Protective Effects Of Hydrogen Sulphide In Hyperoxic Lung Injury

Findings in recent years strongly suggest that the stress-inducible gene heme oxygenase (HO)-1 plays an important role in protection against oxidative stress. Although the mechanism(s) by which this protection occurs is poorly understood, we hypothesized that the gaseous molecule carbon monoxide (CO), a major by-product of heme catalysis by HO-1, may provide protection against oxidative stress. We demonstrate here that animals exposed to a low concentration of CO exhibit a marked tolerance to lethal concentrations of hyperoxia in vivo. This increased survival was associated with highly significant attenuation of hyperoxia-induced lung injury as assessed by the volume of pleural effusion, protein accumulation in the airways, and histological analysis. The lungs were completely devoid of lung airway and parenchymal inflammation, fibrin deposition, and pulmonary edema in rats exposed to hyperoxia in the presence of a low concentration of CO. Furthermore, exogenous CO completely protected against hyperoxia-induced lung injury in rats in which endogenous HO enzyme activity was inhibited with tin protoporphyrin, a selective inhibitor of HO. Rats exposed to CO also exhibited a marked attenuation of hyperoxia-induced neutrophil infiltration into the airways and total lung apoptotic index. Taken together, our data demonstrate, for the first time, that CO can be therapeutic against oxidative stress such as hyperoxia and highlight possible mechanism(s) by which CO may mediate these protective effects.

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The Protective Effects of Apocynin in Hyperoxic Lung Injury in Neonatal Rats

Pediatric Pulmonology ◽

10.1002/ppul.25707 ◽

2021 ◽

Author(s):

Ramazan Ozdemir ◽

Ismail Kursat Gokce ◽

Suat Tekin ◽

Aslı Cetin Taslıdere ◽

Hatice Turgut ◽

...

Keyword(s):

Lung Injury ◽

Protective Effects ◽

Neonatal Rats ◽

Hyperoxic Lung Injury

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Inhaled carbon monoxide and hyperoxic lung injury in rats

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.2001.281.4.l949 ◽

2001 ◽

Vol 281 (4) ◽

pp. L949-L957 ◽

Cited By ~ 35

Author(s):

Carolyn E. Clayton ◽

Martha Sue Carraway ◽

Hagir B. Suliman ◽

Edward D. Thalmann ◽

Katherine N. Thalmann ◽

...

Keyword(s):

Carbon Monoxide ◽

Lung Injury ◽

Pleural Fluid ◽

Manganese Superoxide Dismutase ◽

Apoptotic Cell ◽

Weight Ratio ◽

Dry Weight ◽

Heme Oxygenase 1 ◽

Protective Effects ◽

Hyperoxic Lung Injury

Because carbon monoxide (CO) has been proposed to have anti-inflammatory properties, we sought protective effects of CO in pulmonary O2 toxicity, which leads rapidly to lung inflammation and respiratory failure. Based on published studies, we hypothesized that CO protects the lung against O2 by selectively increasing expression of antioxidant enzymes, thereby decreasing oxidative injury and inflammation. Rats exposed to O2 with or without CO [50–500 parts/million (ppm)] for 60 h were compared for lung wet-to-dry weight ratio (W/D), pleural fluid volume, myeloperoxidase (MPO) activity, histology, expression of heme oxygenase-1 (HO-1), and manganese superoxide dismutase (Mn SOD) proteins. The brains were evaluated for histological evidence of damage from CO. In O2-exposed animals, lung W/D increased from 4.8 in normal rats to 6.3; however, only CO at 200 and 500 ppm decreased W/D significantly (to 5.9) during O2 exposure. Large volumes of pleural fluid accumulated in all rats, with no significant CO treatment effect. Lung MPO values increased after O2 and were not attenuated by CO treatment. CO did not enhance lung expression of oxidant-responsive proteins Mn SOD and HO-1. Animals receiving O2 and CO at 200 or 500 ppm showed significant apoptotic cell death in the cortex and hippocampus by immunochemical staining. Thus significant protection by CO against O2-induced lung injury could not be confirmed in rats, even at CO concentrations associated with apoptosis in the brain.

