Aurintricarboxylic Acid Mitigates Cigarette Smoke Extract Induced Oxidative Stress and Pulmonary Inflammation via Inhibition of NF-ҡB/p65 Signalling
Creators: name: Devi, Kusum
name: Singh, Yatendra
name: Kanojiya, Sanjeev
name: Moharana, Baisakhi
Publisher: name: Taylor & Francis
Year: 2022
Subjects: subject: Biochemistry
subject: Medicine
subject: Microbiology
subject: FOS: Biological sciences
subject: Cell Biology
subject: Genetics
subject: Molecular Biology
subject: Physiology
subject: Pharmacology
subject: 39999 Chemical Sciences not elsewhere classified
subject: FOS: Chemical sciences
subject: Immunology
subject: FOS: Clinical medicine
subject: Cancer

description: Cigarette smoke (CS) induced emphysema and chronic pulmonary inflammation are major comorbidities of chronic obstructive pulmonary disease (COPD), a major cause of morbidity and mortality worldwide. CS exposure exacerbates pulmonary inflammation and compromises immunity to various infections. Aurintricarboxylic acid (ATA) is a polyanionic aromatic compound especially recognized for its anti-inflammatory, nucleic acid and protein interaction inhibition properties. The study was designed to investigate the anti-inflammatory role of ATA against cigarette smoke extract (CSE) induced pulmonary inflammation. Nicotine concentration was quantified in CSE by UPLC/MS technique. <i>In vitro</i>, fluorescence microscopy, flow cytometry was performed in CSE stimulated alveolar epithelial cells to determine the effect of ATA on oxidative stress mediated cellular apoptosis. <i>In vivo</i>, pulmonary inflammation was induced in male Wistar rats via a modified non–invasive intratracheal instillation of cigarette smoke extract (100 µl/animal) twice a week for 8 weeks and post-treated with ATA (10 mg/kg) intraperitoneally for 15 days. Lung homogenates were assessed for MDA and GSH. Lung tissues were subjected to western blotting and histopathological analysis. As result, ATA reduced CSE-induced chromatin condensation, fragmentation, cellular apoptosis in alveolar epithelial cells and apoptotic biomarkers expression including BAX, and Caspase-3 in lungs. ATA reduced inflammation by normalizing redox balance reflected by MDA/GSH levels. ATA obviated airspace enlargement, fibre deposition and immune cell infiltration. Reduced inflammation was accompanied by inhibition of inflammatory biomarkers TNF-α, TNFR1, TWEAK and NF-ҡB/p65 activation and nuclear translocation. ATA efficaciously diminished the oxidative stress and pulmonary inflammation associated with lung pathogenesis through TNF-α/TNFR1/NF-ҡB/p65 signalling pathway.HighlightsATA treatment attenuates CSE stimulated chromatin condensation, fragmentation, cellular apoptosis in alveolar epithelial cells.ATA treatment inhibits CSE stimulated activation and nuclear translocation of NF- ҡB/p65.ATA treatment diminishes CSE induced oxidant injury, apoptosis and emphysema like phenotypic changes in lungs.ATA inhibits lung inflammation via suppression of NF-ҡB/p65 signalling pathway. ATA treatment attenuates CSE stimulated chromatin condensation, fragmentation, cellular apoptosis in alveolar epithelial cells. ATA treatment inhibits CSE stimulated activation and nuclear translocation of NF- ҡB/p65. ATA treatment diminishes CSE induced oxidant injury, apoptosis and emphysema like phenotypic changes in lungs. ATA inhibits lung inflammation via suppression of NF-ҡB/p65 signalling pathway.