Effects of rapamycin and OSI-027 on α-SMA in lung tissue of SD rat pups with hyperoxic lung injury

2021 ◽  
Vol 556 ◽  
pp. 39-44
Author(s):  
Mulin Liang ◽  
Hongxing Dang ◽  
Qinghe Li ◽  
Weiben Huang ◽  
Chengjun Liu
Keyword(s):  
Lung Injury ◽  
Lung Tissue ◽  
Rat Pups ◽  
Sd Rat ◽  
Hyperoxic Lung Injury

Attenuation of hyperoxic lung injury by the 21-aminosteroid U-74389G

1995 ◽  
Vol 78 (5) ◽  
pp. 1635-1641 ◽  
Author(s):  
S. Tasaka ◽  
A. Ishizaka ◽  
T. Urano ◽  
K. Sayama ◽  
F. Sakamaki ◽  
...  
Keyword(s):  
Lung Injury ◽  
Lung Tissue ◽  
Guinea Pigs ◽  
Weight Ratio ◽  
Dry Weight ◽  
Endothelial Damage ◽  
Lung Water ◽  
Tissue Samples ◽  
Cell Accumulation ◽  
Hyperoxic Lung Injury

Hyperoxic lung injury is attributable to oxygen radicals produced under hyperoxic conditions. The 21-aminosteroid (AS), U-74389G, is a potent antioxidant. We examined the effect of U-74389G on lung injury in guinea pigs during exposure to 90% O2 for 48 h. We injected either vehicle or 10 mg/kg of U-74389G 30 min before the O2 exposure and injected the same dose 12, 24, and 36 h later. We performed two series of experiments after exposure. In the first series, we measured the clearance rate of 99mTc-labeled dialdehyde starch (DAS) from the lungs as an index of pulmonary epithelial damage in three experimental groups consisting of 1) control (n = 6) O2 alone (n = 6), and 3) O2 + AS (n = 6). In the second series, pulmonary endothelial injury was estimated by using 28 guinea pigs divided into four experimental groups consisting of 1) control (n = 8), 2) AS alone (n = 5), 3) O2 alone (n = 6), and 4) O2 + AS (n = 9). In the second series, we measured the wet-to-dry weight ratio (W/D) as an index of lung water and the concentration ratio of 125I-labeled albumin in lung tissue and bronchoalveolar lavage (BAL) fluid compared with plasma (T/P and BAL/P, respectively) as indexes of pulmonary endothelial damage. Cell accumulation in BAL fluid and lung tissue samples was also assessed in the second series.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals OPTICAL IMAGING OF LIPOPOLYSACCHARIDE-INDUCED OXIDATIVE STRESS IN ACUTE LUNG INJURY FROM HYPEROXIA AND SEPSIS

2013 ◽  
Vol 06 (03) ◽  
pp. 1350017 ◽  
Author(s):  
REYHANEH SEPEHR ◽  
SAID H. AUDI ◽  
SEPIDEH MALEKI ◽  
KEVIN STANISZEWSKI ◽  
ANNIE L. EIS ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Optical Imaging ◽  
Premature Infants ◽  
Lung Tissue ◽  
Oxygen Toxicity ◽  
Neonatal Rat ◽  
Redox States ◽  
Rat Pups

Reactive oxygen species (ROS) have been implicated in the pathogenesis of many acute and chronic pulmonary disorders such as acute lung injury (ALI) in adults and bronchopulmonary dysplasia (BPD) in premature infants. Bacterial infection and oxygen toxicity, which result in pulmonary vascular endothelial injury, contribute to impaired vascular growth and alveolar simplification seen in the lungs of premature infants with BPD. Hyperoxia induces ALI, reduces cell proliferation, causes DNA damage and promotes cell death by causing mitochondrial dysfunction. The objective of this study was to use an optical imaging technique to evaluate the variations in fluorescence intensities of the auto-fluorescent mitochondrial metabolic coenzymes, NADH and FAD in four different groups of rats. The ratio of these fluorescence signals (NADH/FAD), referred to as NADH redox ratio (NADH RR) has been used as an indicator of tissue metabolism in injuries. Here, we investigated whether the changes in metabolic state can be used as a marker of oxidative stress caused by hyperoxia and bacterial lipopolysaccharide (LPS) exposure in neonatal rat lungs. We examined the tissue redox states of lungs from four groups of rat pups: normoxic (21% O2 ) pups, hyperoxic (90% O2 ) pups, pups treated with LPS (normoxic + LPS), and pups treated with LPS and hyperoxia (hyperoxic + LPS). Our results show that hyperoxia oxidized the respiratory chain as reflected by a ~ 31% decrease in lung tissue NADH RR as compared to that for normoxic lungs. LPS treatment alone or with hyperoxia had no significant effect on lung tissue NADH RR as compared to that for normoxic or hyperoxic lungs, respectively. Thus, NADH RR serves as a quantitative marker of oxidative stress level in lung injury caused by two clinically important conditions: hyperoxia and LPS exposure.

