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

Abstract

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.

Zingiber officinale-Derived Extracellular Vesicles Attenuate Bleomycin-Induced Pulmonary Fibrosis Trough Antioxidant, Anti-Inflammatory and Protease Activity in a Mouse Model

“…Subsequently, the tissues were incubated in Harrys Hematoxylin (Hycel, 738, Guadalaja, Mexico) for 5 min, washed, and set in acid ethanol, followed by an ammoniacal solution, then a yellowish eosin (Hycel, 688, Guadalajara, Mexico) for 10 min. Finally, they were dehydrated and mounted with synthetic resin for microscopic analysis (Primo Star, CARL ZEISS) at 20× magnification [30].…”

The identification of metabolism-related subtypes and potential treatments for idiopathic pulmonary fibrosis

“…Metabolomics has recently become a popular topic for researchers exploring health conditions in humans ( Surendran et al, 2022 ). Metabolomics has reportedly helped elucidate the pathological mechanism of IPF ( Roque and Romero, 2021 ; Gonzalez-Garcia et al, 2022 ; Wygrecka et al, 2023 ). Several studies have demonstrated that lipidomic markers can be used to diagnose IPF, indicating their involvement in lipid metabolism ( Yan et al, 2017 ; Rindlisbacher et al, 2018 ).…”