scholarly journals MOLECULAR APOPTOSIS MECHANISMS WITH UNDERLYING EXPERIMENTAL ACUTE LUNG INJURY

2016 ◽  
Author(s):  
M. I. Marushchak ◽  
I. M. Klishch ◽  
Yu. I. Bondarenko ◽  
L. P. Mazur
Keyword(s):  
Acute Lung Injury ◽  
Hydrochloric Acid ◽  
Lung Injury ◽  
Caspase 3 ◽  
Cysteine Proteinase ◽  
Membrane Binding ◽  
Lung Homogenate ◽  
Receptor Type ◽  
Strong Positive Correlation

<p>Background. Current data suggest systemic autoimmune activation in the pathogenesis of bronchopulmonary<br />diseases. The imbalance in the system of pro- and anti-inflammatory cytokines is very important in<br />immunopathogenesis.<br />Objective. The aim of our research was to determine the caspase-3 rate in the dynamics of experimental<br />acute lung injury and to study the relationship between their level and the number of cells carrying membrane<br />binding TNF receptor type 1 to define the main mechanisms of cell death.<br />Results. The analysis of the results of caspase-3 rate in lung homogenate showed that this cysteine proteinase<br />was uniformly increasing in all experimental groups during simulating of ALI induced by administration of<br />hydrochloric acid (p&lt;0.001). When comparing the results of caspase course of apoptosis it was defined that,<br />despite the progressive increase in caspase-3 rate in lung homogenate, cysteine proteinase rate in plasma did<br />not change.<br />The receptor mechanism of apoptosis was studied by establishing correlation relationships with the number<br />of cells carrying membrane binding TNF type 1 (TNF-R1) receptor. A strong positive correlation relationship<br />between the number of neutrophils with TNF-R1 and caspase-3 rate in lungs of all research groups was<br />determined.<br />Conclusions. The implementation of neutrophils death by apoptosis is caused by change of activity of<br />caspase cascade effector components, such as caspase-3, in cases of ALI induced by intratracheal administration<br />of hydrochloric acid. One of the potential mechanisms responsible for the activation of caspase course is excessive<br />generation of active forms of oxygen and increase in the number of neutrophils carrying membrane binding TNF<br />receptor type 1.<br />KEY WORDS: caspase-3, tumour necrosis factor alpha receptor 1, acute lung injury</p>

scholarly journals Haplotype Association Mapping of Acute Lung Injury in Mice Implicates Activin A Receptor, Type 1

2011 ◽  
Vol 183 (11) ◽  
pp. 1499-1509 ◽  
Author(s):  
George D. Leikauf ◽  
Vincent J. Concel ◽  
Pengyuan Liu ◽  
Kiflai Bein ◽  
Annerose Berndt ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Association Mapping ◽  
Activin A ◽  
Receptor Type ◽  
Haplotype Association

scholarly journals Rat model of smoke inhalation-induced acute lung injury

2021 ◽  
Vol 8 (1) ◽  
pp. e000879
Author(s):  
Premila Devi Leiphrakpam ◽  
Hannah R Weber ◽  
Tobi Ogun ◽  
Keely L Buesing
Keyword(s):  
Animal Model ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Caspase 3 ◽  
Small Animal ◽  
Therapeutic Options ◽  
Smoke Inhalation ◽  
Small Animal Model ◽  
Injury Score ◽  
Confounding Variables

