scholarly journals Colchicine reduces lung injury in experimental acute respiratory distress syndrome

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0242318
Author(s):  
Jocelyn Dupuis ◽  
Martin G. Sirois ◽  
Eric Rhéaume ◽  
Quang T. Nguyen ◽  
Marie-Élaine Clavet-Lanthier ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Oleic Acid ◽  
Respiratory Failure ◽  
Lung Injury ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Respiratory Acidosis ◽  
Neutrophil Recruitment ◽  
Cell Surface Expression

The acute respiratory distress syndrome (ARDS) is characterized by intense dysregulated inflammation leading to acute lung injury (ALI) and respiratory failure. There are no effective pharmacologic therapies for ARDS. Colchicine is a low-cost, widely available drug, effective in the treatment of inflammatory conditions. We studied the effects of colchicine pre-treatment on oleic acid-induced ARDS in rats. Rats were treated with colchicine (1 mg/kg) or placebo for three days prior to intravenous oleic acid-induced ALI (150 mg/kg). Four hours later they were studied and compared to a sham group. Colchicine reduced the area of histological lung injury by 61%, reduced lung edema, and markedly improved oxygenation by increasing PaO2/FiO2 from 66 ± 13 mmHg (mean ± SEM) to 246 ± 45 mmHg compared to 380 ± 18 mmHg in sham animals. Colchicine also reduced PaCO2 and respiratory acidosis. Lung neutrophil recruitment, assessed by myeloperoxidase immunostaining, was greatly increased after injury from 1.16 ± 0.19% to 8.86 ± 0.66% and significantly reduced by colchicine to 5.95 ± 1.13%. Increased lung NETosis was also reduced by therapy. Circulating leukocytosis after ALI was not reduced by colchicine therapy, but neutrophils reactivity and CD4 and CD8 cell surface expression on lymphocyte populations were restored. Colchicine reduces ALI and respiratory failure in experimental ARDS in relation with reduced lung neutrophil recruitment and reduced circulating leukocyte activation. This study supports the clinical development of colchicine for the prevention of ARDS in conditions causing ALI.

scholarly journals Oleic acid-based nanosystems for mitigating acute respiratory distress syndrome in mice through neutrophil suppression: how the particulate size affects therapeutic efficiency

2020 ◽  
Author(s):  
Huang-Ping Yu ◽  
Fu-Chao Liu ◽  
Ani Umoro ◽  
Zih-Chan Lin ◽  
Ahmed O. Elzoghby ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Oleic Acid ◽  
Lung Injury ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Inflammatory Activity ◽  
Human Neutrophils ◽  
Essential Property ◽  
Anti Inflammatory

Abstract Background: Oleic acid (OA) is reported to show anti-inflammatory activity toward activated neutrophils. It is also an important material in nanoparticles for increased stability and cellular internalization. We aimed to evaluate the anti-inflammatory activity of injectable OA-based nanoparticles for treating lung injury. Different sizes of nanocarriers were prepared to explore the effect of nanoparticulate size on inflammation inhibition. Results: The nanoparticles were fabricated with the mean diameters of 105, 153, and 225 nm. The nanocarriers were ingested by isolated human neutrophils during a 5-min period, with the smaller sizes exhibiting greater uptake. The size reduction led to the decrease of cell viability and the intracellular calcium level. The OA-loaded nanosystems dose-dependently suppressed the superoxide anion and elastase produced by the stimulated neutrophils. The inhibition level was comparable for the nanoparticles of different sizes. In the ex vivo biodistribution study, the pulmonary accumulation of nanoparticles increased following the increase of particle size. The nanocarriers were mainly excreted by the liver and bile clearance. Mice were exposed to intratracheal lipopolysaccharide (LPS) to induce acute respiratory distress syndrome (ARDS), like lung damage. The lipid-based nanocarriers mitigated myeloperoxidase (MPO) and cytokines more effectively as compared to OA solution. The larger nanoparticles displayed greater reduction on MPO, TNF-α, and IL-6 than the smaller ones. The histology confirmed the decreased pulmonary neutrophil recruitment and lung-architecture damage after intravenous administration of larger nanoparticles. Conclusions: Nanoparticulate size, an essential property governing the anti-inflammatory effect and lung-injury therapy, had different effects on activated neutrophil inhibition and in vivo therapeutic efficacy.

scholarly journals Acute Respiratory Distress Syndrome: Role of Oleic Acid-Triggered Lung Injury and Inflammation

