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Efficacy of Inhaled N-Chlorotaurine in a Mouse Model of Lichtheimia corymbifera and Aspergillus fumigatus Pneumonia

N-chlorotaurine (NCT) can be used topically as a well-tolerated anti-infective at different body sites. The aim of this study was to investigate the efficacy of inhaled NCT in a mouse model of fungal pneumonia. Specific pathogen-free female C57BL/6JRj seven-week-old mice were immune-suppressed with...

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Autores principales: Speth, Cornelia, Rambach, Günter, Windisch, Andrea, Neurauter, Magdalena, Maier, Hans, Nagl, Markus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9143854/
https://www.ncbi.nlm.nih.gov/pubmed/35628790
http://dx.doi.org/10.3390/jof8050535
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author Speth, Cornelia
Rambach, Günter
Windisch, Andrea
Neurauter, Magdalena
Maier, Hans
Nagl, Markus
author_facet Speth, Cornelia
Rambach, Günter
Windisch, Andrea
Neurauter, Magdalena
Maier, Hans
Nagl, Markus
author_sort Speth, Cornelia
collection PubMed
description N-chlorotaurine (NCT) can be used topically as a well-tolerated anti-infective at different body sites. The aim of this study was to investigate the efficacy of inhaled NCT in a mouse model of fungal pneumonia. Specific pathogen-free female C57BL/6JRj seven-week-old mice were immune-suppressed with cyclophosphamide. After 4 days, the mice were inoculated intranasally with 1.5 × 10E7 spores of Lichtheimia corymbifera or 1.0 × 10E7 spores of Aspergillus fumigatus. They were randomized and treated three times daily for 10 min with aerosolized 1% NCT or 0.9% sodium chloride starting 1 h after the inoculation. The mice were observed for survival for two weeks, and fungal load, blood inflammation parameters, bronchoalveolar lavage, and histology of organs were evaluated upon their death or at the end of this period. Inhalations were well-tolerated. After challenge with L. corymbifera, seven out of the nine mice (77.8%) survived for 15 days in the test group, which was in strong contrast to one out of the nine mice (11.1%) in the control group (p = 0.0049). The count of colony-forming units in the homogenized lung tissues came to 1.60 (1.30; 1.99; median, quartiles) log(10) in the test group and to 4.26 (2.17; 4.53) log(10) in the control group (p = 0.0032). Body weight and temperature, white blood count, and haptoglobin significantly improved with NCT treatment. With A. fumigatus, all the mice except for one in the test group died within 4 days without a significant difference from the control group. Inhaled NCT applied early demonstrated a highly significant curative effect in L. corymbifera pneumonia, while this could not be shown in A. fumigatus pneumonia, probably due to a too high inoculum. Nevertheless, this study for the first time disclosed efficacy of NCT in pneumonia in vivo.
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spelling pubmed-91438542022-05-29 Efficacy of Inhaled N-Chlorotaurine in a Mouse Model of Lichtheimia corymbifera and Aspergillus fumigatus Pneumonia Speth, Cornelia Rambach, Günter Windisch, Andrea Neurauter, Magdalena Maier, Hans Nagl, Markus J Fungi (Basel) Article N-chlorotaurine (NCT) can be used topically as a well-tolerated anti-infective at different body sites. The aim of this study was to investigate the efficacy of inhaled NCT in a mouse model of fungal pneumonia. Specific pathogen-free female C57BL/6JRj seven-week-old mice were immune-suppressed with cyclophosphamide. After 4 days, the mice were inoculated intranasally with 1.5 × 10E7 spores of Lichtheimia corymbifera or 1.0 × 10E7 spores of Aspergillus fumigatus. They were randomized and treated three times daily for 10 min with aerosolized 1% NCT or 0.9% sodium chloride starting 1 h after the inoculation. The mice were observed for survival for two weeks, and fungal load, blood inflammation parameters, bronchoalveolar lavage, and histology of organs were evaluated upon their death or at the end of this period. Inhalations were well-tolerated. After challenge with L. corymbifera, seven out of the nine mice (77.8%) survived for 15 days in the test group, which was in strong contrast to one out of the nine mice (11.1%) in the control group (p = 0.0049). The count of colony-forming units in the homogenized lung tissues came to 1.60 (1.30; 1.99; median, quartiles) log(10) in the test group and to 4.26 (2.17; 4.53) log(10) in the control group (p = 0.0032). Body weight and temperature, white blood count, and haptoglobin significantly improved with NCT treatment. With A. fumigatus, all the mice except for one in the test group died within 4 days without a significant difference from the control group. Inhaled NCT applied early demonstrated a highly significant curative effect in L. corymbifera pneumonia, while this could not be shown in A. fumigatus pneumonia, probably due to a too high inoculum. Nevertheless, this study for the first time disclosed efficacy of NCT in pneumonia in vivo. MDPI 2022-05-20 /pmc/articles/PMC9143854/ /pubmed/35628790 http://dx.doi.org/10.3390/jof8050535 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
Speth, Cornelia
Rambach, Günter
Windisch, Andrea
Neurauter, Magdalena
Maier, Hans
Nagl, Markus
Efficacy of Inhaled N-Chlorotaurine in a Mouse Model of Lichtheimia corymbifera and Aspergillus fumigatus Pneumonia
title Efficacy of Inhaled N-Chlorotaurine in a Mouse Model of Lichtheimia corymbifera and Aspergillus fumigatus Pneumonia
title_full Efficacy of Inhaled N-Chlorotaurine in a Mouse Model of Lichtheimia corymbifera and Aspergillus fumigatus Pneumonia
title_fullStr Efficacy of Inhaled N-Chlorotaurine in a Mouse Model of Lichtheimia corymbifera and Aspergillus fumigatus Pneumonia
title_full_unstemmed Efficacy of Inhaled N-Chlorotaurine in a Mouse Model of Lichtheimia corymbifera and Aspergillus fumigatus Pneumonia
title_short Efficacy of Inhaled N-Chlorotaurine in a Mouse Model of Lichtheimia corymbifera and Aspergillus fumigatus Pneumonia
title_sort efficacy of inhaled n-chlorotaurine in a mouse model of lichtheimia corymbifera and aspergillus fumigatus pneumonia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9143854/
https://www.ncbi.nlm.nih.gov/pubmed/35628790
http://dx.doi.org/10.3390/jof8050535
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