Aurintricarboxylic acid mitigates cigarette smoke extract induced oxidative stress and pulmonary inflammation via inhibition of NF-Ò¡B/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 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 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-α, TNFR1, TWEAK, and NF-Ò¡B/p65 activation and nuclear translocation. ATA efficaciously diminished the oxidative stress and pulmonary inflammation associated with lung pathogenesis through TNF-α/TNFR1/NF-Ò¡B/p65 signaling pathway. HIGHLIGHTSATA treatment attenuates CSE-stimulated chromatin condensation, fragmentation, and cellular apoptosis in alveolar epithelial cells.ATA treatment inhibits CSE stimulated activation and nuclear translocation of NF-Ò¡B/p65.ATA treatment diminishes CSE-induced oxidant injury, apoptosis, and emphysema-like phenotypic changes in the lungs.ATA inhibits lung inflammation via suppression of the NF-Ò¡B/p65 signaling pathway.

Aurintricarboxylic acid and Evans Blue represent two different classes of anionic compounds which selectively inhibit the cytopathogenicity of human T-cell lymphotropic virus type III/lymphadenopathy-associated virus.

Aurintricarboxylic acid, an anionic triphenylmethane dye, and Evans Blue, an anionic compound structurally related to suramin, are, like suramin itself, inhibitors of human T-cell lymphotropic virus type III (HTLV-III)/-lymphadenopathy-associated virus (LAV) in vitro. These compounds may be targeted, at least in part, at the HTLV-III/LAV reverse transcriptase. The lack of any appreciable cytostatic action of aurintricarboxylic acid, Evans Blue and suramin against several murine and human cell lines, their inability to inhibit cellular DNA, RNA and protein synthesis, and their high lethal dose-50 (greater than or equal to 0.340 g/kg) for NMRI mice point to the selectivity of the compounds as inhibitors of HTLV-III/LAV.