BackgroundAcute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a lethal disease with limited therapeutic options and an unacceptably high mortality rate. Understanding the complex pathophysiological processes involved in the development of ALI/ARDS is critical for developing novel therapeutic strategies. Smoke inhalation (SI) injury is the leading cause of morbidity and mortality in patients with burn-associated ALI/ARDS; however, to our knowledge few reliable, reproducible models are available for pure SI animal model to investigate therapeutic options for ALI/ARDS without the confounding variables introduced by cutaneous burn or other pathology.ObjectiveTo develop a small animal model of pure SI-induced ALI and to use this model for eventual testing of novel therapeutics for ALI.MethodsRats were exposed to smoke using a custom-made smoke generator. Peripheral oxygen saturation (SpO2), heart rate, arterial blood gas, and chest X-ray (CXR) were measured before and after SI. Wet/dry weight (W/D) ratio, lung injury score and immunohistochemical staining of cleaved caspase 3 were performed on harvested lung tissues of healthy and SI animals.ResultsThe current study demonstrates the induction of ALI in rats after SI as reflected by a significant, sustained decrease in SpO2 and the development of diffuse bilateral pulmonary infiltrates on CXR. Lung tissue of animals exposed to SI showed increased inflammation, oedema and apoptosis as reflected by the increase in W/D ratio, injury score and cleaved caspase 3 level of the harvested tissues compared with healthy animals.ConclusionWe have successfully developed a small animal model of pure SI-induced ALI. This model is offered to the scientific community as a reliable model of isolated pulmonary SI-induced injury without the confounding variables of cutaneous injury or other systemic pathology to be used for study of novel therapeutics or other investigation.

scholarly journals Photobiomodulation prevents DNA fragmentation of alveolar epithelial cells and alters the mRNA levels of caspase 3 and Bcl-2 genes in acute lung injury

2018 ◽  
Vol 17 (7) ◽  
pp. 975-983 ◽  
Author(s):  
Luiz Philippe da Silva Sergio ◽  
Andrezza Maria Côrtes Thomé ◽  
Larissa Alexsandra da Silva Neto Trajano ◽  
Andre Luiz Mencalha ◽  
Adenilson de Souza da Fonseca ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Epithelial Cells ◽  
Lung Injury ◽  
Dna Fragmentation ◽  
Caspase 3 ◽  
Alveolar Epithelial Cells ◽  
Mrna Levels ◽  
Alveolar Epithelial ◽  
Life Threatening ◽  
Pulmonary Permeability

Acute lung injury (ALI) is defined as hyperinflammation that could occur from sepsis and lead to pulmonary permeability and edema, making them life-threatening diseases.

Silencing of Fas, FADD (Fas-Associated Via Death Domain) or Caspase-3 Differentially Affects Lung Inflammation, Apoptosis and Development of Trauma Induced Septic Acute Lung Injury (ALI)

Shock ◽  
2013 ◽  
pp. 1
Author(s):  
Mirko Philipp Messer ◽  
Philipp Kellermann ◽  
Sascha Jörn Weber ◽  
Christoph Hohmann ◽  
Stephanie Denk ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Lung Inflammation ◽  
Caspase 3 ◽  
Death Domain

scholarly journals Oxidative lipidomics of hyperoxic acute lung injury: mass spectrometric characterization of cardiolipin and phosphatidylserine peroxidation

2010 ◽  
Vol 299 (1) ◽  
pp. L73-L85 ◽  
Author(s):  
Yulia Y. Tyurina ◽  
Vladimir A. Tyurin ◽  
A. Murat Kaynar ◽  
Valentyna I. Kapralova ◽  
Karla Wasserloos ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Molecular Species ◽  
Caspase 3 ◽  
Ionization Mass ◽  
Individual Molecular Species ◽  
Pulmonary Endothelium ◽  
Anionic Phospholipids ◽  
Pulmonary Endothelial Cells

