دورية أكاديمية
Autophagy modulation by irbesartan mitigates the pulmonary fibrotic alterations in bleomycin challenged rats: Comparative study with rapamycin.
| العنوان: | Autophagy modulation by irbesartan mitigates the pulmonary fibrotic alterations in bleomycin challenged rats: Comparative study with rapamycin. |
|---|---|
| المؤلفون: | Alsayed HA; Department of Clinical Pharmacology, Faculty of Medicine, Suez Canal University, 41522 Ismailia, Egypt., Mohammad HMF; Department of Clinical Pharmacology, Faculty of Medicine, Suez Canal University, 41522 Ismailia, Egypt; Central Laboratory, Center of Excellence in Molecular and Cellular Medicine (CEMCM), Faculty of Medicine, Suez Canal University, 41522 Ismailia, Egypt., Khalil CM; Department of Clinical Pharmacology, Faculty of Medicine, Suez Canal University, 41522 Ismailia, Egypt., El-Kherbetawy MK; Department of Pathology, Faculty of Medicine, Suez Canal University, 41522 Ismailia, Egypt., Elaidy SM; Department of Clinical Pharmacology, Faculty of Medicine, Suez Canal University, 41522 Ismailia, Egypt. Electronic address: samah_elaidi@med.suez.edu.eg. |
| المصدر: | Life sciences [Life Sci] 2022 Aug 15; Vol. 303, pp. 120662. Date of Electronic Publication: 2022 May 28. |
| نوع المنشور: | Comparative Study; Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 0375521 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0631 (Electronic) Linking ISSN: 00243205 NLM ISO Abbreviation: Life Sci Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: <2008->: Amsterdam : Elsevier Original Publication: Oxford; Elmsford, N. Y. [etc.] Pergamon Press. |
| مواضيع طبية MeSH: | Pulmonary Fibrosis*/chemically induced , Pulmonary Fibrosis*/drug therapy , Pulmonary Fibrosis*/metabolism, Animals ; Autophagy ; Bleomycin/toxicity ; Epithelial-Mesenchymal Transition ; Irbesartan/pharmacology ; Irbesartan/therapeutic use ; Mammals/metabolism ; Rats ; Sirolimus/pharmacology ; Sirolimus/therapeutic use ; TOR Serine-Threonine Kinases/metabolism ; Transforming Growth Factor beta1/metabolism |
| مستخلص: | Aims: In pulmonary fibrosis, autophagy handles the maintenance of alveolar epithelial cells, prevents epithelial-mesenchymal transition (EMT), and controls collagen turnover. The mammalian target of rapamycin (mTOR) and its translational-dependent proteins are essential regulators of autophagy. Irbesartan (IRB) has earlier ameliorative effects in experimental pulmonary fibrosis. The current study aimed to explore therapeutic autophagy-modulated pulmonary fibrotic changes by IRB versus rapamycin (RAPA) in bleomycin (BLM)-challenged rats. Materials and Methods: A single intratracheal BLM dose at day (0), IRB in different doses (10, 20, and 40 mg/kg) or RAPA (2.5 mg/kg) was given daily for 14 continuous days. Key Findings: IRB significantly diminished the fibrotic lung scores. Pulmonary levels of transforming growth factor (TGF)-β1 and hydroxyproline exhibited marked attenuation in IRB (40 mg/kg)-treated rats compared to other treated groups. IRB (40 mg/kg) was not significantly different from RAPA. It downregulated the fibrotic lung phosphorylated mammalian target of rapamycin (p-mTOR) levels and augmented lung Unc-51-like autophagy activating kinase 1 (ULK1), LC3-I and LC3-II more than IRB (10 and 20 mg/kg)-treated fibrotic groups. Significance: Autophagic effects via the mTOR signalling pathway may play a role in IRB's antifibrotic effects. Consideration of IRB as a therapeutic antifibrotic agent in pulmonary fibrosis needs further experimental and clinical long-term validation, especially in comorbid with primary hypertension, heart failure, and diabetic renal insults. (Copyright © 2022 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Bleomycin; Experimental pulmonary fibrosis; Irbesartan; Macroautophagy; Mammalian target of rapamycin; Rapamycin |
| المشرفين على المادة: | 0 (Transforming Growth Factor beta1) 11056-06-7 (Bleomycin) EC 2.7.11.1 (TOR Serine-Threonine Kinases) J0E2756Z7N (Irbesartan) W36ZG6FT64 (Sirolimus) |
| تواريخ الأحداث: | Date Created: 20220531 Date Completed: 20220617 Latest Revision: 20220621 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1016/j.lfs.2022.120662 |
| PMID: | 35636582 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1879-0631 |
|---|---|
| DOI: | 10.1016/j.lfs.2022.120662 |