scholarly journals Inhaled carbon monoxide and hyperoxic lung injury in rats

2001 ◽  
Vol 281 (4) ◽  
pp. L949-L957 ◽  
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.

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 Ganoderic acid A attenuates lipopolysaccharide-induced lung injury in mice

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Bing Wan ◽  
Yan Li ◽  
Shuangshuang Sun ◽  
Yang Yang ◽  
Yanling LV ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Mouse Model ◽  
Weight Ratio ◽  
Dry Weight ◽  
Lavage Fluid ◽  
Myeloperoxidase Activity ◽  
Protective Effects ◽  
Ganoderic Acid ◽  
Lower Lung

Abstract The present study aimed to investigate the protective effects of ganoderic acid A (GAA) on lipopolysaccharide (LPS)-induced acute lung injury. In mouse model of LPS-induced acute lung injury, we found that GAA led to significantly lower lung wet-to-dry weight ratio and lung myeloperoxidase activity, and attenuated pathological damages. In addition, GAA increased superoxide dismutase activity, but decreased malondialdehyde content and proinflammatory cytokines levels in the bronchoalveolar lavage fluid. Mechanistically, GAA reduced the activation of Rho/ROCK/NF-κB pathway to inhibit LPS-induced inflammation. In conclusion, our study suggests that GAA attenuates acute lung injury in mouse model via the inhibition of Rho/ROCK/NF-κB pathway.

scholarly journals Therapeutic Applications of Carbon Monoxide

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Melissa Knauert ◽  
Sandeep Vangala ◽  
Maria Haslip ◽  
Patty J. Lee
Keyword(s):  
Carbon Monoxide ◽  
Lung Injury ◽  
Ischemia Reperfusion ◽  
Heme Oxygenase 1 ◽  
Protective Effects ◽  
Phase Ii Trials ◽  
Therapeutic Implications ◽  
Damage Models ◽  
Therapeutic Benefits ◽  
Stress States

Heme oxygenase-1 (HO-1) is a regulated enzyme induced in multiple stress states. Carbon monoxide (CO) is a product of HO catalysis of heme. In many circumstances, CO appears to functionally replace HO-1, and CO is known to have endogenous anti-inflammatory, anti-apoptotic, and antiproliferative effects. CO is well studied in anoxia-reoxygenation and ischemia-reperfusion models and has advanced to phase II trials for treatment of several clinical entities. In alternative injury models, laboratories have used sepsis, acute lung injury, and systemic inflammatory challenges to assess the ability of CO to rescue cells, organs, and organisms. Hopefully, the research supporting the protective effects of CO in animal models will translate into therapeutic benefits for patients. Preclinical studies of CO are now moving towards more complex damage models that reflect polymicrobial sepsis or two-step injuries, such as sepsis complicated by acute respiratory distress syndrome. Furthermore, co-treatment and post-treatment with CO are being explored in which the insult occurs before there is an opportunity to intervene therapeutically. The aim of this review is to discuss the potential therapeutic implications of CO with a focus on lung injury and sepsis-related models.

scholarly journals Mitigation of chlorine gas lung injury in rats by postexposure administration of sodium nitrite

2011 ◽  
Vol 300 (3) ◽  
pp. L362-L369 ◽  
Author(s):  
Amit K. Yadav ◽  
Stephen F. Doran ◽  
Andrey A. Samal ◽  
Ruchita Sharma ◽  
Kokilavani Vedagiri ◽  
...  
Keyword(s):  
Lung Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Weight Ratio ◽  
Dry Weight ◽  
Airway Epithelial Cells ◽  
Normal Lung ◽  
Protective Effects ◽  
Quantitative Morphology ◽  
Upper Airways

