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

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 8th 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.