scholarly journals Amentoflavone prevents sepsis-associated acute lung injury through Nrf2-GCLc-mediated upregulation of glutathione

2016 ◽  
Vol 64 (1) ◽  
Author(s):  
Yuan Zong ◽  
Huali Zhang
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Lung Tissue ◽  
Medical Problem ◽  
Binding Activity ◽  
Content Increase ◽  
Protective Effects ◽  
Sod Activity ◽  
Buthionine Sulphoximine

Sepsis is a serious medical problem that is one of the main causes of high mortality in intensive care units. Fifty percent of patients with severe sepsis will develop acute lung injury (ALI). Amentoflavone (AMF) is a polyphenolic compound possessing potent anti-inflammatory activities. The present study was designed to explore the protective effects of AMF against ALI in CLP-induced septic rats. The results showed that AMF administration protected against septic ALI, as reflected by marked amelioration of histological injury of lung tissues and decrease of pulmonary edema in CLP-treated rats. AMF ameliorated CLP-induced increase of systemic and lung TNF-α and IL-1β and the binding activity of p65 NF-κB, indicating the inhibition of inflammation induced by CLP. Moreover, AMF prevented CLP-induced oxidative stress, as evidenced by increase of oxygen consumption rate, decrease of TBARS content, increase of SOD activity and GSH level in lung tissue of CLP-treated rats. CLP resulted in significant decrease of mRNA expression of Nrf2 and GCLc, which was inhibited by AMF. AMF-induced protective effects on ALI, inflammation, and oxidative stress were inhibited by lentivirus-mediated shRNA of Nrf2 and buthionine sulphoximine (BSO), an inhibitor of GSH synthesis. AMF increased Nrf2-binding activity with GCLc promoters in lung tissue of CLP-treated rats. The results suggested that AMF protected against ALI in septic rats through upregulation of Nrf2-GCLc signaling, enhancement of GSH antioxidant defense, reduction of oxidative stress and final amelioration of inflammation and histological injury of lung. The data provide new therapeutic options for the treatment of sepsis-associated ALI.

Biomarkers for oxidative stress in acute lung injury induced in rabbits submitted to different strategies of mechanical ventilation

2012 ◽  
Vol 112 (7) ◽  
pp. 1184-1190 ◽  
Author(s):  
Carlos Fernando Ronchi ◽  
Jose Roberto Fioretto ◽  
Ana Lucia Anjos Ferreira ◽  
Carolina Bragiola Berchieri-Ronchi ◽  
Camila Renata Correa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mechanical Ventilation ◽  
Dna Damage ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Comet Assay ◽  
Lung Tissue ◽  
Significant Positive Correlation ◽  
Target Tissue ◽  
Total Antioxidant

Oxidative damage has been said to play an important role in pulmonary injury, which is associated with the development and progression of acute respiratory distress syndrome (ARDS). We aimed to identify biomarkers to determine the oxidative stress in an animal model of acute lung injury (ALI) using two different strategies of mechanical ventilation. Rabbits were ventilated using either conventional mechanical ventilation (CMV) or high-frequency oscillatory ventilation (HFOV). Lung injury was induced by tracheal saline infusion (30 ml/kg, 38°C). In addition, five healthy rabbits were studied for oxidative stress. Isolated lymphocytes from peripheral blood and lung tissue samples were analyzed by alkaline single cell gel electrophoresis (comet assay) to determine DNA damage. Total antioxidant performance (TAP) assay was applied to measure overall antioxidant performance in plasma and lung tissue. HFOV rabbits had similar results to healthy animals, showing significantly higher antioxidant performance and lower DNA damage compared with CMV in lung tissue and plasma. Total antioxidant performance showed a significant positive correlation ( r = 0.58; P = 0.0006) in plasma and lung tissue. In addition, comet assay presented a significant positive correlation ( r = 0.66; P = 0.007) between cells recovered from target tissue and peripheral blood. Moreover, antioxidant performance was significantly and negatively correlated with DNA damage ( r = −0.50; P = 0.002) in lung tissue. This study indicates that both TAP and comet assay identify increased oxidative stress in CMV rabbits compared with HFOV. Antioxidant performance analyzed by TAP and oxidative DNA damage by comet assay, both in plasma, reflects oxidative stress in the target tissue, which warrants further studies in humans.

scholarly journals GPA Peptide Attenuates Sepsis-Induced Acute Lung Injury in Mice via Inhibiting Oxidative Stress and Pyroptosis of Alveolar Macrophage