Nitrite (NO2−) has been shown to limit injury to the heart, liver, and kidneys in various models of ischemia-reperfusion injury. Potential protective effects of systemic NO2− in limiting lung injury or enhancing repair have not been documented. We assessed the efficacy and mechanisms by which postexposure intraperitoneal injections of NO2− mitigate chlorine (Cl2)-induced lung injury in rats. Rats were exposed to Cl2 (400 ppm) for 30 min and returned to room air. NO2− (1 mg/kg) or saline was administered intraperitoneally at 10 min and 2, 4, and 6 h after exposure. Rats were killed at 6 or 24 h. Injury to airway and alveolar epithelia was assessed by quantitative morphology, protein concentrations, number of cells in bronchoalveolar lavage (BAL), and wet-to-dry lung weight ratio. Lipid peroxidation was assessed by measurement of lung F2-isoprostanes. Rats developed severe, but transient, hypoxemia. A significant increase of protein concentration, neutrophil numbers, airway epithelia in the BAL, and lung wet-to-dry weight ratio was evident at 6 h after Cl2 exposure. Quantitative morphology revealed extensive lung injury in the upper airways. Airway epithelial cells stained positive for terminal deoxynucleotidyl-mediated dUTP nick end labeling (TUNEL), but not caspase-3. Administration of NO2− resulted in lower BAL protein levels, significant reduction in the intensity of the TUNEL-positive cells, and normal lung wet-to-dry weight ratios. F2-isoprostane levels increased at 6 and 24 h after Cl2 exposure in NO2−- and saline-injected rats. This is the first demonstration that systemic NO2− administration mitigates airway and epithelial injury.

scholarly journals Lung-specific induction of heme oxygenase-1 and hyperoxic lung injury

1998 ◽  
Vol 274 (4) ◽  
pp. L582-L590 ◽  
Author(s):  
Jennifer L. Taylor ◽  
Martha Sue Carraway ◽  
Claude A. Piantadosi
Keyword(s):  
Oxidative Stress ◽  
Enzyme Activity ◽  
Lung Injury ◽  
Heme Oxygenase ◽  
Normal Saline ◽  
Dry Weight ◽  
Heme Oxygenase 1 ◽  
Specific Induction ◽  
Hyperoxic Lung Injury ◽  
Tin Protoporphyrin

Heme oxygenase (HO)-1, which catalyzes heme breakdown, is induced by oxidative stress and may protect against oxidative injury. We hypothesized that induction of HO-1 by hemoglobin (Hb) in the lung would protect the rat from pulmonary O2 toxicity. Rats given intratracheal (IT) Hb showed lung-specific induction of HO-1 by 8 h by Western analysis. Rats were then pretreated for 8 h before 60 h of exposure to 100% O2 with either IT normal saline, Hb, or Hb plus the HO-1 inhibitor tin-protoporphyrin (SnPP). Both the Hb+O2 and Hb+O2+ SnPP animals had less lung injury than normal saline controls as indicated by lower pleural fluid volumes and wet-to-dry weight ratios ( P < 0.01). The improvement in injury in the two Hb-treated groups was the same despite a 61% decrease in HO enzyme activity in the Hb+SnPP group after 60 h of O2. In addition, inhibition of HO activity with SnPP alone before O2exposure did not augment the extent of hyperoxic lung injury. These results demonstrate that IT Hb induces lung HO-1 in the rat and protects against hyperoxia; however, the protection is not mediated by increased HO enzyme activity.

Adrenomedullin ameliorates lipopolysaccharide-induced acute lung injury in rats

2007 ◽  
Vol 293 (2) ◽  
pp. L446-L452 ◽  
Author(s):  
Takefumi Itoh ◽  
Hiroaki Obata ◽  
Shinsuke Murakami ◽  
Kaoru Hamada ◽  
Kenji Kangawa ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Total Protein ◽  
Intratracheal Instillation ◽  
Weight Ratio ◽  
Dry Weight ◽  
Alveolar Wall ◽  
Protective Effects ◽  
Tnf Α

