Mirtazapine, an atypical antidepressant, mitigates lung fibrosis by suppressing NLPR3 inflammasome and fibrosis-related mediators in endotracheal bleomycin rat model
Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible lung disease with a poor prognosis. There is currently no definitive cure for IPF. The present study establishes a platform for the development of a novel therapeutic approach for the treatment of PF using the atypical antidepress...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-05-01
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| Series: | Biomedicine & Pharmacotherapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223003414 |
| _version_ | 1797857662481727488 |
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| author | Rasha Abdelhady Simona Cavalu Sameh Saber Rasha Elmowafy Nesreen Elsayed Morsy Samar Ibrahim Mahmoud Said Ibrahim Abdeldaiem Mervat Samy Marwa A. Abd-Eldayem Ahmed Shata Rehab Mohamed Elgharabawy |
| author_facet | Rasha Abdelhady Simona Cavalu Sameh Saber Rasha Elmowafy Nesreen Elsayed Morsy Samar Ibrahim Mahmoud Said Ibrahim Abdeldaiem Mervat Samy Marwa A. Abd-Eldayem Ahmed Shata Rehab Mohamed Elgharabawy |
| author_sort | Rasha Abdelhady |
| collection | DOAJ |
| description | Idiopathic pulmonary fibrosis (IPF) is a progressive and irreversible lung disease with a poor prognosis. There is currently no definitive cure for IPF. The present study establishes a platform for the development of a novel therapeutic approach for the treatment of PF using the atypical antidepressant, mirtazapine. In the endotracheal bleomycin rat model, mirtazapine interfered with the activation of NLRP3 inflammasome via downregulating the NLRP3 on the gene and protein expression levels. Accordingly, the downstream mediators IL-1β and IL-18 were repressed. Such observation is potentially a direct result of the reported improvement in oxidative stress. Additionally, mirtazapine corrected the bleomycin-induced disparities in the levels of the fibrogenic mediators TGF-β, PDGF-BB, and TIMP-1, in consequence, the lung content of hydroxyproline and the expression of α-SMA were reduced. Besides, mirtazapine curbed the ICAM-1 and the chemotactic cytokines MCP-1 and CXCL4. This protective property of mirtazapine resulted in improving the BALF total and differential cell counts, diminishing LDH activity, and reducing the BALF total protein. Moreover, the inflammation and fibrosis scores were accordingly lower. To conclude, we reveal for the first time the efficacy of mirtazapine as a potential treatment for PF. The combination of social isolation, sleep problems, breathing difficulties, and fear of death can lead to psychological distress and depression in patients with IPF. Hence, mirtazapine is a promising treatment option that may improve the prognosis for IPF patients due to its antifibrotic effects, as well as its ability to alleviate depressive episodes. |
| first_indexed | 2024-04-09T21:00:24Z |
| format | Article |
| id | doaj.art-0b3999f801e249079f312e2d9354efde |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-09T21:00:24Z |
| publishDate | 2023-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-0b3999f801e249079f312e2d9354efde2023-03-29T09:24:20ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-05-01161114553Mirtazapine, an atypical antidepressant, mitigates lung fibrosis by suppressing NLPR3 inflammasome and fibrosis-related mediators in endotracheal bleomycin rat modelRasha Abdelhady0Simona Cavalu1Sameh Saber2Rasha Elmowafy3Nesreen Elsayed Morsy4Samar Ibrahim5Mahmoud Said Ibrahim Abdeldaiem6Mervat Samy7Marwa A. Abd-Eldayem8Ahmed Shata9Rehab Mohamed Elgharabawy10Pharmacology and Toxicology Department, Faculty of Pharmacy, Fayoum University, Fayoum 63514, Egypt; Corresponding author.Faculty of Medicine and Pharmacy, University of Oradea, P-ta 1 Decembrie 10, 410087 Oradea, RomaniaDepartment of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, EgyptDepartment of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University, Mansoura 35516, EgyptPulmonary Medicine Department, Mansoura University Sleep Center, Faculty of Medicine, Mansoura University, Mansoura 35516, EgyptDepartment of Pharmacy Practice, Faculty of