Reactive oxygen species have been shown to play a significant role in hyperoxia-induced acute lung injury, in part, by inducing apoptosis of pulmonary endothelium. However, the signaling roles of phospholipid oxidation products in pulmonary endothelial apoptosis have not been studied. Using an oxidative lipidomics approach, we identified individual molecular species of phospholipids involved in the apoptosis-associated peroxidation process in a hyperoxic lung. C57BL/6 mice were killed 72 h after exposure to hyperoxia (100% oxygen). We found that hyperoxia-induced apoptosis (documented by activation of caspase-3 and -7 and histochemical terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling staining of pulmonary endothelium) was accompanied by nonrandom oxidation of pulmonary lipids. Two anionic phospholipids, mitochondria-specific cardiolipin (CL) and extramitochondrial phosphatidylserine (PS), were the two major oxidized phospholipids in hyperoxic lung. Using electrospray ionization mass spectrometry, we identified several oxygenation products in CL and PS. Quantitative assessments revealed a significant decrease of CL and PS molecular species containing C18:2, C20:4, C22:5, and C22:6 fatty acids. Similarly, exposure of mouse pulmonary endothelial cells (MLEC) to hyperoxia (95% oxygen; 72 h) resulted in activation of caspase-3 and -7 and significantly decreased the content of CL molecular species containing C18:2 and C20:4 as well as PS molecular species containing C22:5 and C22:6. Oxygenated molecular species were found in the same two anionic phospholipids, CL and PS, in MLEC exposed to hyperoxia. Treatment of MLEC with a mitochondria-targeted radical scavenger, a conjugate of hemi-gramicidin S with nitroxide, XJB-5-131, resulted in significantly lower oxidation of both CL and PS and a decrease in hyperoxia-induced changes in caspase-3 and -7 activation. We speculate that cytochrome c driven oxidation of CL and PS is associated with the signaling role of these oxygenated species participating in the execution of apoptosis and clearance of pulmonary endothelial cells, thus contributing to hyperoxic lung injury.

scholarly journals Neutrophil Proteinases in Hydrochloric Acid- and Endotoxin-Induced Acute Lung Injury: Evaluation of Interstitial Protease Activity by in situ Zymography

2002 ◽  
Vol 82 (2) ◽  
pp. 133-145 ◽  
Author(s):  
Andry Van de Louw ◽  
Daniel Jean ◽  
Eric Frisdal ◽  
Charles Cerf ◽  
Marie-Pia d'Ortho ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Hydrochloric Acid ◽  
Lung Injury ◽  
Protease Activity ◽  
In Situ Zymography

Angiotensin II and the fibroproliferative response to acute lung injury

2004 ◽  
Vol 286 (1) ◽  
pp. L156-L164 ◽  
Author(s):  
Richard P. Marshall ◽  
Peter Gohlke ◽  
Rachel C. Chambers ◽  
David C. Howell ◽  
Steve E. Bottoms ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Angiotensin Ii ◽  
Lung Injury ◽  
Ace Inhibitors ◽  
Transforming Growth Factor ◽  
Lung Fibroblasts ◽  
Collagen Deposition ◽  
Ang Ii ◽  
Potent Inducer

Angiotensin II (ANG II), generated by activation of local renin-angiotensin systems, is believed to play an important role in tissue repair and remodeling, in part via transforming growth factor-β (TGF-β). Angiotensin-converting enzyme (ACE) inhibitors have been shown to abrogate experimental lung injury via a number of potential mechanisms; however, the potentially fibroproliferative role for ANG II in the lung has not been characterized. We hypothesized that, after lung injury, ANG II would stimulate fibroblast procollagen synthesis and promote lung collagen deposition in rats. In vitro, ANG II was a potent inducer of procollagen production in human lung fibroblasts via activation of the type 1 receptor and, at least in part, via the autocrine action of TGF-β. After bleomycin-induced lung injury, an increase in lung ANG II concentration was observed by day 3 that preceded increases in lung collagen and was maintained until death at day 21. Administration of an ACE inhibitor (ramipril) reduced ACE activity, ANG II concentration, TGF-β expression, and collagen deposition. Losartan (an ANG II type 1 receptor antagonist) also attenuated the increase in TGF-β expression and lung collagen deposition. These observations suggest that ANG II, possibly generated locally within the lung, may play an important role in the fibrotic response to acute lung injury, at least in part via the action of TGF-β. ACE inhibitors and receptor antagonists, already widely used clinically, should be assessed as potential new therapies for fibrotic lung disease.

