Aurintricarboxylic acid mitigates cigarette smoke extract induced oxidative stress and pulmonary inflammation via inhibition of NF-κB/p65 signaling

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. In vitro, fluorescence microscopy, and flow cytometry was performed in CSE stimulated alveolar epithelial cells to determine the effect of ATA on oxidative stress-mediated cellular apoptosis. In vivo, pulmonary inflammation was induced in male Wistar rats via a modified non-invasive intratracheal instillation of cigarette smoke extract (100 mu l/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 the lungs. ATA reduced inflammation by normalizing redox balance reflected by MDA/GSH levels. ATA obviated airspace enlargement, fiber deposition, and immune cell infiltration. Reduced inflammation was accompanied by inhibition of inflammatory biomarkers TNF-alpha, TNFR1, TWEAK, and NF-kappa B/p65 activation and nuclear translocation. ATA efficaciously diminished the oxidative stress and pulmonary inflammation associated with lung pathogenesis through TNF-alpha/TNFR1/NF-kappa B/p65 signaling pathway.

Automated summary

This study found that Aurintricarboxylic acid (ATA) can alleviate cigarette smoke extract (CSE)-induced pulmonary inflammation by regulating the TNF-alpha/TNFR1/NF-kappa B/p65 signaling pathway. ATA not only reduced cellular apoptosis in alveolar epithelial cells, but also decreased the expression of inflammatory biomarkers and the level of oxidative stress. Furthermore, ATA also reduced fiber deposition and immune cell infiltration in the lungs.