Attenuation of Bleomycin-Induced Pulmonary Fibrosis in Rats with S-Allyl Cysteine.

Takuma Tsukioka,Shigeru Okada,Yukiko Minamiyama,Shinjiro Mizuguchi,Michihito Toda,Shigekazu Takemura

doi:10.3390/molecules22040543

Abstract

Pulmonary fibrosis is a complex disease with high mortality and morbidity. As there are currently no effective treatments, development of new strategies is essential for improving therapeutic outcomes. S-allyl cysteine (SAC) is a constituent of aged garlic extract that has demonstrated efficacy as an antioxidant and anti-inflammatory agent. The current study examines the effects of SAC on pulmonary fibrosis induced by a single intratracheal instillation of bleomycin (2.5 mg/kg). SAC was administered to rats as 0.15% SAC-containing diet from seven days prior to instillation up until the conclusion of the experiment (14 days post-instillation). SAC significantly reduced collagen mRNA expression and protein deposition (33.3 ± 2.7 μg/mg and 28.2 ± 2.1 μg/mg tissue in vehicle- and SAC-treated rats, respectively), and decreased fibrotic area, as assessed histologically. In the rats’ lungs, SAC also attenuated the increased expression of transforming growth factor-β1 (TGF-β1), a central regulator of myofibroblast recruitment, activation, and differentiation. While bleomycin instillation increased the number of myofibroblasts within the lung mesenchymal area, this change was significantly reduced by SAC treatment. SAC may exert efficacy as an anti-fibrotic by attenuating myofibroblast differentiation through TGF-β1-mediated fibroproliferative processes. Thus, our results indicate SAC may be useful for the prevention or treatment of pulmonary fibrosis.

Highlights

Pulmonary fibrosis is a complex disease with high mortality and morbidity [1]
We previously reported that S-allyl cysteine (SAC) decreased carbon tetrachloride (CCl4 )-induced acute liver injury by attenuating oxidative stress [9] and liver fibrosis [10]
We previously reported that SAC attenuated CCl4 -induced pulmonary fibrosis [15]

Summary

Introduction

Pulmonary fibrosis is a complex disease with high mortality and morbidity [1]. Pulmonary fibrosis is characterized by the infiltration of inflammatory cells, the generation of reactive oxygen species, fibroblast proliferation, and the deposition of extracellular matrix protein into the lung parenchyma.Anti-inflammatory drugs such as corticosteroids and immunosuppressive agents are widely used for pulmonary fibrosis treatment; there is no truly effective treatment for this disease [2,3,4].the development of new agents is essential for improving therapeutic efficacy. Pulmonary fibrosis is a complex disease with high mortality and morbidity [1]. Pulmonary fibrosis is characterized by the infiltration of inflammatory cells, the generation of reactive oxygen species, fibroblast proliferation, and the deposition of extracellular matrix protein into the lung parenchyma. Anti-inflammatory drugs such as corticosteroids and immunosuppressive agents are widely used for pulmonary fibrosis treatment; there is no truly effective treatment for this disease [2,3,4]. Pirfenidone treatment has been reported to provide a means of intervention for the clinical course of idiopathic pulmonary fibrosis (IPF) [5]. Though this is a promising candidate for improving

Methods

Results

Conclusion