From preclinical to clinical models of acute respiratory distress syndrome

Zhai, Ruoyang; Bonda, Woodys Lenga Ma; Matute-Bello, Gustavo; Jabaudon, Matthieu

doi:10.22514/sv.2021.228

Cited by 3 publications

(3 citation statements)

References 103 publications

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“…Our study also has several strengths. We used a mouse model of direct lung epithelial injury over multiple days [ 27 , 30 , 31 ] and an in vitro model of alveolar epithelial injury [ 34 , 47 ], which are validated and have translational value. In addition, the sevoflurane concentrations used in our study are similar to those used in clinical practice for deep sedation, which is often required in the early management of clinical ARDS [ 12 , 48 ], and in a large multicenter clinical trial [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of sevoflurane on lung epithelial permeability in experimental models of acute respiratory distress syndrome

et al. 2023

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Background Preclinical studies in acute respiratory distress syndrome (ARDS) have suggested that inhaled sevoflurane may have lung-protective effects and clinical trials are ongoing to assess its impact on major clinical outcomes in patients with ARDS. However, the underlying mechanisms of these potential benefits are largely unknown. This investigation focused on the effects of sevoflurane on lung permeability changes after sterile injury and the possible associated mechanisms. Methods To investigate whether sevoflurane could decrease lung alveolar epithelial permeability through the Ras homolog family member A (RhoA)/phospho-Myosin Light Chain 2 (Ser19) (pMLC)/filamentous (F)-actin pathway and whether the receptor for advanced glycation end-products (RAGE) may mediate these effects. Lung permeability was assessed in RAGE−/− and littermate wild-type C57BL/6JRj mice on days 0, 1, 2, and 4 after acid injury, alone or followed by exposure at 1% sevoflurane. Cell permeability of mouse lung epithelial cells was assessed after treatment with cytomix (a mixture of TNFɑ, IL-1β, and IFNγ) and/or RAGE antagonist peptide (RAP), alone or followed by exposure at 1% sevoflurane. Levels of zonula occludens-1, E-cadherin, and pMLC were quantified, along with F-actin immunostaining, in both models. RhoA activity was assessed in vitro. Results In mice after acid injury, sevoflurane was associated with better arterial oxygenation, decreased alveolar inflammation and histological damage, and non-significantly attenuated the increase in lung permeability. Preserved protein expression of zonula occludens-1 and less increase of pMLC and actin cytoskeletal rearrangement were observed in injured mice treated with sevoflurane. In vitro, sevoflurane markedly decreased electrical resistance and cytokine release of MLE-12 cells, which was associated with higher protein expression of zonula occludens-1. Improved oxygenation levels and attenuated increase in lung permeability and inflammatory response were observed in RAGE−/− mice compared to wild-type mice, but RAGE deletion did not influence the effects of sevoflurane on permeability indices after injury. However, the beneficial effect of sevoflurane previously observed in wild-type mice on day 1 after injury in terms of higher PaO2/FiO2 and decreased alveolar levels of cytokines was not found in RAGE−/− mice. In vitro, RAP alleviated some of the beneficial effects of sevoflurane on electrical resistance and cytoskeletal rearrangement, which was associated with decreased cytomix-induced RhoA activity. Conclusions Sevoflurane decreased injury and restored epithelial barrier function in two in vivo and in vitro models of sterile lung injury, which was associated with increased expression of junction proteins and decreased actin cytoskeletal rearrangement. In vitro findings suggest that sevoflurane may decrease lung epithelial permeability through the RhoA/pMLC/F-actin pathway. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Effects of sevoflurane on lung epithelial permeability in experimental models of acute respiratory distress syndrome

et al. 2023

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“…It is well known that cough in healthy individuals is a physiological defense mechanism to clear the airways of foreign particles and excessive bronchial secretions, and is a common symptom of several respiratory diseases [ 1 ]. Chronic cough can be debilitating, as the resulting distress can significantly impair the quality of life of patients [ 2 , 3 ]. Although most cases of cough are associated with infection, diagnostic tests for cough are made difficult by the long list of differential diagnoses.…”

Section: Introductionmentioning

confidence: 99%

Pectolinarigenin ameliorated airway inflammation and airway remodeling to exhibit antitussive effect

