and Oral Cancer: From Molecular Targets to Therapeutics.

Oral submucous fibrosis (OSF) belongs to a group of potentially malignant disorders that are characterized by the progressive fibrosis of the lining mucosa as well as an increasing loss of tissue mobility [...].

Clinical Assessment of Efficacy of Omega 3 in Oral Submucous Fibrosis Patients - A Randomized Controlled Trial.

BACKGROUND: Oral submucous fibrosis (OSMF) is a chronic, potentially malignant condition affecting the oral cavity. Omega 3 has shown innumerable health benefits in yesteryears. So, the aim of the study was to evaluate the efficacy of Omega 3 in the medical management of this disease. METHODS: A randomized controlled trial was designed and 48 clinically confirmed patients of OSMF (24 in each group) completed the study. Patients of both the groups were given biweekly intralesional injections of dexamethasone 1.5ml, hyaluronidase 1500 IU mixed with lignocaine for 6 weeks. Additionally, group A received a placebo (lactose capsule) for 3 months while group B received 1gm of omega 3 (flaxseed oil) three times daily continuously for 3 months. Patients were followed every month for 3 months and then, after 6 months and one year. RESULTS: During the first two months, improvement was observed in both the groups independently but intergroup comparison showed no significant difference. However, after 3 months statistically significant (p<0.05) improvement among all three clinical parameters i.e. inter-incisal distance (mean improvement in group A = 3.79±1.07mm and group B = 6.58±1.24mm, p=0.019), tongue protrusion (mean improvement in group A = 1.87±1.54mm and group B = 4.62±1.78mm, p=0.044) and cheek flexibility (mean improvement in group A = 2.08±1.38mm and group B = 3.50±1.84mm, p=0.035) was observed in group B when compared to group A. In contrast, statistically significant improvement in burning sensation was observed after one month itself in group B when compared to group A (mean drop in group A = 2.5±0.78 points and group B = 6.0±1.144 points, p<0.05). CONCLUSION: Omega 3 in conjunction with intralesional injections is an effective therapy when compared to intralesional injections alone in treatment of patients with OSMF (grade II and III) with no side effects.

Evaluating the Oral-Health-Related Quality of Life of Oral Submucous Fibrosis Patients before and after Treatment Using the OHIP-14 Tool.

The objective of the present study was to assess the oral-health-related quality of life (OHRQoL) of oral submucous fibrosis (OSMF) patients before and after standard treatment. A convenient sampling technique was used to recruit the clinically diagnosed patients of OSMF (n = 130). Based on the medical treatment, the patients were randomly divided into two study groups (group A and B). The group A patients received submucosal intralesional injections of dexamethasone (2 mL; 4 gm/mL), while group B patients received hyaluronidase (1500 IU). Both the group A and B patients received respective medical therapy biweekly for a period of five weeks. At the follow up visit (6 months), the impact of treatment on OHRQoL was assessed using the Oral Health Impact Profile-14 (OHIP-14). Data were analyzed by a chi-square test for quantitative variables and an independent t-test for qualitative variables. The comparison of all clinical parameters before and after treatment was performed by a paired t-test. The results after treatment showed that there was a significant improvement in all domains of OHIP-14 (p = 0.001) except psychological disability (p = 0.243). In addition, the OHRQoL of patients was significantly improved following the treatment.