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Protective Effects of Valproic Acid, a Histone Deacetylase Inhibitor, against Hyperoxic Lung Injury in a Neonatal Rat Model

PLoS ONE ◽

10.1371/journal.pone.0126028 ◽

2015 ◽

Vol 10 (5) ◽

pp. e0126028 ◽

Cited By ~ 10

Author(s):

Merih Cetinkaya ◽

Mehmet Cansev ◽

Ferhat Cekmez ◽

Cuneyt Tayman ◽

Fuat Emre Canpolat ◽

...

Keyword(s):

Valproic Acid ◽

Lung Injury ◽

Histone Deacetylase ◽

Rat Model ◽

Histone Deacetylase Inhibitor ◽

Neonatal Rat ◽

Protective Effects ◽

Deacetylase Inhibitor ◽

Hyperoxic Lung Injury ◽

Neonatal Rat Model

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

Pneumologie ◽

10.1055/s-0034-1376795 ◽

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

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Synergistic Effects of Aurothioglucose and Hyperoxia in Neonatal Hyperoxic Lung Injury

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2016.10.293 ◽

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

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

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2021.02.061 ◽

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

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Protectin conjugates in tissue regeneration 1 restores lipopolysaccharide-induced pulmonary endothelial glycocalyx loss via ALX/SIRT1/NF-kappa B axis

Respiratory Research ◽

10.1186/s12931-021-01793-x ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Xin-Yang Wang ◽

Xin-Yu Li ◽

Cheng-Hua Wu ◽

Yu Hao ◽

Pan-Han Fu ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Inflammatory Cytokines ◽

Tissue Regeneration ◽

Umbilical Vein ◽

Endothelial Glycocalyx ◽

Lipid Mediator ◽

Protective Effects ◽

Pulmonary Vascular Permeability

Abstract Background Endothelial glycocalyx loss is integral to increased pulmonary vascular permeability in sepsis-related acute lung injury. Protectin conjugates in tissue regeneration 1 (PCTR1) is a novel macrophage-derived lipid mediator exhibiting potential anti-inflammatory and pro-resolving benefits. Methods PCTR1 was administrated intraperitoneally with 100 ng/mouse after lipopolysaccharide (LPS) challenged. Survival rate and lung function were used to evaluate the protective effects of PCTR1. Lung inflammation response was observed by morphology and inflammatory cytokines level. Endothelial glycocalyx and its related key enzymes were measured by immunofluorescence, ELISA, and Western blot. Afterward, related-pathways inhibitors were used to identify the mechanism of endothelial glycocalyx response to PCTR1 in mice and human umbilical vein endothelial cells (HUVECs) after LPS administration. Results In vivo, we show that PCTR1 protects mice against lipopolysaccharide (LPS)-induced sepsis, as shown by enhanced the survival and pulmonary function, decreased the inflammatory response in lungs and peripheral levels of inflammatory cytokines such as tumor necrosis factor-α, interleukin-6, and interleukin-1β. Moreover, PCTR1 restored lung vascular glycocalyx and reduced serum heparin sulphate (HS), syndecan-1 (SDC-1), and hyaluronic acid (HA) levels. Furthermore, we found that PCTR1 downregulated heparanase (HPA) expression to inhibit glycocalyx degradation and upregulated exostosin-1 (EXT-1) protein expression to promote glycocalyx reconstitution. Besides, we observed that BAY11-7082 blocked glycocalyx loss induced by LPS in vivo and in vitro, and BOC-2 (ALX antagonist) or EX527 (SIRT1 inhibitor) abolished the restoration of HS in response to PCTR1. Conclusion PCTR1 protects endothelial glycocalyx via ALX receptor by regulating SIRT1/NF-κB pathway, suggesting PCTR1 may be a significant therapeutic target for sepsis-related acute lung injury.

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