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

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.

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

Natural Product Communications ◽

10.1177/1934578x20961188 ◽

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.

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

Materials Express ◽

10.1166/mex.2021.1979 ◽

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.

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

Acta Biochimica Polonica ◽

10.18388/abp.2016_1296 ◽

2016 ◽

Vol 64 (1) ◽

Cited By ~ 7

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.

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

Journal of Innovative Optical Health Sciences ◽

10.1142/s179354581350017x ◽

2013 ◽

Vol 06 (03) ◽

pp. 1350017 ◽

Cited By ~ 5

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.

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Mucin1 relieves acute lung injury by inhibiting inflammation and oxidative stress

European Journal of Histochemistry ◽

10.4081/ejh.2021.3331 ◽

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.

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

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v19i7.14 ◽

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

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Interactive effects of mechanical ventilation, inhaled nitric oxide and oxidative stress in acute lung injury

Respiratory Physiology & Neurobiology ◽

10.1016/j.resp.2013.10.008 ◽

2014 ◽

Vol 190 ◽

pp. 118-123 ◽

Cited By ~ 6

Author(s):

Carlos Fernando Ronchi ◽

Ana Lucia Anjos Ferreira ◽

Fabio Joly Campos ◽

Cilmery Suemi Kurokawa ◽

Mario Ferreira Carpi ◽

...

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Mechanical Ventilation ◽

Acute Lung Injury ◽

Lung Injury ◽

Inhaled Nitric Oxide ◽

Interactive Effects ◽

And Oxidative Stress

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Dietary Antioxidants Significantly Attenuate Hyperoxia-Induced Acute Inflammatory Lung Injury by Enhancing Macrophage Function via Reducing the Accumulation of Airway HMGB1

International Journal of Molecular Sciences ◽

10.3390/ijms21030977 ◽

2020 ◽

Vol 21 (3) ◽

pp. 977 ◽

Cited By ~ 9

Author(s):

Vivek Patel ◽

Katelyn Dial ◽

Jiaqi Wu ◽

Alex G. Gauthier ◽

Wenjun Wu ◽

...

Keyword(s):

Oxidative Stress ◽

Mechanical Ventilation ◽

Ascorbic Acid ◽

Acute Lung Injury ◽

Lung Injury ◽

Nitrosative Stress ◽

Prolonged Exposure ◽

Dietary Antioxidants ◽

Oxidative And Nitrosative Stress ◽

Macrophage Function

Mechanical ventilation with hyperoxia is the major supportive measure to treat patients with acute lung injury and acute respiratory distress syndrome (ARDS). However, prolonged exposure to hyperoxia can induce oxidative inflammatory lung injury. Previously, we have shown that high levels of airway high-mobility group box 1 protein (HMGB1) mediate hyperoxia-induced acute lung injury (HALI). Using both ascorbic acid (AA, also known as vitamin C) and sulforaphane (SFN), an inducer of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), we tested the hypothesis that dietary antioxidants can mitigate HALI by ameliorating HMGB1-compromised macrophage function in phagocytosis by attenuating hyperoxia-induced extracellular HMGB1 accumulation. Our results indicated that SFN, which has been shown to attenute HALI in mice exposed to hyperoxia, dose-dependently restored hyperoxia-compromised macrophage function in phagocytosis (75.9 ± 3.5% in 0.33 µM SFN versus 50.7 ± 1.8% in dimethyl sulfoxide (DMSO) control, p < 0.05) by reducing oxidative stress and HMGB1 release from cultured macrophages (47.7 ± 14.7% in 0.33 µM SFN versus 93.1 ± 14.6% in DMSO control, p < 0.05). Previously, we have shown that AA enhances hyperoxic macrophage functions by reducing hyperoxia-induced HMGB1 release. Using a mouse model of HALI, we determined the effects of AA on hyperoxia-induced inflammatory lung injury. The i.p. administration of 50 mg/kg of AA to mice exposed to 72 h of ≥98% O2 significantly decreased hyperoxia-induced oxidative and nitrosative stress in mouse lungs. There was a significant decrease in the levels of airway HMGB1 (43.3 ± 12.2% in 50 mg/kg AA versus 96.7 ± 9.39% in hyperoxic control, p < 0.05), leukocyte infiltration (60.39 ± 4.137% leukocytes numbers in 50 mg/kg AA versus 100 ± 5.82% in hyperoxic control, p < 0.05) and improved lung integrity in mice treated with AA. Our study is the first to report that the dietary antioxidants, ascorbic acid and sulforaphane, ameliorate HALI and attenuate hyperoxia-induced macrophage dysfunction through an HMGB1-mediated pathway. Thus, dietary antioxidants could be used as potential treatments for oxidative-stress-induced acute inflammatory lung injury in patients receiving mechanical ventilation.

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Effects of ketamine, propofol, and ketofol on proinflammatory cytokines and markers of oxidative stress in a rat model of endotoxemia-induced acute lung injury.

Acta Biochimica Polonica ◽

10.18388/abp.2013_2006 ◽

2013 ◽

Vol 60 (3) ◽

Cited By ~ 25

Author(s):

Derya Gokcinar ◽

Volkan Ergin ◽

Ahmet Cumaoglu ◽

Adnan Menevse ◽

Aysel Aricioglu

Keyword(s):

Oxidative Stress ◽

Lipid Peroxidation ◽

Acute Lung Injury ◽

Lung Injury ◽

Lung Tissue ◽

Rat Model ◽

Nitrite Level ◽

Tnf Α ◽

Markers Of Oxidative Stress ◽

Pro Inflammatory Cytokines

Intravenous lipopolysaccharide (LPS) leads to acute lung injury (ALI) in rats. The purpose of this study was to examine the anti-inflammatory and antioxidant efficacy of ketamine, propofol, and ketofol in a rat model of ALI. We induced ALI in rats via intravenous injection of LPS (15 mg kg(-1)). The animals were randomly separated into five groups: control, LPS only, LPS + ketamine (10 mg·kg(-1)·h(-1)), LPS + propofol (10 mg·kg(-1)·h(-1)), LPS + ketofol (5 mg·kg(-1)·h(-1) ketamine + 5 mg·kg(-1)·h(-1) propofol). LPS resulted in an increase in the release of pro-inflammatory cytokines, mRNA expression related with inflammation, production of nitric oxide, and lipid peroxidation. Ketamine prevented the increase in markers of oxidative stress and inflammation mediators, both in plasma and lung tissue. Propofol decreased the levels of cytokines in plasma and lung tissue, whereas it had no effect on the IL-1-beta level in lung tissue. Ketamine downregulated mediators of lung tissue inflammation and reduced the level of circulating cytokines and protected lung tissue against lipid peroxidation. Ketofol decreased the level of TNF-α and IL-1β in plasma, as well as expression of cyclooxygenase-2 mRNA and the nitrate/nitrite level in lung tissue. The results of this investigation support the hypothesis that ketamine may be effective in preventing ALI.

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