Acetylated Polysaccharides From Pleurotus geesteranus Alleviate Lung Injury Via Regulating NF-κB Signal Pathway

The present work investigated the anti-inflammatory, antioxidant, and lung protection effects of acetylated Pleurotus geesteranus polysaccharides (AcPPS) on acute lung injury (ALI) mice. The acetylation of AcPPS was successfully shown by the peaks of 1737 cm−1 and 1249 cm−1 by FTIR. The animal experiments demonstrated that lung damage can be induced by zymosan. However, the supplementation of AcPPS had potential effects on reducing lung index, remitting inflammatory symptoms (TNF-α, IL-1β, and IL-6), inhibiting NF-κB signal pathway based on up-regulating the level of IκBα and down-regulating p-IκBα level by Western blotting and immunofluorescence assay, preventing oxidative stress (ROS, SOD, GSH-Px, CAT, T-AOC, and MDA), reducing lipid accumulation (TC, TG, LDL-C, HDL-C, and VLDL-C), and alleviating lung functions by histopathologic observation. These results demonstrated that AcPPS might be suitable for natural food for prevention or remission in ALI.

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Protective effects of hydrogen against irradiation

Current Pharmaceutical Design ◽

10.2174/1381612827666210119103545 ◽

2021 ◽

Vol 27 ◽

Author(s):

Yasuhiro Terasaki ◽

Mika Terasaki ◽

Akira Shimizu

Keyword(s):

Oxidative Stress ◽

Lung Injury ◽

Cultured Cells ◽

Animal Experiments ◽

Lung Epithelial Cells ◽

Lung Damage ◽

Protective Effects ◽

Chronic Radiation ◽

Radiation Induced ◽

Reactive Oxidants

: Radiation-induced lung injury is characterized by an acute pneumonia phase followed by a fibrotic phase. At the time of irradiation, a rapid, short-lived burst of reactive oxygen species (ROS) such as hydroxyl radicals (•OH) occurs, but chronic radiation-induced lung injury may occur due to excess ROS such as H2O2 , O2•− , ONOO− , and •OH. Molecular hydrogen (H2 ) is an efficient antioxidant that quickly diffuses cell membranes, reduces ROS such as •OH and ONOO− , and suppresses damage caused by oxidative stress in various organs. In 2011, through the evaluation of electron-spin resonance and fluorescent indicator signals, we had reported that H2 can eliminate •OH and can protect against oxidative stress-related apoptotic damage induced by irradiation of cultured lung epithelial cells. We had explored for the first time the radioprotective effects of H2 treatment on acute and chronic radiation-induced lung damage in mice by inhaled H2 gas (for acute) and imbibed H2 -enriched water (for chronic). Thus, we had proposed that H2 be considered a potential radioprotective agent. Recent publications have shown that H2 directly neutralizes highly reactive oxidants and indirectly reduces oxidative stress by regulating the expression of various genes. By regulating gene expression, H2 functions as an anti-inflammatory and anti-apoptotic molecule and promotes energy metabolism. The increased evidence obtained from cultured cells or animal experiments reveal a putative place for H2 treatment and its radioprotective effect clinically. This review focuses on major scientific advances of in the treatment of H2 as a new class of radioprotective agents.

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Remote Inflammatory Preconditioning Alleviates Lipopolysaccharide-Induced Acute Lung Injury via Inhibition of Intrinsic Apoptosis in Rats

Journal of Immunology Research ◽

10.1155/2021/1125199 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Yong Liu ◽

Jiahang Xu ◽

Liang Zhao ◽

Jing Cheng ◽

Baojun Chen

Keyword(s):

