Benzo (A) pyrene exposure alters alveolar epithelial and macrophage cells diversity and induces antioxidant responses in lungs

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 histo...

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Main Authors: Pooja Chauhan, Nitin Bhardwaj, Sumit Rajaura, Harish Chandra, Ashutosh Singh, Ram Babu, Neelu Jain Gupta
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Toxicology Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2214750024001604
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author Pooja Chauhan
Nitin Bhardwaj
Sumit Rajaura
Harish Chandra
Ashutosh Singh
Ram Babu
Neelu Jain Gupta
author_facet Pooja Chauhan
Nitin Bhardwaj
Sumit Rajaura
Harish Chandra
Ashutosh Singh
Ram Babu
Neelu Jain Gupta
author_sort Pooja Chauhan
collection DOAJ
description 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.
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spelling doaj-art-116b620e93d441478ce1e02f27d1cc0e2024-12-19T10:54:46ZengElsevierToxicology Reports2214-75002024-12-0113101777Benzo (A) pyrene exposure alters alveolar epithelial and macrophage cells diversity and induces antioxidant responses in lungsPooja Chauhan0Nitin Bhardwaj1Sumit Rajaura2Harish Chandra3Ashutosh Singh4Ram Babu5Neelu Jain Gupta6Department of Zoology and Environmental Science, Gurukula Kangri (Deemed to be University), Haridwar, Uttarakhand, IndiaDepartment of Zoology and Environmental Science, Gurukula Kangri (Deemed to be University), Haridwar, Uttarakhand, India; Corresponding author.Department of Zoology and Environmental Science, Gurukula Kangri (Deemed to be University), Haridwar, Uttarakhand, IndiaDepartment of Botany and Microbiology, Gurukula Kangri (Deemed to be University), Haridwar, Uttarakhand, IndiaDepartment of Biochemistry, Lucknow University, Lucknow, Uttar Pradesh, IndiaDepartment of Botany, Kirori Mal College, New Delhi, IndiaDepartment of Zoology, CCS University Campus Meerut, Uttar Pradesh, IndiaThis 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.http://www.sciencedirect.com/science/article/pii/S2214750024001604Benzo (a) pyreneEpithelial cellsInflammationLung cancerMacrophages
spellingShingle Pooja Chauhan
Nitin Bhardwaj
Sumit Rajaura
Harish Chandra
Ashutosh Singh
Ram Babu
Neelu Jain Gupta
Benzo (A) pyrene exposure alters alveolar epithelial and macrophage cells diversity and induces antioxidant responses in lungs
Toxicology Reports
Benzo (a) pyrene
Epithelial cells
Inflammation
Lung cancer
Macrophages
title Benzo (A) pyrene exposure alters alveolar epithelial and macrophage cells diversity and induces antioxidant responses in lungs
title_full Benzo (A) pyrene exposure alters alveolar epithelial and macrophage cells diversity and induces antioxidant responses in lungs
title_fullStr Benzo (A) pyrene exposure alters alveolar epithelial and macrophage cells diversity and induces antioxidant responses in lungs
title_full_unstemmed Benzo (A) pyrene exposure alters alveolar epithelial and macrophage cells diversity and induces antioxidant responses in lungs
title_short Benzo (A) pyrene exposure alters alveolar epithelial and macrophage cells diversity and induces antioxidant responses in lungs
title_sort benzo a pyrene exposure alters alveolar epithelial and macrophage cells diversity and induces antioxidant responses in lungs
topic Benzo (a) pyrene
Epithelial cells
Inflammation
Lung cancer
Macrophages
url http://www.sciencedirect.com/science/article/pii/S2214750024001604
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