Adrenomedullin (AM), an endogenous peptide, has been shown to have a variety of protective effects on the cardiovascular system. However, the effect of AM on acute lung injury remains unknown. Accordingly, we investigated whether AM infusion ameliorates lipopolysaccharide (LPS)-induced acute lung injury in rats. Rats were randomized to receive continuous intravenous infusion of AM (0.1 μg·kg−1·min−1) or vehicle through a microosmotic pump. The animals were intratracheally injected with either LPS (1 mg/kg) or saline. At 6 and 18 h after intratracheal instillation, we performed histological examination and bronchoalveolar lavage and assessed the lung wet/dry weight ratio as an index of acute lung injury. Then we measured the numbers of total cells and neutrophils and the levels of tumor necrosis factor (TNF)-α and cytokine-induced neutrophil chemoattractant (CINC) in bronchoalveolar lavage fluid (BALF). In addition, we evaluated BALF total protein and albumin levels as indexes of lung permeability. LPS instillation caused severe acute lung injury, as indicated by the histological findings and the lung wet/dry weight ratio. However, AM infusion attenuated these LPS-induced abnormalities. AM decreased the numbers of total cells and neutrophils and the levels of TNF-α and CINC in BALF. AM also reduced BALF total protein and albumin levels. In addition, AM significantly suppressed apoptosis of alveolar wall cells as indicated by cleaved caspase-3 staining. In conclusion, continuous infusion of AM ameliorated LPS-induced acute lung injury in rats. This beneficial effect of AM on acute lung injury may be mediated by inhibition of inflammation, hyperpermeability, and alveolar wall cell apoptosis.

Carbon monoxide provides protection against hyperoxic lung injury

1999 ◽  
Vol 276 (4) ◽  
pp. L688-L694 ◽  
Author(s):  
Leo E. Otterbein ◽  
Lin L. Mantell ◽  
Augustine M. K. Choi
Keyword(s):  
Oxidative Stress ◽  
Carbon Monoxide ◽  
Lung Injury ◽  
Neutrophil Infiltration ◽  
Protein Accumulation ◽  
Protective Effects ◽  
Low Concentration ◽  
Hyperoxic Lung Injury ◽  
Significant Attenuation

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.

scholarly journals Marathoners’ breathing pattern protects against lung injury by mechanical ventilation: a pilot study

2020 ◽  
Author(s):  
Yoshiaki Oshima ◽  
Naoto Okazaki ◽  
Akihiro Otsuki ◽  
Shunsaku Takahashi ◽  
Tomomi Harada ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Lung Injury ◽  
Time Allocation ◽  
Breathing Pattern ◽  
Weight Ratio ◽  
Dry Weight ◽  
Clinical Settings ◽  
Protective Effects ◽  
Ventilator Induced Lung Injury ◽  
Novel Method

Abstract Background: Marathoners use the 2:2 breathing pattern. We hypothesized that this ventilation method may protect against ventilator-induced lung injury.Methods: We studied the 2:2 breathing pattern as a mechanical ventilation mode, by assessing the gas exchange in intact rabbits and the pulmonary protective effects in isolated rabbit lungs. The typical setting of this breathing method was 30 cycles/min of respiratory frequency. The time allocation for one cycle was as follows: 1st inspiratory period, 2nd inspiratory period, 1st expiratory period, and 2nd expiratory period (all 0.3 s long) with intermittent resting periods (all 0.2 s).Results: The 2:2 breathing pattern caused no problems regarding the efficiency of oxygen uptake and carbon dioxide elimination. The wet-to-dry weight ratio of the lung was lower for the proposed 2:2 breathing pattern than with the inversed ratio ventilation (both inspiratory:expiratory ratio 1:1).Conclusions: The marathoners’ breathing pattern may be a novel method to provide protection against ventilator-induced lung injury in clinical settings.

