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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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.
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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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