Oxidative Stress ◽

Acute Lung Injury ◽

Lung Injury ◽

Animal Experiments ◽

Intrinsic Apoptosis ◽

Sprague Dawley ◽

Sod Activity ◽

Lung Protection ◽

Sprague Dawley Rats ◽

The Right

Background. Acute lung injury (ALI) always leads to severe inflammation. As inflammation and oxidative stress are the common pathological basis of endotoxin-induced inflammatory injury and ischemic reperfusion injury (IRI), we speculate that remote ischemic preconditioning (RIPC) can be protective for ALI when used as remote inflammatory preconditioning (RInPC). Method. A total of 21 Sprague-Dawley rats were used for the animal experiments. Eighteen rats were equally and randomly divided into the control (NS injection), LPS (LPS injection), and RInPC groups. The RInPC was performed prior to the LPS injection via tourniquet blockage of blood flow to the right hind limb and adopted three cycles of 5 min tying followed by 5 min untying. Animals were sacrificed 24 hours later. There were 2 rats in the LPS group and 1 in the RInPC group who died before the end of the experiment. Supplementary experiments in the LPS and RInPC groups were conducted to ensure that 6 animals in each group reached the end of the experiment. Results. In the present study, we demonstrated that the RInPC significantly attenuated the LPS-induced ALI in rats. Apoptotic cells were reduced significantly by the RInPC, with the simultaneous improvement of apoptosis-related proteins. Reduction of MPO and MDA and increasing of SOD activity were found significantly improved by the RInPC. Increasing of TNF-α, IL-1β, and IL-6 induced by the LPS was inhibited, while IL-10 was significantly increased by RInPC, compared to the LPS group. Conclusion. RInPC could inhibit inflammation and attenuate oxidative stress, thereby reducing intrinsic apoptosis and providing lung protection in the LPS-induced ALI in rats.

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Effects of melatonin in an experimental model of ventilator-induced lung injury

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.90211.2008 ◽

2008 ◽

Vol 295 (5) ◽

pp. L820-L827 ◽

Cited By ~ 24

Author(s):

Paula R. Pedreira ◽

Emilio García-Prieto ◽

Diego Parra ◽

Aurora Astudillo ◽

Elena Diaz ◽

...

Keyword(s):

Oxidative Stress ◽

Matrix Metalloproteinases ◽

Lung Injury ◽

Weight Ratio ◽

Peak Inspiratory Pressure ◽

Lung Damage ◽

Inspiratory Pressure ◽

Ventilator Induced Lung Injury ◽

Tnf Α ◽

Anti Inflammatory

Melatonin is a free radical scavenger and a broad-spectrum antioxidant and has well-documented immunomodulatory effects. We studied the effects of this hormone on lung damage, oxidative stress, and inflammation in a model of ventilator-induced lung injury (VILI), using 8- to 12-wk-old Swiss mice ( n = 48). Animals were randomized into three experimental groups: control (not ventilated); low-pressure ventilation [peak inspiratory pressure 15 cmH2O, positive end-expiratory pressure (PEEP) 2 cmH2O], and high-pressure ventilation (peak inspiratory pressure 25 cmH2O, PEEP 0 cmH2O). Each group was divided into two subgroups: eight animals were treated with melatonin (10 mg/kg ip, 30 min before the onset of ventilation) and the remaining eight with vehicle. After 2 h of ventilation, lung injury was evaluated by gas exchange, wet-to-dry weight ratio, and histological analysis. Levels of malondialdehyde, glutathione peroxidase, interleukins IL-1β, IL-6, TNF-α, and IL-10, and matrix metalloproteinases 2 and 9 in lung tissue were measured as indicators of oxidation status, pro-/anti-inflammatory cytokines, and matrix turnover, respectively. Ventilation with high pressures induced severe lung damage and release of TNF-α, IL-6, and matrix metalloproteinase-9. Treatment with melatonin improved oxygenation and decreased histological lung injury but significantly increased oxidative stress quantified by malondialdehyde levels. There were no differences in TNF-α, IL-1β, IL-6, or matrix metalloproteinases caused by melatonin treatment, but IL-10 levels were significantly higher in treated animals. These results suggest that melatonin decreases VILI by increasing the anti-inflammatory response despite an unexpected increase in oxidative stress.

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Elevated plasma levels of soluble TNF receptors are associated with morbidity and mortality in patients with acute lung injury

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00302.2004 ◽

2005 ◽

Vol 288 (3) ◽

pp. L426-L431 ◽

Cited By ~ 128

Author(s):

Polly E. Parsons ◽

Michael A. Matthay ◽

Lorraine B. Ware ◽

Mark D. Eisner

Keyword(s):