scholarly journals Angiotensin-converting enzyme 2 attenuates inflammatory response and oxidative stress in hyperoxic lung injury by regulating NF-κB and Nrf2 pathways

QJM ◽  
2019 ◽  
Vol 112 (12) ◽  
pp. 914-924 ◽  
Author(s):  
Y Fang ◽  
F Gao ◽  
Z Liu
Keyword(s):  
Oxidative Stress ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Lung Tissue ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Hyperoxic Lung Injury ◽  
Expression Activity ◽  
And Oxidative Stress

Summary Objective To investigate the role of angiotensin-converting enzyme 2 (ACE2) in hyperoxic lung injury. Methods Adult mice were exposed to 95% O2 for 72 h to induce hyperoxic lung injury, and simultaneously treated with ACE2 agonist diminazene aceturate (DIZE) or inhibitor MLN-4760. ACE2 expression/activity in lung tissue and angiotensin (Ang)-(1–7)/Ang II in bronchoalveolar lavage fluid (BALF), and the severity of hyperoxic lung injury were evaluated. The levels of inflammatory factors in BALF and lung tissue and the expression levels of phospho-p65, p65 and IkBα were measured. Oxidative parameter and antioxidant enzyme levels in lung tissue were measured to assess oxidative stress. Finally, the expression levels of nuclear factor-erythroid-2-related factor (Nrf2), NAD(P)H quinine oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1) were measured using Western blotting. Results Hyperoxia treatment significantly decreased lung ACE2 expression/activity and increased the Ang II/Ang-(1–7) ratio, while co-treatment with hyperoxia and DIZE significantly increased lung ACE2 expression/activity and decreased the Ang II/Ang-(1–7) ratio. By contrast, co-treatment with hyperoxia and MLN-4760 significantly decreased lung ACE2 expression/activity and increased the Ang II/Ang-(1–7) ratio. Hyperoxia treatment induced significant lung injury, inflammatory response and oxidative stress, which were attenuated by DIZE but aggravated by MLN-4760. The NF-κB pathways were activated by hyperoxia and MLN-4760 but inhibited by DIZE. The Nrf2 pathway and its downstream proteins NQO1 and HO-1 were activated by DIZE but inhibited by MLN-4760. Conclusion Activation of ACE2 can reduce the severity of hyperoxic lung injury by inhibiting inflammatory response and oxidative stress. ACE2 can inhibit the NF-κB pathway and activate the Nrf2/HO-1/NQO1 pathway, which may be involved in the underlying mechanism.

Glutathione supplements protect preterm rabbits from oxidative lung injury

1996 ◽  
Vol 270 (3) ◽  
pp. L446-L451 ◽  
Author(s):  
L. A. Brown ◽  
J. A. Perez ◽  
F. L. Harris ◽  
R. H. Clark
Keyword(s):  
Lung Injury ◽  
Cell Viability ◽  
Lung Tissue ◽  
Nutritional Support ◽  
Lung Compliance ◽  
Lung Mechanics ◽  
Peritoneal Catheter ◽  
Lung Volumes ◽  
Hyperoxic Lung Injury

The main objective of this study was to determine if glutathione (GSH) supplementation attenuated hyperoxic lung injury. Preterm (29 days) rabbits were delivered and exposed for 24 h to 1) room air, 2) room air and GSH, 3) 95% oxygen and GSH. GSH supplements (1 mM) were delivered in the nutritional support of 10% dextrose and saline through a peritoneal catheter. Animals assigned to oxygen had decreased lung volumes at 35 cmH2O, decreased lung compliance, increased edema, decreased cell viability, and decreased lung tissue and lavage-reduced/oxidized GSH levels, compared with control animals. Despite exposure to hyperoxia, animals supplemented with GSH were not different from room air controls with respect to lung mechanics, edema, cell viability, or tissue and lavage GSH. These studies suggest that GSH supplementation maintains normal lavage and lung tissue GSH levels in preterm animals exposed to hyperoxia and attenuates the changes in lung mechanics associated with oxygen-induced lung injury.

scholarly journals Pentoxifylline reduces fibrin deposition and prolongs survival in neonatal hyperoxic lung injury

2004 ◽  
Vol 97 (5) ◽  
pp. 2014-2019 ◽  
Author(s):  
Simone A. J. ter Horst ◽  
Gerry T. M. Wagenaar ◽  
Eveline de Boer ◽  
Margôt A. van Gastelen ◽  
Joost C. M. Meijers ◽  
...  
Keyword(s):  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Total Protein ◽  
Protein Concentration ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Fibrin Deposition ◽  
Total Protein Concentration ◽  
Rat Pups ◽  
Hyperoxic Lung Injury

