4.7 Article

3′5-Dimaleamylbenzoic Acid Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice

期刊

出版社

MDPI
DOI: 10.3390/ijms23147943

关键词

myofibroblasts; alpha-SMA; collagen; transforming growth factor-beta 1; oxidative stress; pro-oxidants

资金

  1. CONACYT [270189]
  2. CONACyT-Fondo de Ciencia Basica [cb-2016-01, 287162]
  3. SEP, PFCE-2018
  4. SEP, PFCE-2019
  5. [FORDECYT-PRONACES-53358/2020]

向作者/读者索取更多资源

This study suggests that 3'5-dimaleamylbenzoic acid (3'5-DMBA) could be a promising candidate for the treatment of idiopathic pulmonary fibrosis (IPF) by reducing fibrosis, inflammation, and oxidative damage.
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, alpha-SMA, and TGF-beta 1. 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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