Polyvinylalcohol-carbazate mitigates acute lung injury caused by hydrochloric acid

BackgroundAcute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are important causes of morbidity and mortality in critically ill patients. Gastric contents aspiration is one of the most common causes of ALI/ARDS. To date, there are still no specific and effective pharmacological tr...

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Main Authors: Caijuan Dong, Jielu Liu, Alessandro Quaranta, Xu Jing, Mu Nie, Craig E. Wheelock, Benjamin Murrell, Jonathan M. Coquet, Tim Melander Bowden, Thomas Engstrand, Mikael Adner
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-11-01
Series:Frontiers in Pharmacology
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Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2024.1503648/full
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author Caijuan Dong
Caijuan Dong
Jielu Liu
Alessandro Quaranta
Xu Jing
Mu Nie
Craig E. Wheelock
Craig E. Wheelock
Benjamin Murrell
Jonathan M. Coquet
Tim Melander Bowden
Thomas Engstrand
Mikael Adner
author_facet Caijuan Dong
Caijuan Dong
Jielu Liu
Alessandro Quaranta
Xu Jing
Mu Nie
Craig E. Wheelock
Craig E. Wheelock
Benjamin Murrell
Jonathan M. Coquet
Tim Melander Bowden
Thomas Engstrand
Mikael Adner
author_sort Caijuan Dong
collection DOAJ
description BackgroundAcute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are important causes of morbidity and mortality in critically ill patients. Gastric contents aspiration is one of the most common causes of ALI/ARDS. To date, there are still no specific and effective pharmacological treatments for ALI/ARDS. Polyvinylalcohol-carbazate (PVAC), a polymer that can bind endogenous aldehydes, neutralize oxidative stress and inhibit inflammatory factors, may be a potential treatment for ALI/ARDS.MethodsA hydrochloric acid (HCl) induced mouse model was employed to assess the effect of PVAC. The changes of lung mechanics, pulmonary edema, histology and immune cells, cytokines, and lipid mediators in bronchioalveolar lavage fluid (BALF) were investigated in HCl-challenged mice.ResultsIn the HCl model, PVAC administration alleviated airway hyperresponsiveness and improved pulmonary edema and damage. In addition, it decreased the recruitment of neutrophils to the lung, and inhibited the increase of IL-6, TNF-α and leukotriene B4.ConclusionThese data indicates that PVAC is a potential candidate for the treatment of ALI/ARDS induced by aspiration of gastric acid or for the control of “asthma-like” symptoms in patients with gastroesophageal reflux.
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spelling doaj-art-a290dc59624043b59fa3c9ea08088dab2024-11-21T04:37:13ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122024-11-011510.3389/fphar.2024.15036481503648Polyvinylalcohol-carbazate mitigates acute lung injury caused by hydrochloric acidCaijuan Dong0Caijuan Dong1Jielu Liu2Alessandro Quaranta3Xu Jing4Mu Nie5Craig E. Wheelock6Craig E. Wheelock7Benjamin Murrell8Jonathan M. Coquet9Tim Melander Bowden10Thomas Engstrand11Mikael Adner12Experimental Asthma and Allergy Research Unit, Institute of Environmental Medicine (IMM), Karolinska Institutet, Stockholm, SwedenDepartment of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiang Su, ChinaExperimental Asthma and Allergy Research Unit, Institute of Environmental Medicine (IMM), Karolinska Institutet, Stockholm, SwedenUnit of Integrative Metabolomics, Institute of Environmental Medicine (IMM), Karolinska Institutet, Stockholm, SwedenDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, SwedenExperimental Asthma and Allergy Research Unit, Institute of Environmental Medicine (IMM), Karolinska Institutet, Stockholm, SwedenUnit of Integrative Metabolomics, Institute of Environmental Medicine (IMM), Karolinska Institutet, Stockholm, SwedenDepartment of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, SwedenDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, SwedenDepartment of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, SwedenDepartment of Chemistry-Ångström Laboratory, Uppsala University, Uppsala, SwedenDepartment of Molecular Medicine and Surgery, plastic surgery section, Karolinska University Hospital, Stockholm, SwedenExperimental Asthma and Allergy Research Unit, Institute of Environmental Medicine (IMM), Karolinska Institutet, Stockholm, SwedenBackgroundAcute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are important causes of morbidity and mortality in critically ill patients. Gastric contents aspiration is one of the most common causes of ALI/ARDS. To date, there are still no specific and effective pharmacological treatments for ALI/ARDS. Polyvinylalcohol-carbazate (PVAC), a polymer that can bind endogenous aldehydes, neutralize oxidative stress and inhibit inflammatory factors, may be a potential treatment for ALI/ARDS.MethodsA hydrochloric acid (HCl) induced mouse model was employed to assess the effect of PVAC. The changes of lung mechanics, pulmonary edema, histology and immune cells, cytokines, and lipid mediators in bronchioalveolar lavage fluid (BALF) were investigated in HCl-challenged mice.ResultsIn the HCl model, PVAC administration alleviated airway hyperresponsiveness and improved pulmonary edema and damage. In addition, it decreased the recruitment of neutrophils to the lung, and inhibited the increase of IL-6, TNF-α and leukotriene B4.ConclusionThese data indicates that PVAC is a potential candidate for the treatment of ALI/ARDS induced by aspiration of gastric acid or for the control of “asthma-like” symptoms in patients with gastroesophageal reflux.https://www.frontiersin.org/articles/10.3389/fphar.2024.1503648/fullacute respiratory distress syndromeaspiration pneumoniaoxidative stresspharmacological treatmentintranasal administration
spellingShingle Caijuan Dong
Caijuan Dong
Jielu Liu
Alessandro Quaranta
Xu Jing
Mu Nie
Craig E. Wheelock
Craig E. Wheelock
Benjamin Murrell
Jonathan M. Coquet
Tim Melander Bowden
Thomas Engstrand
Mikael Adner
Polyvinylalcohol-carbazate mitigates acute lung injury caused by hydrochloric acid
Frontiers in Pharmacology
acute respiratory distress syndrome
aspiration pneumonia
oxidative stress
pharmacological treatment
intranasal administration
title Polyvinylalcohol-carbazate mitigates acute lung injury caused by hydrochloric acid
title_full Polyvinylalcohol-carbazate mitigates acute lung injury caused by hydrochloric acid
title_fullStr Polyvinylalcohol-carbazate mitigates acute lung injury caused by hydrochloric acid
title_full_unstemmed Polyvinylalcohol-carbazate mitigates acute lung injury caused by hydrochloric acid
title_short Polyvinylalcohol-carbazate mitigates acute lung injury caused by hydrochloric acid
title_sort polyvinylalcohol carbazate mitigates acute lung injury caused by hydrochloric acid
topic acute respiratory distress syndrome
aspiration pneumonia
oxidative stress
pharmacological treatment
intranasal administration
url https://www.frontiersin.org/articles/10.3389/fphar.2024.1503648/full
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