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3′5-Dimaleamylbenzoic Acid Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice
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-D...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319702/ https://www.ncbi.nlm.nih.gov/pubmed/35887292 http://dx.doi.org/10.3390/ijms23147943 |
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author | González-García, Karina López-Martínez, Armando Velázquez-Enríquez, Juan Manuel Zertuche-Martínez, Cecilia Carrasco-Torres, Gabriela Sánchez-Navarro, Luis Manuel Villa-Treviño, Saúl Baltiérrez-Hoyos, Rafael Vásquez-Garzón, Verónica Rocío |
author_facet | González-García, Karina López-Martínez, Armando Velázquez-Enríquez, Juan Manuel Zertuche-Martínez, Cecilia Carrasco-Torres, Gabriela Sánchez-Navarro, Luis Manuel Villa-Treviño, Saúl Baltiérrez-Hoyos, Rafael Vásquez-Garzón, Verónica Rocío |
author_sort | González-García, Karina |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9319702 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-93197022022-07-27 3′5-Dimaleamylbenzoic Acid Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice González-García, Karina López-Martínez, Armando Velázquez-Enríquez, Juan Manuel Zertuche-Martínez, Cecilia Carrasco-Torres, Gabriela Sánchez-Navarro, Luis Manuel Villa-Treviño, Saúl Baltiérrez-Hoyos, Rafael Vásquez-Garzón, Verónica Rocío Int J Mol Sci Article 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. MDPI 2022-07-19 /pmc/articles/PMC9319702/ /pubmed/35887292 http://dx.doi.org/10.3390/ijms23147943 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article González-García, Karina López-Martínez, Armando Velázquez-Enríquez, Juan Manuel Zertuche-Martínez, Cecilia Carrasco-Torres, Gabriela Sánchez-Navarro, Luis Manuel Villa-Treviño, Saúl Baltiérrez-Hoyos, Rafael Vásquez-Garzón, Verónica Rocío 3′5-Dimaleamylbenzoic Acid Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice |
title | 3′5-Dimaleamylbenzoic Acid Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice |
title_full | 3′5-Dimaleamylbenzoic Acid Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice |
title_fullStr | 3′5-Dimaleamylbenzoic Acid Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice |
title_full_unstemmed | 3′5-Dimaleamylbenzoic Acid Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice |
title_short | 3′5-Dimaleamylbenzoic Acid Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice |
title_sort | 3′5-dimaleamylbenzoic acid attenuates bleomycin-induced pulmonary fibrosis in mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319702/ https://www.ncbi.nlm.nih.gov/pubmed/35887292 http://dx.doi.org/10.3390/ijms23147943 |
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