Bronchopulmonary dysplasia is a leading cause of mortality and morbidity in preterm infants despite improved treatment modalities. Pentoxifylline, a phosphodiesterase inhibitor, inhibits multiple processes that lead to neonatal hyperoxic lung injury, including inflammation, coagulation, and edema. Using a preterm rat model, we investigated the effects of pentoxifylline on hyperoxia-induced lung injury and survival. Preterm rat pups were exposed to 100% oxygen and injected subcutaneously with 0.9% saline or 75 mg/kg pentoxifylline twice a day. On day 10, lung tissue was harvested for histology, fibrin deposition, and mRNA expression, and bronchoalveolar lavage fluid was collected for total protein concentration. Pentoxifylline treatment increased mean survival by 3 days ( P = 0.0018) and reduced fibrin deposition by 66% ( P < 0.001) in lung homogenates compared with untreated hyperoxia-exposed controls. Monocyte chemoattractant protein-1 expression in lung homogenates was decreased, but the expressions of TNF-α, IL-6, matrix metalloproteinase-12, tissue factor, and plasminogen activator inhibitor-1 were similar in both groups. Total protein concentration in bronchoalveolar lavage fluid was decreased by 33% ( P = 0.029) in the pentoxifylline group. Pentoxifylline treatment attenuates alveolar fibrin deposition and prolongs survival in preterm rat pups with neonatal hyperoxic lung injury, probably by reducing capillary-alveolar protein leakage.

Therapeutic effects of fibroblast grow factor 10 (FGF 10) after hyperoxic lung injury in mice

Pneumologie ◽  
2014 ◽  
Vol 68 (06) ◽  
Author(s):  
CM Chao ◽  
D Al Alam ◽  
R Schermuly ◽  
H Ehrhardt ◽  
KP Zimmer ◽  
...  
Keyword(s):  
Lung Injury ◽  
Therapeutic Effects ◽  
Hyperoxic Lung Injury

Synergistic Effects of Aurothioglucose and Hyperoxia in Neonatal Hyperoxic Lung Injury

2016 ◽  
Vol 100 ◽  
pp. S113-S114
Author(s):  
Stephanie Wall ◽  
Rachael Tindell ◽  
Katelyn Dunigan ◽  
Rui Li ◽  
Qian Li ◽  
...  
Keyword(s):  
Lung Injury ◽  
Synergistic Effects ◽  
Hyperoxic Lung Injury

scholarly journals The relationship between complement C3 expression and the MUC5B genotype in pulmonary fibrosis

2018 ◽  
Vol 315 (1) ◽  
pp. L1-L10 ◽  
Author(s):  
Tsukasa Okamoto ◽  
Susan K. Mathai ◽  
Corinne E. Hennessy ◽  
Laura A. Hancock ◽  
Avram D. Walts ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Lung Injury ◽  
Lung Tissue ◽  
Complement System ◽  
Fold Increase ◽  
Complement C3 ◽  
Healthy Controls ◽  
C3 Gene ◽  
The Relationship ◽  
The Complement System

The common gain-of-function MUC5B promoter variant ( rs35705950 ) is the strongest risk factor for the development of idiopathic pulmonary fibrosis (IPF). While the role of complement in IPF is controversial, both MUC5B and the complement system play a role in lung host defense. The aim of this study was to evaluate the relationship between complement component 3 (C3) and MUC5B in patients with IPF and in bleomycin-induced lung injury in mice. To do this, we evaluated C3 gene expression in whole lung tissue from 300 subjects with IPF and 175 healthy controls. Expression of C3 was higher in IPF than healthy controls {1.40-fold increase [95% confidence interval (CI) 1.31–1.50]; P < 0.0001} and even greater among IPF subjects with the highest-risk IPF MUC5B promoter genotype [TT vs. GG = 1.59-fold (95% CI 1.15–2.20); P < 0.05; TT vs. GT = 1.66-fold (95% CI 1.20–2.30); P < 0.05]. Among subjects with IPF, C3 expression was significantly higher in the lung tissue without microscopic honeycombing than in the lung tissue with microscopic honeycombing [1.40-fold increase (95% CI 1.23– 1.59); P < 0.01]. In mice, while bleomycin exposure increased Muc5b protein expression, C3-deficient mice were protected from bleomycin-induced lung injury. In aggregate, our findings indicate that the MUC5B promoter variant is associated with higher C3 expression and suggest that the complement system may contribute to the pathogenesis of IPF.

Pulmonary Ferritin: Differential Effects of Hyperoxic Lung Injury on Subunit mRNA Levels

1997 ◽  
Vol 22 (5) ◽  
pp. 901-908 ◽  
Author(s):  
Timothy P Ryan ◽  
Raymond F Krzesicki ◽  
David P Blakeman ◽  
Jia En Chin ◽  
Robert L Griffin ◽  
...  
Keyword(s):  
Lung Injury ◽  
Mrna Levels ◽  
Differential Effects ◽  
Subunit Mrna ◽  
Hyperoxic Lung Injury
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