Aprepitant exerts anti-fibrotic effect via inhibition of TGF-β/Smad3 pathway in bleomycin-induced pulmonary fibrosis in rats |
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| Institution: | 1. Department of Pharmacology, Faculty of Medicine, Minia University, 61511 Minia, Egypt;2. Departments of Biochemistry, Faculty of Medicine, Minia University, 61511 Minia, Egypt;3. Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt;1. Shaanxi Key Laboratory of Earth Surface System and Environmental Carrying Capacity, College of Urban and Environmental Sciences, Northwest University, Xi''an 710127, China;2. State Key Laboratory of Marine Pollution and Department of Chemistry, City University of Hong Kong, Kowloon, Hong Kong, China;1. College of Ecological Technology and Engineering, Shanghai Institute of Technology, Shanghai 201418, PR China;2. Jiaxing Tongji Institute for Environment, Jiaxing, Zhejiang 314051, PR China;3. College of Environmental Science and Engineering, Tongji University, Shanghai 200092, PR China;1. School of Life Science, College of Environment and Resource, Shanxi University, Taiyuan 030006, China;2. Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Shanxi Medical University, Taiyuan 030001, China;1. Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Rókus u. 2, Pécs H-7624, Hungary;2. Food Biotechnology Research Group, János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, Pécs H-7624, Hungary;3. Department of Environmental Toxicology, Institute of Aquaculture and Environmental Safety, Hungarian University of Agriculture and Life Sciences, Páter Károly u. 1, Gödöll? H-2100, Hungary;4. Lab-on-a-Chip Research Group, János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, Pécs H-7624, Hungary;5. Department of Laboratory Medicine, Medical School, University of Pécs, Ifjúság útja 13, Pécs H-7624, Hungary;6. CycloLab Cyclodextrin Research & Development Laboratory, Ltd., Illatos út 7, Budapest H-1097, Hungary;1. School of Public Health, Southwest Medical University, Luzhou 646000, China;2. Department of Clinical Laboratory, 404 Hospital of Mianyang, Mianyang 621000, China;3. School of Pharmacy, Southwest Medical University, Luzhou 646000, China;4. State Key Laboratory of Coal Mine Disaster Dynamics and Control, Chongqing University, Chongqing 400044, China;5. School of Environmental and Resource, Southwest University of Science and Technology, Mianyang 621010, China |
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| Abstract: | Bleomycin is a well-recognized antineoplastic drug. However, pulmonary fibrosis (PF) is considered to be the principal drawback that greatly limits its use. Here, we sought to investigate ability of the neurokinin receptor 1 blocker, aprepitant, to prevent PF caused by bleomycin. Male adult Wistar rat groups were given a single intratracheal injection of bleomycin, either alone or in combination with aprepitant therapy for 3 or 14 days. Collagen deposition and a rise in transforming growth factor beta (TGF-β) immunoreactivity in lung tissue serve as evidence of bleomycin-induced PF. The serum levels of lactate dehydrogenase, alkaline phosphatase, and total antioxidant improved after aprepitant therapy.Additionally, it reduced the protein expressions of interferon alpha, tumor necrosis factor alpha, and lung lipid peroxidation. Moreover, aprepitant treatment led to an increase in the antioxidant indices glutathione, glutathione peroxidase, and catalase. Aprepitant is postulated to protect against bleomycin-induced PF by decreasing TGF-β, phosphorylating Smad3, and increasing interleukin 37, an anti-fibrotic cytokine, and G Protein-coupled Receptor Kinase 2. Aprepitant for 14 days considerably exceeded aprepitant for 3 days in terms of improving lung damage and having an anti-fibrotic impact. In conclusion, aprepitant treatment for 14 days may be used as an adjuvant to bleomycin therapy to prevent PF, mostly through inhibiting the TGF-/p-Smad3 fibrotic pathway. |
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| Keywords: | Aprepitant Bleomycin Pulmonary fibrosis TGF-β Smad3 |
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