Lung Injury ◽

Plasma Levels ◽

A549 Cells ◽

Multicenter Trial ◽

Morbidity And Mortality ◽

Lung Protective Ventilation ◽

Single Center ◽

Lung Protection ◽

Tnf Α

Ventilator-induced lung injury (VILI) is an inflammatory process that can be attenuated by lung protective ventilation strategies. Our objectives to further investigate the pathogenesis of ALI and VILI and the mechanism of lung protection in these syndromes were: 1) to determine if plasma measurements of soluble TNF receptor I (sTNFRI) and II (sTNFRII) would predict the development of ALI and mortality in a small single center trial; 2) to test the predictive value of these markers and of TNF-α in a larger, broader group of patients with ALI; 3) to test the hypothesis that low tidal volume ventilation (LTVV) would be associated with a decrease in plasma levels of TNF-α, sTNFRI, and sTNFRII. In the single center study, sTNFRI and II levels were higher in patients at risk for and with ALI, but they did not predict the development of the syndrome. In the multicenter trial sTNFRI and II were strongly associated with mortality (OR 5.76/1 log10 increment in receptor level; 95% CI 2.63–12.6 and OR 2.58; 95% CI 1.05–6.31, respectively) and morbidity measured as fewer nonpulmonary organ failure-free and ventilator-free days. The LTVV strategy was associated with an attenuation of plasma sTNFRI levels. In vitro, stimulated A549 cells release sTNFRI but not sTNRFII. In conclusion, plasma levels of sTNFRI and II can serve as biomarkers for morbidity and mortality in patients with ALI. Furthermore, LTVV is associated with a specific decrease in sTNFRI levels. This suggests that one beneficial effect of LTVV may be to attenuate alveolar epithelial injury.

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Huangkui Capsule Attenuates Lipopolysaccharide-Induced Acute Lung Injury and Macrophage Activation by Suppressing Inflammation and Oxidative Stress in Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/6626483 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Jinfang Deng ◽

Zhenpeng He ◽

Xiuru Li ◽

Wei Chen ◽

Ziwen Yu ◽

...

Keyword(s):

Oxidative Stress ◽

Acute Lung Injury ◽

Lung Injury ◽

Macrophage Activation ◽

Neutrophil Infiltration ◽

Raw 264.7 Cells ◽

Raw 264.7 ◽

Myeloperoxidase Activity ◽

Tnf Α ◽

And Oxidative Stress

Background. Huangkui capsule (HKC) comprises the total flavonoid extract of flowers of Abelmoschus manihot (L.) Medicus. This study aimed to explore the effects of HKC on lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice and LPS-stimulated RAW 264.7 cells. Methods. Enzyme-linked immunosorbent assay, histopathology, spectrophotometry, and quantitative real-time polymerase chain reaction were used for the assessments. Statistical analysis was performed using a one-way analysis of variance. Results. LPS significantly increased lung inflammation, neutrophil infiltration, and oxidative stress and downregulated lung miR-451 expression. Treatment with HKC dramatically attenuated the lung wet/dry weight ratio, reduced the total cell count in the bronchoalveolar lavage fluid (BALF), and inhibited myeloperoxidase activity in the lung tissues 24 h after LPS challenge. Histopathological analysis demonstrated that HKC attenuated LPS-induced tissue oedema and neutrophil infiltration in the lung tissues. Additionally, the concentrations of tumour necrosis factor- (TNF-) α and interleukin- (IL-) 6 in BALF and IL-6 in the plasma reduced after HKC administration. Moreover, HKC could enhance glutathione peroxidase and catalase activities and upregulate the expression of miR-451 in the lung tissues. In vitro experiments revealed that HKC inhibited the production of nitric oxide, TNF-α, and IL-6 in LPS-induced RAW 264.7 cells and mouse primary peritoneal macrophages. Additionally, HKC downregulated LPS-induced transcription of TNF-α and IL-6 in RAW 264.7 cells. Conclusions. These findings suggest that HKC has anti-inflammatory and antioxidative effects that may protect mice against LPS-induced ALI and macrophage activation.

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Lipoxin A4 attenuates LPS-induced acute lung injury via activation of the ACE2-Ang-(1-7)-Mas axis

Innate Immunity ◽

10.1177/1753425918785008 ◽

2018 ◽

Vol 24 (5) ◽

pp. 285-296 ◽

Cited By ~ 6

Author(s):

Qiong-Feng Chen ◽

Xiao-Dong Kuang ◽

Qi-Feng Yuan ◽

Hua Hao ◽

Ting Zhang ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Direct Evidence ◽

