Assessment of fibrosis induced by Bleomycin in a rat model that resembles Oral Submucous Fibrosis

Abstract

Background and Objective: Oral submucous fibrosis (OSF) is a precancerous disease that is characterized by subepithelial fibrosis of the oral cavity. Bleomycin is a chemotherapeutic antibiotic which was used in animal models of pulmonary fibrosis as fibrosis is one of the major side effects of Bleomycin in human cancer therapy. The aim of this study was to evaluate the degree of fibrosis in OSF induced by Bleomycin in a rat model using Van-Gieson stain and studying the expression of TGF-β1 and SMAD-3. Materials and Methods:A total of fifty adult female albino rats were used and divided into four test groups (ten animals each) according to the duration of treatment (2, 4, 6 and 8 weeks). Another ten animals were used as control group. Bleomycin at a concentration of 1mg/ml was maintained and was injected subcutaneously into one side of the cheek mucosa of the rats daily. Meanwhile, the rats of the control group were injected with saline. Then the dissected buccal mucosae of the rats were evaluated by H&E stain, Van-Gieson special stain, TGF-β1 immunostaining and determination of SMAD-3 gene level by qRT-PCR. Results:The histological findings were similar to that of OSF in humans. The mean value of each of Van-Gieson, TGF-β1 in addition to SMAD-3 gene expression gradually increased by time to reach its highest level at 8 th week of the experiment. Meanwhile, the lowest mean area percent was recorded in the control group. Conclusion:The histological changes induced by Bleomycin in a rat model gave a fibrotic response similar to that of OSF in humans. Downregulation of TGF-β1/SMAD-3 signaling could provide a valuable method for treatment of OSF.