3′5-Dimaleamylbenzoic Acid Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice
| Autor: | Karina González-García, Armando López-Martínez, Juan Manuel Velázquez-Enríquez, Cecilia Zertuche-Martínez, Gabriela Carrasco-Torres, Luis Manuel Sánchez-Navarro, Saúl Villa-Treviño, Rafael Baltiérrez-Hoyos, Verónica Rocío Vásquez-Garzón |
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| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Organic Chemistry
Anti-Inflammatory Agents General Medicine Catalysis Idiopathic Pulmonary Fibrosis Computer Science Applications Inorganic Chemistry Mice Inbred C57BL Transforming Growth Factor beta1 Bleomycin Mice Animals Collagen Physical and Theoretical Chemistry Molecular Biology Lung myofibroblasts α-SMA collagen transforming growth factor-β1 oxidative stress pro-oxidants Spectroscopy |
| Zdroj: | International Journal of Molecular Sciences; Volume 23; Issue 14; Pages: 7943 |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms23147943 |
| Popis: | Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by parenchymal scarring, leading progressively to alveolar architecture distortion, respiratory failure, and eventually death. Currently, there is no effective treatment for IPF. Previously, 3′5-dimaleamylbenzoic acid (3′5-DMBA), a maleimide, demonstrated pro-apoptotic, anti-inflammatory, and anti-cancer properties; however, its potential therapeutic effects on IPF have not been addressed. Bleomycin (BLM) 100 U/kg was administered to CD1 mice through an osmotic minipump. After fourteen days of BLM administration, 3′5-DMBA (6 mg/kg or 10 mg/kg) and its vehicle carboxymethylcellulose (CMC) were administered intragastrically every two days until day 26. On day 28, all mice were euthanized. The 3′5-DMBA effect was assessed by histological and immunohistochemical staining, as well as by RT-qPCR. The redox status on lung tissue was evaluated by determining the glutathione content and the GSH/GSSG ratio. 3′5-DMBA treatment re-established typical lung histological features and decreased the expression of BLM-induced fibrotic markers: collagen, α-SMA, and TGF-β1. Furthermore, 3′5-DMBA significantly reduced the expression of genes involved in fibrogenesis. In addition, it decreased reduced glutathione and increased oxidized glutathione content without promoting oxidative damage to lipids, as evidenced by the decrease in the lipid peroxidation marker 4-HNE. Therefore, 3′5-DMBA may be a promising candidate for IPF treatment. |
| Databáze: | OpenAIRE |
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