scholarly journals Ginsenoside Rb1 Treatment Attenuates Pulmonary Inflammatory Cytokine Release and Tissue Injury following Intestinal Ischemia Reperfusion Injury in Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Ying Jiang ◽  
Zhen Zhou ◽  
Qing-tao Meng ◽  
Qian Sun ◽  
Wating Su ◽  
...  
Keyword(s):  
Lung Injury ◽  
Signaling Pathway ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Weight Ratio ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Ginsenoside Rb1 ◽  
Intestinal Ischemia Reperfusion

Objective. Intestinal ischemia reperfusion (II/R) injury plays a critical role in remote organ dysfunction, such as lung injury, which is associated with nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway. In the present study, we tested whether ginsenoside Rb1 attenuated II/R induced lung injury by Nrf2/HO-1 pathway.Methods. II/R injury was induced in male C57BL/6J mice by 45 min of superior mesenteric artery (SMA) occlusion followed by 2 hours of reperfusion. Ginsenoside Rb1 was administrated prior to reperfusion with or without ATRA (all-transretinoic acid, the inhibitor of Nrf2/ARE signaling pathway) administration before II/R.Results. II/R induced lung histological injury, which is accompanied with increased levels of malondialdehyde (MDA), interleukin- (IL-) 6, and tumor necrosis factor- (TNF-)αbut decreased levels of superoxide dismutase (SOD) and IL-10 in the lung tissues. Ginsenoside Rb1 reduced lung histological injury and the levels of TNF-αand MDA, as well as wet/dry weight ratio. Interestingly, the increased Nrf2 and HO-1 expression induced by II/R in the lung tissues was promoted by ginsenoside Rb1 treatment. All these changes could be inhibited or prevented by ATRA.Conclusion. Ginsenoside Rb1 is capable of ameliorating II/R induced lung injuries by activating Nrf2/HO-1 pathway.

Infused salbutamol accentuates acid-induced lung injury in the rat

1986 ◽  
Vol 71 (2) ◽  
pp. 205-209 ◽  
Author(s):  
Stanley Braude ◽  
David Royston
Keyword(s):  
Lung Injury ◽  
Intravenous Infusion ◽  
Time Course ◽  
Weight Ratio ◽  
Dry Weight ◽  
Adrenergic Agonist ◽  
Lung Water ◽  
Significant Difference ◽  
And Control ◽  
Control Infusion

1. The effect in the rat of salbutamol infusion (1 μg min−1 kg−1) on acid-induced lung injury has been determined. Severity of lung injury was assessed by two techniques: the pulmonary clearance of 99mTc-diethylenetriaminepenta-acetate (99mTc-DTPA) and the lung wet/dry weight ratio, giving indices of alveolar epithelial permeability and transendothelial water filtration respectively. 2. Mean half-time of clearance of 99mTc-DTPA was increased significantly in rats who had intratracheal acid-induced injury and control (saline) intravenous infusion (19.4 ± 2.6 min) compared with non-acid-treated rats (98.1 ± 7.2) (P < 0.0001). However, those animals who had intratracheal acid injury and subsequent salbutamol intravenous infusion had significantly faster clearance (11.5 ± 1.9) than the acid and control infusion group (P < 0.05). 3. Gravimetric lung water in the acid-only rats (expressed as wet/dry weight ratio) was increased significantly (6.4 ± 0.3) compared with the non-acid-treated controls (5.4 ± 0.2) (P < 0.01). Acid-treated rats who had salbutamol infused had dramatically increased lung water (10.0 ± 0.6) (P < 0.001 vs acid and control infusion). 4. Intravenous salbutamol infusion itself produced no significant difference in the results for both techniques, compared with the non-acid-treated time-course controls. 5. Infused salbutamol accentuates acid-induced lung injury in the rat. Possible factors responsible for these findings include β2-adrenergic agonist mediated inhibition of hypoxic pulmonary vasoconstriction (HPV) and a predominant β1-adrenergic agonist inotropic effect of salbutamol with resultant rise in pulmonary artery pressure.

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