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Yukun Liu ◽  
Yongsheng Zhang ◽  
Quanrui Feng ◽  
Qinxin Liu ◽  
Jie Xie ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Alveolar Macrophage ◽  
Inflammatory Cell ◽  
Tissue Injury ◽  
Inflammatory Diseases ◽  
Cecal Ligation ◽  
Regulatory Function ◽  
Protective Effects

Acute lung injury (ALI) has been known to be a devastating form of respiratory infection and an important contributor to mortality in intensive care, due to its lacking of effective treatment. Inflammation, oxidative stress, and pyroptosis are associated with multiple kinds of inflammatory diseases such as ALI. It is commonly accepted that Gly-Pro-Ala (GPA) peptide regulates oxidative stress and pyroptosis in different kinds of inflammatory diseases. Our study is aimed at exploring the regulatory function and protective effects of GPA peptides on ALI. In the current study, the cecal ligation and puncture (CLP) technique was used to evoke sepsis in mice, and GPA peptide was administered intraperitoneally with different concentrations (50, 100, and 150 mg/kg) after CLP. Histopathological changes and the ratio of wet-to-dry in lung were recorded and analyzed. We also investigated the level of oxidative stress, inflammation, and pyroptosis. Results showed that GPA peptide significantly ameliorated CLP-stimulated lung tissue injury, impeded proinflammatory cytokine release, and reduced inflammatory cell infiltration. Additionally, GPA peptide suppressed oxidative stress and caspase-1-dependent pyroptosis in alveolar macrophages. Furthermore, our study showed that the GPA peptide prevents alveolar macrophage from undergoing pyroptosis by attenuating ROS. In conclusion, results demonstrated that GPA peptide has protective effects in CLP-stimulated ALI by inhibiting oxidative stress as well as pyroptosis of alveolar macrophage.

scholarly journals Protective Effect of Corynoline in Sepsis-Induced Acute Lung Injury in Rats via Inhibition of NF-ĸB

2020 ◽  
Vol 15 (11) ◽  
pp. 1934578X2096118
Author(s):  
Min Shu ◽  
Yulu Tang ◽  
Jianzhen Liu
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Protective Effect ◽  
Lung Tissue ◽  
Significant Inhibition ◽  
Tissue Homogenate ◽  
Necrosis Factor Alpha ◽  
Lung Tissue Homogenate ◽  
And Migration

The present study was conducted to determine the effect of corynoline (COR) against sepsis-induced acute lung injury (ALI) in Wistar rats. Results of the study suggested that COR causes significant inhibition of lipid peroxidation (malondialdehyde) together with inhibition of oxidative stress (superoxide dismutase, catalase, glutathione peroxidase, and myeloperoxidase). The level of various proinflammatory (tumor necrosis factor-alpha, interleukin-8, and migration inhibitory factor) was also found to be reduced in COR-treated rats after sepsis. The protective effect of COR was further substantiated by the histopathology of lung tissue, where it improves the architecture of alveolar spaces. In western blot analysis, COR causes significant inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells activation in the lung tissue homogenate. Our results demonstrated that COR was able to prevent the progression of ALI in rats via inhibition of inflammation and oxidative stress.

scholarly journals Effect of penehyclidine hydrochloride on IL-6, TNF-α, HIF- 1α and oxidative stress in lung tissue of young rats with acute lung injury

2020 ◽  
Vol 19 (7) ◽  
pp. 1429-1433
Author(s):  
Jihong Shu ◽  
Zhenjiao Fang ◽  
Xinjun Xiong
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Lung Tissue ◽  
Enzyme Linked Immunosorbent Assay ◽  
High Dose ◽  
Model Group ◽  
Tnf Α ◽  
Penehyclidine Hydrochloride ◽  
And Oxidative Stress

Purpose: To investigate the effect of penehyclidine hydrochloride (PHC) on interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), hypoxia inducible factor-1α (HIF-1α), and oxidative stress levels in lung tissues of acute lung injury (ALI) neonatal rats.Methods: 40 male Sprague-Dawley (SD) rats were assigned to model, low-dose PHC, high-dose PHC, and control groups (n = 10). Levels of IL-6, TNF-α and HIF-1α were evaluated by enzyme-linked immunosorbent assay (ELISA). Pulmonary lesions were determined histologically using H&E staining.Results: The lung tissue levels of IL-6, TNF-α and HIF-1α were significantly higher in model rats than in control rats, and significantly lower in PHC-treated rats than in model group, with decrease in levels as PHC dose increased (p < 0.05). The lung tissue activity of MPO and level of MDA in model rats were significantly higher than those in control rats, but significantly lower in the lung tissues of the two PHC groups than in the model group; decrease in levels occurred as PHC dose increased (p < 0.05).Conclusion: PHC decreases the lung and serum levels of IL-6, TNF-α and HIF-1α in a rat model of ALI, and mitigates pulmonary oxidative stress and lung tissue damage. Thus, penehyclidine hydrochloride may be useful to mitigate ALI-induced damage in patients. However, further studies and clinical trials are required to ascertain this Keywords: Penehyclidine hydrochloride, Alveolar septum, Acute lung injury, Inflammatory cells, IL-6, TNF-α, HIF-1α, Oxidative stress