Pharmacy, Ahram Canadian University, Giza 12451, EgyptDepartment of Pharmacy Practice, Faculty of Pharmacy, Sinai University-Kantara branch, Ismailia 41636, EgyptDepartment of Clinical Pharmacology, Faculty of Medicine, Mansoura University, Mansoura 35516, EgyptDepartment of Pharmacology and Biochemistry, Faculty of Pharmacy, Horus University, New Damietta, EgyptDepartment of Clinical Pharmacology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt; Department of Clinical Pharmacy, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, EgyptPharmacology and Toxicology Department, Faculty of Pharmacy, Tanta University, Tanta 31527, EgyptIdiopathic pulmonary fibrosis (IPF) is a progressive and irreversible lung disease with a poor prognosis. There is currently no definitive cure for IPF. The present study establishes a platform for the development of a novel therapeutic approach for the treatment of PF using the atypical antidepressant, mirtazapine. In the endotracheal bleomycin rat model, mirtazapine interfered with the activation of NLRP3 inflammasome via downregulating the NLRP3 on the gene and protein expression levels. Accordingly, the downstream mediators IL-1β and IL-18 were repressed. Such observation is potentially a direct result of the reported improvement in oxidative stress. Additionally, mirtazapine corrected the bleomycin-induced disparities in the levels of the fibrogenic mediators TGF-β, PDGF-BB, and TIMP-1, in consequence, the lung content of hydroxyproline and the expression of α-SMA were reduced. Besides, mirtazapine curbed the ICAM-1 and the chemotactic cytokines MCP-1 and CXCL4. This protective property of mirtazapine resulted in improving the BALF total and differential cell counts, diminishing LDH activity, and reducing the BALF total protein. Moreover, the inflammation and fibrosis scores were accordingly lower. To conclude, we reveal for the first time the efficacy of mirtazapine as a potential treatment for PF. The combination of social isolation, sleep problems, breathing difficulties, and fear of death can lead to psychological distress and depression in patients with IPF. Hence, mirtazapine is a promising treatment option that may improve the prognosis for IPF patients due to its antifibrotic effects, as well as its ability to alleviate depressive episodes.http://www.sciencedirect.com/science/article/pii/S0753332223003414MirtazapinePulmonary fibrosisBleomycinNLRP3 inflammasomeTGF-β, IL-1β |
| spellingShingle | Rasha Abdelhady Simona Cavalu Sameh Saber Rasha Elmowafy Nesreen Elsayed Morsy Samar Ibrahim Mahmoud Said Ibrahim Abdeldaiem Mervat Samy Marwa A. Abd-Eldayem Ahmed Shata Rehab Mohamed Elgharabawy Mirtazapine, an atypical antidepressant, mitigates lung fibrosis by suppressing NLPR3 inflammasome and fibrosis-related mediators in endotracheal bleomycin rat model Biomedicine & Pharmacotherapy Mirtazapine Pulmonary fibrosis Bleomycin NLRP3 inflammasome TGF-β, IL-1β |
| title | Mirtazapine, an atypical antidepressant, mitigates lung fibrosis by suppressing NLPR3 inflammasome and fibrosis-related mediators in endotracheal bleomycin rat model |
| title_full | Mirtazapine, an atypical antidepressant, mitigates lung fibrosis by suppressing NLPR3 inflammasome and fibrosis-related mediators in endotracheal bleomycin rat model |
| title_fullStr | Mirtazapine, an atypical antidepressant, mitigates lung fibrosis by suppressing NLPR3 inflammasome and fibrosis-related mediators in endotracheal bleomycin rat model |
| title_full_unstemmed | Mirtazapine, an atypical antidepressant, mitigates lung fibrosis by suppressing NLPR3 inflammasome and fibrosis-related mediators in endotracheal bleomycin rat model |
| title_short | Mirtazapine, an atypical antidepressant, mitigates lung fibrosis by suppressing NLPR3 inflammasome and fibrosis-related mediators in endotracheal bleomycin rat model |
| title_sort | mirtazapine an atypical antidepressant mitigates lung fibrosis by suppressing nlpr3 inflammasome and fibrosis related mediators in endotracheal bleomycin rat model |
| topic | Mirtazapine Pulmonary fibrosis Bleomycin NLRP3 inflammasome TGF-β, IL-1β |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223003414 |
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