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Role of Lung P450 Oxidoreductase in Paraquat-Induced Collagen Deposition in the Lung
Paraquat (PQ) is an agrochemical known to cause pulmonary fibrosis. PQ-induced collagen deposition in the lung is thought to require enzymatic formation of PQ radicals, but the specific enzymes responsible for this bioactivation event in vivo have not been identified. We tested the hypothesis that l...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8868258/ https://www.ncbi.nlm.nih.gov/pubmed/35204102 http://dx.doi.org/10.3390/antiox11020219 |
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author | Kovalchuk, Nataliia Jilek, Joseph L. Van Winkle, Laura S. Cherrington, Nathan J. Ding, Xinxin |
author_facet | Kovalchuk, Nataliia Jilek, Joseph L. Van Winkle, Laura S. Cherrington, Nathan J. Ding, Xinxin |
author_sort | Kovalchuk, Nataliia |
collection | PubMed |
description | Paraquat (PQ) is an agrochemical known to cause pulmonary fibrosis. PQ-induced collagen deposition in the lung is thought to require enzymatic formation of PQ radicals, but the specific enzymes responsible for this bioactivation event in vivo have not been identified. We tested the hypothesis that lung P450 oxidoreductase (POR or CPR) is important in PQ-induced lung fibrosis in mice. A lung-Cpr-null mouse model was utilized, which undergoes doxycycline-induced, Cre recombinase-mediated deletion of the Por gene specifically in airway Club cells and alveolar type 2 cells in the lung. The lungs of lung-Cpr-null mice and their wild-type littermates were collected on day 15 after a single intraperitoneal injection of saline (control) or PQ (20 mg/kg). Lung tissue sections were stained with picrosirius red for detection of collagen fibrils. Fibrotic lung areas were found to be significantly smaller (1.6-fold for males and 1.4-fold for females) in PQ-treated lung-Cpr-null mice than in sex- and treatment-matched wild-type mice. The levels of collagen in lung tissue homogenate were also lower (1.4–2.3-fold; p < 0.05) in PQ-treated lung-Cpr-null mice compared to PQ-treated wild-type mice. In contrast, plasma PQ toxicokinetic profiles were not different between sex-matched wild-type and lung-Cpr-null mice. Taken together, these results indicate that lung POR plays an important role in PQ-induced pulmonary fibrosis. |
format | Online Article Text |
id | pubmed-8868258 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-88682582022-02-25 Role of Lung P450 Oxidoreductase in Paraquat-Induced Collagen Deposition in the Lung Kovalchuk, Nataliia Jilek, Joseph L. Van Winkle, Laura S. Cherrington, Nathan J. Ding, Xinxin Antioxidants (Basel) Article Paraquat (PQ) is an agrochemical known to cause pulmonary fibrosis. PQ-induced collagen deposition in the lung is thought to require enzymatic formation of PQ radicals, but the specific enzymes responsible for this bioactivation event in vivo have not been identified. We tested the hypothesis that lung P450 oxidoreductase (POR or CPR) is important in PQ-induced lung fibrosis in mice. A lung-Cpr-null mouse model was utilized, which undergoes doxycycline-induced, Cre recombinase-mediated deletion of the Por gene specifically in airway Club cells and alveolar type 2 cells in the lung. The lungs of lung-Cpr-null mice and their wild-type littermates were collected on day 15 after a single intraperitoneal injection of saline (control) or PQ (20 mg/kg). Lung tissue sections were stained with picrosirius red for detection of collagen fibrils. Fibrotic lung areas were found to be significantly smaller (1.6-fold for males and 1.4-fold for females) in PQ-treated lung-Cpr-null mice than in sex- and treatment-matched wild-type mice. The levels of collagen in lung tissue homogenate were also lower (1.4–2.3-fold; p < 0.05) in PQ-treated lung-Cpr-null mice compared to PQ-treated wild-type mice. In contrast, plasma PQ toxicokinetic profiles were not different between sex-matched wild-type and lung-Cpr-null mice. Taken together, these results indicate that lung POR plays an important role in PQ-induced pulmonary fibrosis. MDPI 2022-01-24 /pmc/articles/PMC8868258/ /pubmed/35204102 http://dx.doi.org/10.3390/antiox11020219 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kovalchuk, Nataliia Jilek, Joseph L. Van Winkle, Laura S. Cherrington, Nathan J. Ding, Xinxin Role of Lung P450 Oxidoreductase in Paraquat-Induced Collagen Deposition in the Lung |
title | Role of Lung P450 Oxidoreductase in Paraquat-Induced Collagen Deposition in the Lung |
title_full | Role of Lung P450 Oxidoreductase in Paraquat-Induced Collagen Deposition in the Lung |
title_fullStr | Role of Lung P450 Oxidoreductase in Paraquat-Induced Collagen Deposition in the Lung |
title_full_unstemmed | Role of Lung P450 Oxidoreductase in Paraquat-Induced Collagen Deposition in the Lung |
title_short | Role of Lung P450 Oxidoreductase in Paraquat-Induced Collagen Deposition in the Lung |
title_sort | role of lung p450 oxidoreductase in paraquat-induced collagen deposition in the lung |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8868258/ https://www.ncbi.nlm.nih.gov/pubmed/35204102 http://dx.doi.org/10.3390/antiox11020219 |
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