Sodium houttuyfonate relieves acute lung injury by nano micellar carrier and inhibits mitogen-activated protein kinase and nuclear factor kappa-B activation in mice

2021 ◽  
Vol 11 (5) ◽  
pp. 781-788
Author(s):  
Kai Yang ◽  
Shushu Yan ◽  
Jian Xie ◽  
Fang Xie ◽  
Zhenzhen Zhao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Vascular Permeability ◽  
Delivery System ◽  
Lung Tissue ◽  
Good Effect ◽  
Pulmonary Vascular Permeability ◽  
Cytokine Levels ◽  
And Oxidative Stress

Acute lung injury (ALI) is characterized by increased pulmonary vascular permeability in response to the accumulation of inflammatory cells, release of inflammatory cytokines, and activated oxidative stress. The present study was performed to investigate the effect of sodium houttuyfonate (SH), an extract of Houttuynia cordata, on inflammatory response and oxidative stress in ALI induced by lipopolysaccharides (LPS). Male C57BL/6 mice were randomly allocated to control, LPS, dimethyl sulfoxide (DMSO), and SH groups. The ALI model was established by intratracheal LPS injection. Lung tissue was collected 6 h after LPS injection for histopathological analysis, measurement of wet-to-dry ratio, myeloperoxidase (MPO) and oxidative stress levels, and the p38, jun N-terminal kinase (JNK), extracellular regulated kinase (ERK), and p65 phosphorylation levels. Bronchoalveolar fluid (BALF) was collected for the detection of protein concentration, MPO and cytokine levels. The histopathological test showed that SH significantly alleviates damage to pulmonary tissue. Improved vascular permeability was indicated by reduced BALF protein level and lung wet-to-dry ratio in the SH group. MPO levels were decreased in lung tissue and BALF. Oxidative stress and inflammatory responses were inhibited by SH, as indicated by MDA, SOD and cytokine levels. The MAPK and NF-KB pathways were inhibited as shown by the attenuated phosphorylation of p38, JNK, ERK and p65. Sodium houttuyfonate exhibited a protective role against LPS-induced lung injury through anti-oxidative and anti-inflammatory effects. The MAPK and NF-K B pathways may be inhibited by sodium houttuyfonate. Sodium Houttuynin has a good effect on a variety of acute infectious diseases, but its solubility and stability are insufficient, which limits its efficacy. Nano delivery system can enhance the effective ingredients of traditional Chinese medicine, reduce the toxic and side effects of drugs, and improve their medicinal properties. Therefore, this paper adopts nano delivery system to assist drug use and improve research efficiency.

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 Mucin1 relieves acute lung injury by inhibiting inflammation and oxidative stress

2021 ◽  
Vol 65 (4) ◽  
Author(s):  
Chunlin Ye ◽  
Bin Xu ◽  
Jie Yang ◽  
Yunkun Liu ◽  
Zhikai Zeng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Respiratory Distress ◽  
Signaling Pathway ◽  
Lung Tissue ◽  
Inflammatory Factors ◽  
Mouse Lung ◽  
Muc1 Gene ◽  
And Oxidative Stress

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a kind of diffuse inflammatory injury caused by various factors, characterized by respiratory distress and progressive hypoxemia. It is a common clinical critical illness. The aim of this study was to investigate the effect and mechanism of the Mucin1 (MUC1) gene and its recombinant protein on lipopolysaccharide (LPS)-induced ALI/ARDS. We cultured human alveolar epithelial cell line (BEAS-2B) and used MUC1 overexpression lentivirus to detect the effect of MUC1 gene on BEAS-2B cells. In addition, we used LPS to induce ALI/ARDS in C57/BL6 mice and use hematoxylin and eosin (H&E) staining to verify the effect of their modeling. Recombinant MUC1 protein was injected subcutaneously into mice. We examined the effect of MUC1 on ALI/ARDS in mice by detecting the expression of inflammatory factors and oxidative stress molecules in mouse lung tissue, bronchoalveolar lavage fluid (BALF) and serum. Overexpression of MUC1 effectively ameliorated LPS-induced damage to BEAS-2B cells. Results of H&E staining indicate that LPS successfully induced ALI/ARDS in mice and MUC1 attenuated lung injury. MUC1 also reduced the expression of inflammatory factors (IL-1β, TNF-α, IL-6 and IL-8) and oxidative stress levels in mice. In addition, LPS results in an increase in the activity of the TLR4/NF-κB signaling pathway in mice, whereas MUC1 decreased the expression of the TLR4/NF-κB signaling pathway. MUC1 inhibited the activity of TLR4/NF-κB signaling pathway and reduced the level of inflammation and oxidative stress in lung tissue of ALI mice.

