Methylsulfonylmethane inhibits lung fibrosis progression, inflammatory response, and epithelial-mesenchymal transition via the transforming growth factor-Β1/SMAD2/3 pathway in rats exposed to both γ-radiation and Bisphenol-A

Abstract

Exposure to pollution is life-threatening, which may increase idiopathic pulmonary fibrosis progression. The current study aimed to explore the effect of methylsulfonyl methane as an anti-fibrotic agent against transforming growth factor-β1 (TGF-β1)/SMAD/Snail signaling-induced epithelial-mesenchymal transition factors imbalance in rats exposed to γ-radiation, and/or Bisphenol-A. Exposure to γ-radiation, and/or Bisphenol-A has triggered lung fibrosis accompanied by biochemical alterations confirmed by histopathological examination. MSM treatment has decreased neutrophil and lymphocytes percentage, protein accumulation, lactate dehydrogenase, and myeloperoxidase activities in the bronchoalveolar lavage fluid. Furthermore, methylsulfonylmethane ameliorated the inflammatory cytokines including tumor necrosis factor-α, interleukine-6, and TGF-β as well as attenuated the expressions of epithelial-mesenchymal transition related cell markers vimentin, Snail1, Slug, Twist1, α-SMA mRNA, and type 1 collagen were inhibited, while E-Cadherin expression was restored in the lung tissues. Phosphorylation of Smad 2/3 induced by exposure to γ-radiation, and/or Bisphenol-A was significantly inhibited by methylsulfonylmethane. Collectively, these findings reveal that methylsulfonylmethane exerts a potential anti-inflammatory and anti-fibrotic activity which could make it a potential therapeutic agent against IPF.

Keywords:

• Transforming growth factor-β1/SMAD/Snail
• epithelial mesenchymal transition
• methyl-sulfonyl-methane
• ionizing radiation
• Bisphenol-A

Acknowledgments

The authors thank Prof. Dr. Ahmad Othman (Professor of Pathology, Pathology Department, Faculty of Veterinary Medicine, Cairo University) for his examination of lung sections in this study.

Ethical approval

All the relevant international, national and/or institutional guidelines have been followed for the treatment and use of animals. All experiments under the National Institutes of Health guide for the care and use of laboratory animals (NIH Publications No. 8023, revised 1978) and approvals of the NCRRT independent Committee on Ethics for use and care of laboratory animals.

Disclosure statement

The authors declare that they have no conflict of interest.