He,

Liu,

et al. 2024

Korean J Physiol Pharmacol

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Cough is a common symptom of several respiratory diseases. However, frequent coughing from acute to chronic often causes great pain to patients. It may turn into cough variant asthma, which seriously affects people's quality of life. For cough treatment, it is dominated by over-the-counter antitussive drugs, such as asmeton, but most currently available antitussive drugs have serious side effects. Thus, there is a great need for the development of new drugs with potent cough suppressant. BALB/c mice were used to construct mice model with cough to investigate the pharmacological effects of pectolinarigenin (PEC). Hematoxylin-eosin and Masson staining were used to assess lung injury and airway remodeling, and ELISA was used to assess the level of inflammatory factor release. In addition, inflammatory cell counts were measured to assess airway inflammation. Airway hyperresponsiveness assay was used to assess respiratory resistance in mice. Finally, we used Western blotting to explore the potential mechanisms of PEC. We found that PEC could alleviate lung tissue injury and reduce the release of inflammatory factors, inhibit of cough frequency and airway wall collagen deposition in mice model with cough. Meanwhile, PEC inhibited the Ras/ERK/c-Fos pathway to exhibit antitussive effect. Therefore, PEC may be a potential drug for cough suppression.

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“…Acute lung injury (ALI) is regarded as a critically grievous clinical syndrome characterized by increasing capillary permeability, release of inflammatory cytokines, and accumulation of neutrophils in the lungs. 1,2 Many precipitating factors, such as inflammation of the lungs, space-occupying lesions and trauma, etc., and ultimately lead to acute hypoxic respiratory insufficiency or respiratory failure, even acute respiratory distress syndrome (ARDS). 3 Therefore, ALI is a typical clinical disease with high morbidity and mortality rates.…”

Section: Introductionmentioning

confidence: 99%

Identification of biomarkers and candidate small-molecule drugs in lipopolysaccharide (LPS)-induced acute lung injury by bioinformatics analysis

Wang

Chen

2023

Allergol Immunopathol

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Background/objective: Acute lung injury (ALI) is a critical clinical syndrome with high rates of incidence and mortality. However, its molecular mechanism remains unclear. The current work aimed to explore the molecular mechanisms of ALI by identifying different expression genes (DEGs) and candidate drugs using a combination of chip analysis and experimental validation. Methods: Three microarray datasets were downloaded from Gene Expression Omnibus (GEO) database to obtain DEGs. We conducted a Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway-enrichment analyses of overlapping DEGs among three databases. The expression level of key gene was verified by Western blotting analysis in LPS-treated ALI cell models. Finally, we predicted the candidate drugs targeting the key gene that might be effective for ALI treatment, and the role of candidate drug in treating ALI was verified by investigation. Results: A total 29 overlapping DEGs were up-regulated in LPS-induced ALI groups. They were enriched in inflammation and inflammation-related pathways. Serpin family A member 3 (SERPINA3) was defined as a key gene because it was associated with inflammation pathway and up-regulated in microarray datasets in LPS-induced ALI. In LPS-induced human bronchial epithelial cells transformed with Ad12-SV40-2B (BEAS-2B) cells, SERPINA3 was enhanced. Pyridoxal phosphate as an upstream drug of SERPINA3 could improve cell viability and reduce expression inflammatory factors in LPS-treated BEAS-2B cells. Conclusion: Our study suggested that pyridoxal phosphate could be a candidate drug targeting SERPINA3 gene in LPS-induced ALI. It has protective and anti-inflammatory effects in BEAS-2B cells, and may become a potential novel treatment for ALI.

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From preclinical to clinical models of acute respiratory distress syndrome

Cited by 3 publications

References 103 publications

Effects of sevoflurane on lung epithelial permeability in experimental models of acute respiratory distress syndrome

Effects of sevoflurane on lung epithelial permeability in experimental models of acute respiratory distress syndrome

Pectolinarigenin ameliorated airway inflammation and airway remodeling to exhibit antitussive effect

Identification of biomarkers and candidate small-molecule drugs in lipopolysaccharide (LPS)-induced acute lung injury by bioinformatics analysis

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