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Cassiano Felippe Gonçalves-de-Albuquerque ◽  
Adriana Ribeiro Silva ◽  
Patrícia Burth ◽  
Mauro Velho Castro-Faria ◽  
Hugo Caire Castro-Faria-Neto
Keyword(s):  
Fatty Acids ◽  
Acute Respiratory Distress Syndrome ◽  
Oleic Acid ◽  
Lung Injury ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Inflammatory Diseases ◽  
Edema Formation

Lung injury especially acute respiratory distress syndrome (ARDS) can be triggered by diverse stimuli, including fatty acids and microbes. ARDS affects thousands of people worldwide each year, presenting high mortality rate and having an economic impact. One of the hallmarks of lung injury is edema formation with alveoli flooding. Animal models are used to study lung injury. Oleic acid-induced lung injury is a widely used model resembling the human disease. The oleic acid has been linked to metabolic and inflammatory diseases; here we focus on lung injury. Firstly, we briefly discuss ARDS and secondly we address the mechanisms by which oleic acid triggers lung injury and inflammation.

Assessment of Acute Respiratory Failure

2018 ◽  
Author(s):  
Nathan R. Manley ◽  
Martin A Croce
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Respiratory Failure ◽  
Lung Injury ◽  
Acute Respiratory Failure ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Medical Decision ◽  
Surgical Patient ◽  
Respiratory Drive

Acute respiratory failure (ARF) is fundamentally a dysfunction of gas exchange and can be due to either inadequate carbon dioxide elimination causing hypercapnia or poor oxygen exchange and delivery causing hypoxemia. A variety of etiologies exist that cause ARF in the surgical patient, including previous lung disease, such as chronic obstructive pulmonary disease or asthma, neurologic compromise of respiratory drive, nutritional and metabolic derangements that can alter respiratory metabolism and mechanics, direct lung injury, and infection. The type of surgery and the time since surgery are other key factors that influence medical decision making and that will influence priorities in the assessment and management of ARF. This review explores the full spectrum of ARF in the surgical patient, focusing particularly on its assessment and initial management. Figures illustrate algorithms in the approach to the surgical patient with ARF and show example radiographic images of acute respiratory distress syndrome (ARDS), a common complication. Tables summarize indications for emergent intubation, key etiologies of ARF, and the evolving definitions of acute lung injury and ARDS. Key words: acute respiratory distress syndrome, acute respiratory failure, hypercapnia, hypoxemia, mechanical ventilation 

scholarly journals Oleic acid-based nanosystems for mitigating acute respiratory distress syndrome in mice through neutrophil suppression: how the particulate size affects therapeutic efficiency

2019 ◽  
Author(s):  
Jia-You Fang ◽  
Huang-Ping Yu ◽  
Fu-Chao Liu ◽  
Ani Umoro ◽  
Zih-Chan Lin ◽  
...  
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Oleic Acid ◽  
Lung Injury ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Inflammatory Activity ◽  
Human Neutrophils ◽  
Anti Inflammatory

Abstract Background: Oleic acid (OA) is reported to show anti-inflammatory activity toward activated neutrophils. It is also an important material in nanoparticles for increased stability and cellular internalization. We aimed to evaluate the anti-inflammatory activity of injectable OA-based nanoparticles for treating lung injury. Different sizes of nanocarriers were prepared to explore the effect of nanoparticulate size on inflammation inhibition. Results: The nanoparticles were fabricated with the mean diameters of 105, 153, and 225 nm. The nanocarriers were ingested by isolated human neutrophils during a 5-min period, with the smaller sizes exhibiting greater uptake. The size reduction led to the decrease of cell viability and the intracellular calcium level. The OA-loaded nanosystems dose-dependently suppressed the superoxide anion and elastase produced by the stimulated neutrophils. The inhibition level was comparable for the nanoparticles of different sizes. In the in vivo biodistribution study, the pulmonary accumulation of nanoparticles increased following the increase of particle size. The nanocarriers were mainly excreted by the liver and bile clearance. Mice were exposed to intratracheal lipopolysaccharide (LPS) to induce acute respiratory distress syndrome (ARDS), like lung damage. The lipid-based nanocarriers mitigated myeloperoxidase (MPO) and cytokines more effectively as compared to OA solution. The larger nanoparticles displayed greater reduction on MPO, TNF-α, and IL-6 than the smaller ones. The histology confirmed the decreased pulmonary neutrophil recruitment and lung-architecture damage after intravenous administration of larger nanoparticles. Conclusions: Nanoparticulate size, an essential property governing the anti-inflammatory effect and lung-injury therapy, had different effects on activated neutrophil inhibition and in vivo therapeutic efficacy.

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