Division of Pharmacology, CSIR-Central Drug Research Institute, Lucknow, India.
Academy of Scientific & Innovative Research (AcSIR), Kamla Nehru Nagar, Ghaziabad, India.
Toxicol Mech Methods. 2023 Jan;33(1):83-94. doi: 10.1080/15376516.2022.2090302. Epub 2022 Jul 4.
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. , 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. , pulmonary inflammation was induced in male Wistar rats 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-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 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-ҡB/p65.ATA treatment diminishes CSE-induced oxidant injury, apoptosis, and emphysema-like phenotypic changes in the lungs.ATA inhibits lung inflammation suppression of the NF-ҡB/p65 signaling pathway.
香烟烟雾（CS）引起的肺气肿和慢性肺部炎症是慢性阻塞性肺疾病（COPD）的主要合并症，这是全球发病率和死亡率的主要原因。CS 暴露会加重肺部炎症，并损害对各种感染的免疫力。金精三羧酸（ATA）是一种聚阴离子芳香族化合物，尤其因其抗炎、核酸和蛋白质相互作用抑制特性而受到认可。本研究旨在研究 ATA 对香烟烟雾提取物（CSE）引起的肺部炎症的抗炎作用。通过 UPLC/MS 技术定量测定 CSE 中的尼古丁浓度。荧光显微镜和流式细胞术用于测定 ATA 对 CSE 刺激的肺泡上皮细胞中氧化应激介导的细胞凋亡的影响。雄性 Wistar 大鼠中诱导肺部炎症，通过每周两次对动物进行改良的非侵入性气管内滴注香烟烟雾提取物（100μl/动物），共 8 周，然后腹膜内给予 ATA（10mg/kg）治疗 15 天。评估肺匀浆中的 MDA 和 GSH。对肺组织进行 Western 印迹和组织病理学分析。结果表明，ATA 减少了 CSE 诱导的肺泡上皮细胞中的染色质浓缩、碎裂和细胞凋亡，以及肺中 Bax 和 Caspase-3 等凋亡生物标志物的表达。ATA 通过使 MDA/GSH 水平正常化来纠正氧化还原平衡，从而减轻炎症。ATA 避免了气腔扩大、纤维沉积和免疫细胞浸润。炎症减轻伴随着抑制 TNF-α、TNFR1、TWEAK 和 NF-ҡB/p65 激活和核转位的炎症生物标志物。ATA 通过 TNF-α/TNFR1/NF-ҡB/p65 信号通路有效减轻与肺发病机制相关的氧化应激和肺部炎症。重点ATA 治疗可减轻 CSE 刺激的肺泡上皮细胞中的染色质浓缩、碎裂和细胞凋亡。ATA 治疗抑制 CSE 刺激的 NF-ҡB/p65 的激活和核转位。ATA 减轻 CSE 诱导的氧化损伤、细胞凋亡和肺组织中的肺气肿样表型改变。ATA 通过抑制 NF-ҡB/p65 信号通路抑制肺部炎症。