Signal Pathway ◽

Oxygen Species ◽

Angiotensin I ◽

Lipoxin A4 ◽

Mas Receptor ◽

Angiotensin I Converting Enzyme ◽

Tnf Α

Previous studies have reported that lipoxin A4 (LXA4) and the angiotensin I-converting enzyme 2 (ACE2), angiotensin-(1-7) [Ang-(1-7)], and its receptor Mas [ACE2-Ang-(1-7)-Mas] axis play important protective roles in acute lung injury (ALI). However, there is still no direct evidence of LXA4-mediated protection via the ACE2-Ang-(1-7)-Mas axis during ALI. This work was performed using an LPS-induced ALI mouse model and the data indicated the following. First, the animal model was established successfully and LXA4 ameliorated LPS-induced ALI. Second, LXA4 could increase the concentration and activity of ACE2 and the levels of Ang-(1-7) and Mas markedly. Third, LXA4 decreased the levels of TNF-α, IL-1β, and reactive oxygen species while increasing IL-10 levels. Fourth, LXA4 inhibited the activation of the NF-κB signal pathway and repressed the degradation of inhibitor of NF-κB, the phosphorylation of NF-κB, and the translocation of NF-κB. Finally, and more importantly, BOC-2 (LXA4 receptor inhibitor), MLN-4760 (ACE2 inhibitor), and A779 (Mas receptor antagonist) were found to reverse all of the effects of LXA4. Our data provide evidence that LXA4 protects the lung from ALI through regulation of the ACE2-Ang-(1-7)-Mas axis.

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miR-20a attenuates acute lung injury in septic rats via targeting TLR4

10.22514/sv.2021.097 ◽

2021 ◽

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Inflammatory Response ◽

Lung Tissue ◽

Cecal Ligation ◽

Normal Group ◽

Lung Damage ◽

Luciferase Reporter ◽

Arterial Bleeding ◽

Tnf Α

Background: Sepsis is most likely to cause lung damage in patients, and the detection rate and mortality rate are high. Here, we investigated the expression of miR-20a in sepsis-induced acute lung injury (ALI) rats and its effect on inflammatory response, and reveal its possible molecular mechanism. Method: The model of acute lung injury caused by sepsis in rats was established by cecal ligation and puncture. The expression of miR-20a in lung tissue was determined by RT-qPCR. Acute lung injury rats were injected with 5 nmol miR-20a agomir or agomir NC every day for 3 days. Rats were sacrificed by arterial bleeding and lung tissues were removed. Serum interleukin (IL) -1β, IL-6, and tumor necrosis factor alpha (TNF-α) were detected by ELISA. HE staining was used to observe the pathology of lung tissue and calculate the pathological score of lung injury. Western blot to determine the level of TLR4 and nuclear transcription factor κB p65 (NF-κB p65) protein in lung tissue. The luciferase reporter assay was used to verify the binding effect of miR-20a on the 3 non-coding TLR4. Results: We found that compared with that in Normal group, the expression of miR-20a in lung tissues of rats with ALI was decreased (p < 0.05). In miR-20a agomir group, the plasma level of IL-1β, IL-6, and TNF-α was significantly lower than that in agomir NC group and ALI group (p < 0.05), while higher than those in Normal group (p < 0.05). The HE staining results showed that the pathological score of lung injury in rats in miR-20a agomir group was lower than that of agomir NC group and ALI group (p < 0.05). Compared with agomir NC group and ALI group, the expression of TLR4 and NF-κB p65 in miR-20a agomir group was decreased (p < 0.01). The luciferase reporting experiment confirmed that TLR4 was a target gene of miR-20a. Conclusion: To sum up, miR-20a exerts a protective effect on sepsis-induced ALI rats through its anti-inflammatory effect. The targeting of TLR4 by miR-20a may be an effective method to reduce the inflammatory response in sepsis-induced ALI.

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Spiraea prunifolia var. simpliciflora Attenuates Oxidative Stress and Inflammatory Responses in a Murine Model of Lipopolysaccharide-Induced Acute Lung Injury and TNF-α-Stimulated NCI-H292 Cells

Antioxidants ◽

10.3390/antiox9030198 ◽

2020 ◽

Vol 9 (3) ◽

pp. 198 ◽

Cited By ~ 1

Author(s):

Ba-Wool Lee ◽

Ji-Hye Ha ◽

Han-Gyo Shin ◽

Seong-Hun Jeong ◽

Da-Bin Jeon ◽

...

Keyword(s):

