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Alcohol Worsens Acute Lung Injury by Inhibiting Alveolar Sodium Transport through the Adenosine A1 Receptor

OBJECTIVE: Alcohol intake increases the risk of acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) and is associated with poor outcomes in patients who develop these syndromes. No specific therapies are currently available to treat or decrease the risk of ARDS in patients wit...

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Autores principales: Dada, Laura, Gonzalez, Angel R., Urich, Daniela, Soberanes, Saul, Manghi, Tomas S., Chiarella, Sergio E., Chandel, Navdeep S., Budinger, G. R. Scott, Mutlu, Gökhan M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3260305/
https://www.ncbi.nlm.nih.gov/pubmed/22272351
http://dx.doi.org/10.1371/journal.pone.0030448
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author Dada, Laura
Gonzalez, Angel R.
Urich, Daniela
Soberanes, Saul
Manghi, Tomas S.
Chiarella, Sergio E.
Chandel, Navdeep S.
Budinger, G. R. Scott
Mutlu, Gökhan M.
author_facet Dada, Laura
Gonzalez, Angel R.
Urich, Daniela
Soberanes, Saul
Manghi, Tomas S.
Chiarella, Sergio E.
Chandel, Navdeep S.
Budinger, G. R. Scott
Mutlu, Gökhan M.
author_sort Dada, Laura
collection PubMed
description OBJECTIVE: Alcohol intake increases the risk of acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) and is associated with poor outcomes in patients who develop these syndromes. No specific therapies are currently available to treat or decrease the risk of ARDS in patients with alcoholism. We have recently shown increased levels of lung adenosine inhibit alveolar fluid clearance, an important predictor of outcome in patients with ARDS. We hypothesized that alcohol might worsen lung injury by increasing lung adenosine levels, resulting in impaired active Na(+) transport in the lung. METHODS: We treated wild-type mice with alcohol administered i.p. to achieve blood alcohol levels associated with moderate to severe intoxication and measured the rate of alveolar fluid clearance and Na,K-ATPase expression in peripheral lung tissue and assessed the effect of alcohol on survival during exposure to hyperoxia. We used primary rat alveolar type II cells to investigate the mechanisms by which alcohol regulates alveolar Na(+) transport. RESULTS: Exposure to alcohol reduced alveolar fluid clearance, downregulated Na,K-ATPase in the lung tissue and worsened hyperoxia-induced lung injury. Alcohol caused an increase in BAL fluid adenosine levels. A similar increase in lung adenosine levels was observed after exposure to hyperoxia. In primary rat alveolar type II cells alcohol and adenosine decreased the abundance of the Na,K-ATPase at the basolateral membrane via a mechanism that required activation of the AMPK. CONCLUSIONS: Alcohol decreases alveolar fluid clearance and impairs survival from acute lung injury. Alcohol induced increases in lung adenosine levels may be responsible for reduction in alveolar fluid clearance and associated worsening of lung injury.
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spelling pubmed-32603052012-01-23 Alcohol Worsens Acute Lung Injury by Inhibiting Alveolar Sodium Transport through the Adenosine A1 Receptor Dada, Laura Gonzalez, Angel R. Urich, Daniela Soberanes, Saul Manghi, Tomas S. Chiarella, Sergio E. Chandel, Navdeep S. Budinger, G. R. Scott Mutlu, Gökhan M. PLoS One Research Article OBJECTIVE: Alcohol intake increases the risk of acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) and is associated with poor outcomes in patients who develop these syndromes. No specific therapies are currently available to treat or decrease the risk of ARDS in patients with alcoholism. We have recently shown increased levels of lung adenosine inhibit alveolar fluid clearance, an important predictor of outcome in patients with ARDS. We hypothesized that alcohol might worsen lung injury by increasing lung adenosine levels, resulting in impaired active Na(+) transport in the lung. METHODS: We treated wild-type mice with alcohol administered i.p. to achieve blood alcohol levels associated with moderate to severe intoxication and measured the rate of alveolar fluid clearance and Na,K-ATPase expression in peripheral lung tissue and assessed the effect of alcohol on survival during exposure to hyperoxia. We used primary rat alveolar type II cells to investigate the mechanisms by which alcohol regulates alveolar Na(+) transport. RESULTS: Exposure to alcohol reduced alveolar fluid clearance, downregulated Na,K-ATPase in the lung tissue and worsened hyperoxia-induced lung injury. Alcohol caused an increase in BAL fluid adenosine levels. A similar increase in lung adenosine levels was observed after exposure to hyperoxia. In primary rat alveolar type II cells alcohol and adenosine decreased the abundance of the Na,K-ATPase at the basolateral membrane via a mechanism that required activation of the AMPK. CONCLUSIONS: Alcohol decreases alveolar fluid clearance and impairs survival from acute lung injury. Alcohol induced increases in lung adenosine levels may be responsible for reduction in alveolar fluid clearance and associated worsening of lung injury. Public Library of Science 2012-01-17 /pmc/articles/PMC3260305/ /pubmed/22272351 http://dx.doi.org/10.1371/journal.pone.0030448 Text en This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
Dada, Laura
Gonzalez, Angel R.
Urich, Daniela
Soberanes, Saul
Manghi, Tomas S.
Chiarella, Sergio E.
Chandel, Navdeep S.
Budinger, G. R. Scott
Mutlu, Gökhan M.
Alcohol Worsens Acute Lung Injury by Inhibiting Alveolar Sodium Transport through the Adenosine A1 Receptor
title Alcohol Worsens Acute Lung Injury by Inhibiting Alveolar Sodium Transport through the Adenosine A1 Receptor
title_full Alcohol Worsens Acute Lung Injury by Inhibiting Alveolar Sodium Transport through the Adenosine A1 Receptor
title_fullStr Alcohol Worsens Acute Lung Injury by Inhibiting Alveolar Sodium Transport through the Adenosine A1 Receptor
title_full_unstemmed Alcohol Worsens Acute Lung Injury by Inhibiting Alveolar Sodium Transport through the Adenosine A1 Receptor
title_short Alcohol Worsens Acute Lung Injury by Inhibiting Alveolar Sodium Transport through the Adenosine A1 Receptor
title_sort alcohol worsens acute lung injury by inhibiting alveolar sodium transport through the adenosine a1 receptor
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3260305/
https://www.ncbi.nlm.nih.gov/pubmed/22272351
http://dx.doi.org/10.1371/journal.pone.0030448
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