scholarly journals СУБМІКРОСКОПІЧНІ ЗМІНИ КОМПОНЕНТІВ АЕРОГЕМАТИЧНОГО БАР’ЄРУ РЕСПІРАТОРНОГО ВІДДІЛУ ЛЕГЕНЬ ЩУРІВ У РАННІ ТЕРМІНИ ПІСЛЯ ГОСТРОГО УРАЖЕННЯ ХЛОРИДНОЮ КИСЛОТОЮ

2018 ◽  
Author(s):  
V. O. Beskyy ◽  
Z. M. Nebesna ◽  
M. I. Marushchak ◽  
L. A. Hryshchuk
Keyword(s):  
Acute Lung Injury ◽  
Hydrochloric Acid ◽  
Lung Injury ◽  
Early Period ◽  
Alveolar Epithelium ◽  
Male Rats ◽  
Control Group ◽  
Ultrastructural Organization ◽  
Type I ◽  
White Rats

Submicroscopic studies of the respiratory part of the lungs after 2 and 6 hours after the experimental acute lung injury with hydrochloric acid established adaptive-compensatory and destructive changes in the components of the air-blood barrier.The aim of the study – to learn submicroscopic changes in the components of the air-blood barrier of the lungs in the early period after acute lung injury.Materials and Methods. The experiments were carried out on 30 white mature non-linear male rats weighing 200–220 g. The animals were divided into 3 groups: 1 – control group, 2 – hydrochloric acid damage after 2 hours, 3 – hydrochloric acid damage after 6 hour.Results and Discussion. In an experiment on mature white rats, a study was made of the submicroscopic state of the components of the air-blood barrier in the early periods after acute lung injury. It has been established that adaptive-compensatory and initial destructive changes of the alveolar epithelium and the walls of the hemocapillary take place at 2 o'clock in the experiment. The cytoplasm of respiratory epitheliocytes during this period of the experiment was focal-edematous and enlightened, organelles were destructively altered. For alveolocytes of type I, there was a significant swelling and clarification of the cytoplasm. During this period of the experiment, an increased number of actively phagocytizing macrophages appeared, which acquired a rounded shape, clearly contoured membranes of the cariolema, their invaginations were determined, and in the karyoplasm euchromatin predominated. In alveolocytes of type II, after 6 hours, the progression of destructive changes was established. For which there were peculiarity hypertrophied nuclei with deep invagination of the cariolema, in which there were few nuclear pores, locally expanded perinuclear space. In the edematous cytoplasm, organelles were found to be destructively altered.Conclusions. Acute damage to the lungs leads to a disruption of the ultrastructural organization of the air-blood barrier. Established adaptive-compensatory processes and signs of destructive changes in the alveolar epithelium and the walls of hemocapillaries, which leads to deterioration of gas-exchange processes in the lungs.

Investigation of anti-inflammatory effects of oxygen nanobubbles in a rat hydrochloric acid lung injury model

Nanomedicine ◽  
2020 ◽  
Vol 15 (27) ◽  
pp. 2647-2654
Author(s):  
Keisuke Yoshida ◽  
Yukihiro Ikegami ◽  
Shinju Obara ◽  
Keiko Sato ◽  
Masahiro Murakawa
Keyword(s):  
Acute Lung Injury ◽  
Mean Arterial Pressure ◽  
Hydrochloric Acid ◽  
Lung Injury ◽  
Arterial Pressure ◽  
Rat Model ◽  
Injury Model ◽  
Lung Injury Model ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Aim: To investigate the anti-inflammatory effect of oxygen nanobubbles (ONBs) in an acute lung injury rat model. Materials & methods: In a rat hydrochloric acid lung injury model, ONB fluid was administered intravenously in the ONB group (n = 6) and normal saline was administered in the control group (n = 6). 4 h later, arterial partial pressure of oxygen (PaO2), mean arterial pressure and plasma inflammatory cytokines were measured. Results: There were no significant differences in the PaO2, mean arterial pressure or TNF-α and IL-6 levels between the two groups. Conclusions: No anti-inflammatory effect could be confirmed at the present ONB dose in the rat model of acute lung injury.

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