scholarly journals An Experimental Model of Direct Acute Lung Injury in Rats Caused by Intratracheal Administration of Lipopolysaccharide from Salmonella enterica

Biomeditsina ◽  
2021 ◽  
Vol 17 (3) ◽  
pp. 84-89
Author(s):  
V. A. Pugach ◽  
M. A. Tyunin ◽  
N. S. Ilinskiy ◽  
E. V. Levchuk ◽  
E. I. Strokina ◽  
...  
Keyword(s):  
Body Weight ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Experimental Model ◽  
Lung Tissue ◽  
Salmonella Enterica ◽  
Distress Syndrome ◽  
Preclinical Research ◽  
Intratracheal Administration ◽  
Selection Of

An experimental model of direct acute lung injury was developed by intratracheal administration of lipopolysaccharide from Salmonella enterica (LD50 = 20 mg/kg). The dynamics of animal lethality, body weight, temperature and the severity of pathomorphological changes in the lung tissue were analyzed. It was found that the developed model is accompanied by a progressive decrease in body weight by 15%, persistent hypothermic reaction, pronounced edema and inflammatory reaction in the lung tissue within 4 days following lipopolysaccharide administration. The simplicity and reproducibility of the developed experimental model make it useful for preclinical research aimed at selection of candidate drugs for the prevention and treatment of acute respiratory distress syndrome.

scholarly journals A Model of Fatal Acute Lung Injury and Acute Respiratory Distress Syndrome

Biomeditsina ◽  
2020 ◽  
Vol 16 (4) ◽  
pp. 24-33
Author(s):  
I. A. Pomytkin ◽  
V. N. Karkischenko ◽  
Yu. V. Fokin ◽  
M. S. Nesterov ◽  
N. V. Petrova
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Diffuse Alveolar Damage ◽  
Mrna Level ◽  
Intratracheal Administration ◽  
Drug Candidates

This study was aimed at developing an experimental model of fatal acute lung injury and acute respiratory distress syndrome (ARDS) based on the intratracheal administration of bacterial lipopolysaccharide (LPS) in combination with muramylpeptide and Freund’s complete adjuvant to C57Bl/6Y mice sensitized with α-galactosylceramide. The developed model is characterized by diffuse alveolar damage to the lungs and high mortality rates, as well as by a multifold increase in the mRNA level of interleukin-6 in the lungs. The model can be used for assessing the efficacy of drug candidates in the treatment of acute lung injury and ARDS, including in COVID-19.

scholarly journals Prevention of LPS-Induced Acute Lung Injury in Mice by Progranulin

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Zhongliang Guo ◽  
Qinchuan Li ◽  
Yang Han ◽  
Yongjie Liang ◽  
Zengguang Xu ◽  
...  
Keyword(s):  
Body Weight ◽  
Acute Respiratory Distress Syndrome ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Respiratory Distress Syndrome ◽  
Distress Syndrome ◽  
Pulmonary Inflammation ◽  
Therapeutic Strategies ◽  
Total Cell ◽  
The Body

The acute respiratory distress syndrome (ARDS), a clinical complication of severe acute lung injury (ALI) in humans, is a leading cause of morbidity and mortality in critically ill patients. Despite decades of research, few therapeutic strategies for clinical ARDS have emerged. Here we carefully evaluated the effect of progranulin (PGRN) in treatment of ARDS using the murine model of lipopolysaccharide (LPS)-induced ALI. We reported that administration of PGRN maintained the body weight and survival of ALI mice. We revealed that administration of PGRN significantly reduced LPS-induced pulmonary inflammation, as reflected by reductions in total cell and neutrophil counts, proinflammatory cytokines, as well as chemokines in bronchoalveolar lavage (BAL) fluid. Furthermore, administration of PGRN resulted in remarkable reversal of LPS-induced increases in lung permeability as assessed by reductions in total protein, albumin, and IgM in BAL fluid. Consistently, we revealed a significant reduction of histopathology changes of lung in mice received PGRN treatment. Finally, we showed that PGRN/TNFR2 interaction was crucial for the protective effect of PGRN on the LPS-induced ALI. Our findings strongly demonstrated that PGRN could effectively ameliorate the LPS-induced ALI in mice, suggesting a potential application for PGRN-based therapy to treat clinical ARDS.

Endotoxin-induced acute lung injury requires interaction with the liver

2005 ◽  
Vol 289 (5) ◽  
pp. L769-L776 ◽  
Author(s):  
Amsel M. Siore ◽  
Richard E. Parker ◽  
Arlene A. Stecenko ◽  
Chris Cuppels ◽  
Martha McKean ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Lung Tissue ◽  
Distress Syndrome ◽  
Laboratory Data ◽  
Lung Edema ◽  
Direct Effects ◽  
Tnf Α ◽  
Severe Lung

Clinical and laboratory data indicate that the liver plays an important role in the incidence, pathogenesis, and outcome of acute lung injury/acute respiratory distress syndrome. To distinguish direct effects of endotoxin on the lungs from liver-dependent effects during the early phase of the response to endotoxemia, we used an in situ perfused piglet preparation in which only the ventilated lung or both the lung and liver could be included in a blood perfused circuit. We monitored pulmonary vascular resistance, oxygenation, neutrophil count, lung edema as reflected by wet-dry weights of lung tissue, perfusate concentrations of TNF-α, IL-6, and 8-isoprostane (a marker of oxidative stress), and activation of the transcription factor (NF-κB) in lung tissue before and for 2 h after endotoxin. When only the lung was perfused, endotoxin caused pulmonary hypertension and neutropenia; but oxygenation was maintained; TNF-α, IL-6, and 8-isoprostane levels were minimally elevated; and there was no lung edema. When both the liver and lung were perfused, endotoxin caused marked hypoxemia, large increases in perfusate TNF-α, IL-6, and 8-isoprostane concentrations, and severe lung edema. NF-κB activation in the lung was greatest when the liver was in the perfusion circuit. We conclude that the direct effects of endotoxemia on the lungs include vasoconstriction and leukocyte sequestration, but not lung injury. Intense activation of the inflammatory response and oxidative injury that results in pulmonary edema and hypoxemia (acute lung injury) requires interaction of the lungs with the liver.

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