Oxidative Stress ◽

Acute Lung Injury ◽

Lung Injury ◽

Nuclear Translocation ◽

Inflammatory Responses ◽

Therapeutic Potential ◽

Herbal Remedy ◽

Related Factor ◽

Nuclear Factor ◽

Tnf Α

Spiraea prunifolia var. simpliciflora (SP) is traditionally used as an herbal remedy to treat fever, malaria, and emesis. This study aimed to evaluate the anti-oxidative and anti-inflammatory properties of the methanol extract of SP leaves in tumor necrosis factor (TNF)-α-stimulated NCI-H292 cells and in a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. SP decreased the number of inflammatory cells and the levels of TNF-α, interleukin (IL)-1β, and IL-6 in the bronchoalveolar lavage fluid, and inflammatory cell infiltration in the lung tissues of SP-treated mice. In addition, SP significantly suppressed the mRNA and protein levels of TNF-α, IL-1β, and IL-6 in TNF-α-stimulated NCI-H292 cells. SP significantly suppressed the phosphorylation of the mitogen-activated protein kinases (MAPKs) and p65-nuclear factor-kappa B (NF-κB) in LPS-induced ALI mice and TNF-α-stimulated NCI-H292 cells. SP treatment enhanced the nuclear translocation of nuclear factor erythroid 2-related factor (Nrf2) with upregulated antioxidant enzymes and suppressed reactive oxygen species (ROS)-mediated oxidative stress in the lung tissues of LPS-induced ALI model and TNF-α-stimulated NCI-H292 cells. Collectively, SP effectively inhibited airway inflammation and ROS-mediated oxidative stress, which was closely related to its ability to induce activation of Nrf2 and inhibit the phosphorylation of MAPKs and NF-κB. These findings suggest that SP has therapeutic potential for the treatment of ALI.

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Resistance of hypotransferrinemic mice to hyperoxia-induced lung injury

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1999.277.6.l1214 ◽

1999 ◽

Vol 277 (6) ◽

pp. L1214-L1223 ◽

Cited By ~ 6

Author(s):

Funmei Yang ◽

Jacqueline J. Coalson ◽

Heather H. Bobb ◽

Jacqueline D. Carter ◽

Jameela Banu ◽

...

Keyword(s):

Oxidative Stress ◽

Lung Injury ◽

Alveolar Macrophages ◽

Lung Damage ◽

Mouse Lung ◽

Heme Oxygenase 1 ◽

Wild Type ◽

Chronic Pulmonary Diseases ◽

Hyperoxic Lung Injury ◽

Key Participants

Oxidative stress plays a central role in the pathogenesis of acute and chronic pulmonary diseases. Safe sequestration of iron, which participates in the formation of the hydroxyl radical, is crucial in the lung's defense. We used a mouse line defective in the major iron transport protein transferrin to investigate the effect of aberrant iron metabolism on the lung's defense against oxidative injury. The tolerance to hyperoxic lung injury was greater in the hypotransferrinemic than in wild-type mice as documented by histopathology and biochemical indexes for lung damage. There was no increase in the levels of intracellular antioxidants, inflammatory cytokines, and heme oxygenase-1 in the hypotransferrinemic mouse lung compared with those in wild-type mice. However, there were elevated expressions of ferritin and lactoferrin in the lung of hypotransferrinemic mice, especially in the alveolar macrophages. Our results suggest that pulmonary lactoferrin and ferritin protect animals against oxidative stress, most likely via their capacity to sequester iron, and that alveolar macrophages are the key participants in iron detoxification in the lower respiratory tract.

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Cromolyn Sodium Attenuates Paraquat-Induced Lung Injury by Modulation of Proinflammatory Cytokines

Drug Research ◽

10.1055/s-0042-123711 ◽

2017 ◽

Vol 67 (05) ◽

pp. 283-288 ◽

Cited By ~ 13

Author(s):

Amir Larki Harchegani ◽

Ali Asghar Hemmati ◽

Amir Nili-Ahmadabadi ◽

Borhan Darabi ◽

Somayeh Shabib

Keyword(s):

Lung Injury ◽

Oral Dose ◽

Proinflammatory Cytokines ◽

Cromolyn Sodium ◽

Lung Damage ◽

Serum Samples ◽

Best Response ◽

Tnf Α ◽

Group 3 ◽

Group 1

AbstractThe current study aimed to investigate the effects of Cromolyn Sodium (CS) on proinflammatory cytokines in Paraquat (PQ)-induced lung damage in rat. Animals were randomly divided into 5 groups. Group 1 and 2 received nebulized vehicle and CS (8 mg/kg) for 3 consecutive weeks, respectively. Group 3 was treated with single oral dose of PQ (40 mg/kg). Groups 4 and 5 were PQ groups which received nebulized CS (6 and 8 mg/kg/day, respectively) from 1 week before to 2 weeks after PQ administration. Finally, the animals were scarified and the changes of hydroxyproline (HP) and histology were evaluated in lung tissue. In addition, IL-1β, TNF-α and IL-8 levels were determined in serum samples. The results showed that lung HP level as well as IL-1β, TNF-α and IL-8 were significantly lower in the CS treated rats as compared to PQ group. The best response, however, was observed with the 8 mg/kg of CS as confirmed by histology findings. This study suggests that CS may prevent progression of PQ-induced lung damage by decreasing of inflammatory cytokines.

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