Chauhan Pooja, Bhardwaj Nitin, Rajaura Sumit, Chandra Harish, Singh Ashutosh, Babu Ram, Gupta Neelu Jain
Department of Zoology and Environmental Science, Gurukula Kangri (Deemed to be University), Haridwar, Uttarakhand, India.
Department of Botany and Microbiology, Gurukula Kangri (Deemed to be University), Haridwar, Uttarakhand, India.
Toxicol Rep. 2024 Oct 18;13:101777. doi: 10.1016/j.toxrep.2024.101777. eCollection 2024 Dec.
This study was designed to investigate the toxic effects of benzo (a) pyrene (BaP) in the lungs. Mice were repeatedly treated orally with BaP (50 mg/kg body weight, twice a week for four weeks) to induce a tumour. After 4 months of BaP administration, tumours were visible beneath the skin. The histopathological section of the lungs shows congestion of pulmonary blood vessels, alveolar hyperplasia, and concurrent epithelial hyperplasia with infiltrates of inflammatory cells also seen. Thereafter, a single-cell suspension of lung tissues was stained with fluorescently conjugated antibodies for the demarcation of alveolar epithelial (anti-mouse CD74 and podoplanin) and macrophage (F4/80 and CD11b) cells and measured by flow cytometry. The expression of antioxidant genes was assessed by qRT-PCR. The number of alveolar epithelial cells 1 (AEC1) increased, but the number of alveolar epithelial cells 2 (AEC2) and transitional alveolar epithelial cells (TAEC) was significantly decreased in tumour-bearing mice. The proportion of CD11b alveolar macrophages (AM) and interstitial macrophages (IM) was increased, but the proportion of F4/80 AM cells was reduced. The BaP administration significantly increased the ROS production in alveolar cells. The relative expression levels of antioxidant genes (SOD1, catalase, GPX1, and HIF-1α) were increased, but NRF2 expression was decreased in BaP-treated alveolar cells. The expression of anti-inflammatory (NF-κB) was also significantly increased. In conclusion, BaP exposure induced an inflammatory response, altered alveolar epithelial cell and macrophage diversity, and increased antioxidant responses in the lungs.
本研究旨在调查苯并（a）芘（BaP）对肺部的毒性作用。给小鼠口服BaP（50毫克/千克体重，每周两次，共四周）以诱导肿瘤。给予BaP 4个月后，皮肤下可见肿瘤。肺组织病理切片显示肺血管充血、肺泡增生，同时可见上皮增生并伴有炎性细胞浸润。此后，用荧光共轭抗体对肺组织单细胞悬液进行染色，以区分肺泡上皮细胞（抗小鼠CD74和血小板内皮细胞黏附分子）和巨噬细胞（F4/80和CD11b），并通过流式细胞术进行检测。通过qRT-PCR评估抗氧化基因的表达。荷瘤小鼠的肺泡上皮细胞1（AEC1）数量增加，但肺泡上皮细胞2（AEC2）和过渡性肺泡上皮细胞（TAEC）数量显著减少。CD11b肺泡巨噬细胞（AM）和间质巨噬细胞（IM）的比例增加，但F4/80 AM细胞的比例降低。给予BaP显著增加了肺泡细胞中的活性氧生成。抗氧化基因（SOD1、过氧化氢酶、GPX1和HIF-1α）的相对表达水平增加，但在BaP处理的肺泡细胞中NRF2表达降低。抗炎因子（NF-κB）的表达也显著增加。总之，暴露于BaP会诱导肺部炎症反应，改变肺泡上皮细胞和巨噬细胞的多样性，并增强抗氧化反应。