scholarly journals Tanreqing Inhibits LPS-Induced Acute Lung Injury In Vivo and In Vitro Through Downregulating STING Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Yu-Qiong He ◽  
Can-Can Zhou ◽  
Jiu-Ling Deng ◽  
Liang Wang ◽  
Wan-Sheng Chen
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Signaling Pathway ◽  
Inflammatory Responses ◽  
Lung Edema ◽  
Protective Effects ◽  
And Oxidative Stress

Acute lung injury (ALI) is a common life-threatening lung disease, which is mostly associated with severe inflammatory responses and oxidative stress. Tanreqing injection (TRQ), a Chinese patent medicine, is clinically used for respiratory-related diseases. However, the effects and action mechanism of TRQ on ALI are still unclear. Recently, STING as a cytoplasmic DNA sensor has been found to be related to the progress of ALI. Here, we showed that TRQ significantly inhibited LPS-induced lung histological change, lung edema, and inflammatory cell infiltration. Moreover, TRQ markedly reduced inflammatory mediators release (TNF-α, IL-6, IL-1β, and IFN-β). Furthermore, TRQ also alleviated oxidative stress, manifested by increased SOD and GSH activities and decreased 4-HNE, MDA, LDH, and ROS activities. In addition, we further found that TRQ significantly prevented cGAS, STING, P-TBK, P-P65, P-IRF3, and P-IκBα expression in ALI mice. And we also confirmed that TRQ could inhibit mtDNA release and suppress signaling pathway mediated by STING in vitro. Importantly, the addition of STING agonist DMXAA dramatically abolished the protective effects of TRQ. Taken together, this study indicated that TRQ alleviated LPS-induced ALI and inhibited inflammatory responses and oxidative stress through STING signaling pathway.

scholarly journals The Roles of Autophagy in Acute Lung Injury Induced by Myocardial Ischemia Reperfusion in Diabetic Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Liying Zhan ◽  
Yuan Zhang ◽  
Wating Su ◽  
Qiongxia Zhang ◽  
Rong Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Myocardial Ischemia ◽  
Lung Injury ◽  
Ischemia Reperfusion ◽  
Diabetic Rats ◽  
Lung Injury Score ◽  
Sod Activity ◽  
Autophagy Inhibitor ◽  
Myocardial Ischemia Reperfusion

Patients with diabetes are vulnerable to myocardial ischemia reperfusion (IR) injury, which may also induce acute lung injury (ALI) due to overaccumulation of reactive oxygen species (ROS) and inflammation cytokine in circulation. Despite autophagy plays a significant role in diabetes and pulmonary IR injury, the role of autophagy in ALI secondary to myocardial IR in diabetes remains largely elusive. We aimed to investigate pulmonary autophagy status and its roles in oxidative stress and inflammation reaction in lung tissues from diabetic rats subjected to myocardial IR. Control or diabetic rats were either treated with or without autophagy inducer rapamycin (Rap) or autophagy inhibitor 3-methyladenine (3-MA) before myocardial IR, which was achieved by occluding the left anterior descending coronary artery for 30 min and followed by reperfusion for 120 min. Diabetic rats subjected to myocardial IR showed more serious ALI with higher lung injury score and WET/DRY ratio and lower PaO2 as compared with control rats, accompanied with impaired autophagy indicated by reduced LC-3II/LC-3I ratio and Beclin-1 expression, decreased superoxide dismutase (SOD) activity, and increased 15-F2t-Isoprostane formation in lung tissues, as well as increased levels of leukocyte count and proinflammatory cytokines in BAL fluid. Improving autophagy with Rap significantly attenuated all these changes, but the autophagy inhibitor 3-MA exhibited adverse or opposite effects as Rap. In conclusion, diabetic lungs are more vulnerable to myocardial IR, which are involved in impaired autophagy. Improving autophagy could attenuate ALI induced by myocardial IR in diabetic rats, possibly through inhibiting inflammatory reaction and oxidative stress.

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