scholarly journals Friend or Foe? The Roles of Antioxidants in Acute Lung Injury

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1956
Author(s):  
Yang Liu ◽  
Shujun Zhou ◽  
Du Xiang ◽  
Lingao Ju ◽  
Dexin Shen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Organ Injury ◽  
Oxygen Species ◽  
Pulmonary Injury ◽  
Physiological Concentration ◽  
Mitochondrial Oxidative Stress ◽  
Extra Pulmonary

Acute lung injury (ALI) is an acute hypoxic respiratory insufficiency caused by various intra- and extra-pulmonary injury factors. The oxidative stress caused by excessive reactive oxygen species (ROS) produced in the lungs plays an important role in the pathogenesis of ALI. ROS is a “double-edged sword”, which is widely involved in signal transduction and the life process of cells at a physiological concentration. However, excessive ROS can cause mitochondrial oxidative stress, leading to the occurrence of various diseases. It is well-known that antioxidants can alleviate ALI by scavenging ROS. Nevertheless, more and more studies found that antioxidants have no significant effect on severe organ injury, and may even aggravate organ injury and reduce the survival rate of patients. Our study introduces the application of antioxidants in ALI, and explore the mechanisms of antioxidants failure in various diseases including it.

scholarly journals Chrysosplenol D protects mice against LPS-induced acute lung injury by inhibiting oxidative stress, inflammation, and apoptosis via TLR4-MAPKs/NF-κB signaling pathways

2021 ◽  
pp. 175342592110510
Author(s):  
Qinqin Zhang ◽  
Aozi Feng ◽  
Mengnan Zeng ◽  
Beibei Zhang ◽  
Jingya Shi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Signaling Pathways ◽  
Caspase 3 ◽  
Mrna Levels ◽  
Oxygen Species ◽  
Caspase 9 ◽  
Hematoxylin Eosin

This study investigated the effect and mechanism of chrysosplenol D (CD) on LPS-induced acute lung injury in mice. Histological changes in the lungs were measured by hematoxylin-eosin staining. The levels of IL-6, IL-1β, and TNF-α in the bronchoalveolar lavage fluid were detected by ELISA. The levels of oxidative stress were detected by the cuvette assay. Immune cells in peripheral blood, the levels of reactive oxygen species, and apoptosis of primary lung cells were detected by flow cytometry. The mRNA levels of TLR4, MyD88, IL-1β, and NLRP3 were measured by quantitative real-time polymerase chain reaction. The levels of proteins in apoptosis and the TLR4-MAPKs/NF-κB signaling pathways were detected by Western blot. Hematoxylin-eosin staining showed that CD could improve lung injury; decrease the levels of inflammatory factors, oxidative stress, reactive oxygen species, and cell apoptosis; and regulate the immune system. Moreover, CD could down-regulate the mRNA levels of TLR4, MyD88, NLRP3, and IL-1β in lung, and the protein levels of Keap-1, Cleaved-Caspase-3/Caspase-3, Cleaved-Caspase-9/Caspase-9, TLR4, MyD88, p-ERK/ERK, p-JNK/JNK, p-p38/p38, p-p65/p65, NLRP3, and IL-1β, and up-regulated the levels of Bcl-2/Bax, p-Nrf2/Nrf2, and HO-1. The results suggested that CD could protect mice against LPS-induced acute lung injury by inhibiting oxidative stress, inflammation, and apoptosis via the TLR4-MAPKs/NF-κB signaling pathways.

scholarly journals Alda-1 Attenuates Hyperoxia-Induced Acute Lung Injury in Mice

2021 ◽  
Vol 11 ◽  
Author(s):  
Sahebgowda Sidramagowda Patil ◽  
Helena Hernández-Cuervo ◽  
Jutaro Fukumoto ◽  
Sudarshan Krishnamurthy ◽  
Muling Lin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Immune Cell ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
High Concentration ◽  
Associated Proteins ◽  
Alveolar Permeability

Acute lung injury (ALI), a milder form of acute respiratory distress syndrome (ARDS), is a leading cause of mortality in older adults with an increasing prevalence. Oxygen therapy, is a common treatment for ALI, involving exposure to a high concentration of oxygen. Unfortunately, hyperoxia induces the formation of reactive oxygen species which can cause an increase in 4-HNE (4-hydroxy 2 nonenal), a toxic byproduct of lipid peroxidation. Mitochondrial aldehyde dehydrogenase 2 (ALDH2) serves as an endogenous shield against oxidative stress-mediated damage by clearing 4-HNE. Alda-1 [(N-(1, 3 benzodioxol-5-ylmethyl)-2, 6- dichloro-benzamide)], a small molecular activator of ALDH2, protects against reactive oxygen species-mediated oxidative stress by promoting ALDH2 activity. As a result, Alda-1 shields against ischemic reperfusion injury, heart failure, stroke, and myocardial infarction. However, the mechanisms of Alda-1 in hyperoxia-induced ALI remains unclear. C57BL/6 mice implanted with Alzet pumps received Alda-1 in a sustained fashion while being exposed to hyperoxia for 48 h. The mice displayed suppressed immune cell infiltration, decreased protein leakage and alveolar permeability compared to controls. Mechanistic analysis shows that mice pretreated with Alda-1 also experience decreased oxidative stress and enhanced levels of p-Akt and mTOR pathway associated proteins. These results show that continuous delivery of Alda-1 protects against hyperoxia-induced lung injury in mice.

scholarly journals Association of Toll-Like Receptor Signaling and Reactive Oxygen Species: A Potential Therapeutic Target for Posttrauma Acute Lung Injury

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Meng Xiang ◽  
Janet Fan ◽  
Jie Fan
Keyword(s):  
Reactive Oxygen Species ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Response ◽  
Therapeutic Target ◽  
Major Trauma ◽  
Pulmonary Inflammation ◽  
Reactive Oxygen ◽  
Oxygen Species

Acute lung injury (ALI) frequently occurs in traumatic patients and serves as an important component of systemic inflammatory response syndrome (SIRS). Hemorrhagic shock (HS) that results from major trauma promotes the development of SIRS and ALI by priming the innate immune system for an exaggerated inflammatory response. Recent studies have reported that the mechanism underlying the priming of pulmonary inflammation involves the complicated cross-talk between Toll-like receptors (TLRs) and interactions between neutrophils (PMNs) and alveolar macrophages (AMϕ) as well as endothelial cells (ECs), in which reactive oxygen species (ROS) are the key mediator. This paper summarizes some novel mechanisms underlying HS-primed lung inflammation focusing on the role of TLRs and ROS, and therefore suggests a new therapeutic target for posttrauma ALI.

scholarly journals Anti-Inflammatory and Reactive Oxygen Species Suppression through Aspirin Pretreatment to Treat Hyperoxia-Induced Acute Lung Injury in NF-κB–Luciferase Inducible Transgenic Mice

Antioxidants ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 429 ◽  
Author(s):  
Chuan-Mu Chen ◽  
Yu-Tang Tung ◽  
Chi-Hsuan Wei ◽  
Po-Ying Lee ◽  
Wei Chen
Keyword(s):  
Reactive Oxygen Species ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Transgenic Mice ◽  
In Vivo Imaging ◽  
Reactive Oxygen ◽  
Luciferase Expression ◽  
Oxygen Species ◽  
Anti Inflammatory

Acute lung injury (ALI), a common cause of morbidity and mortality in intensive care units, results from either direct intra-alveolar injury or indirect injury following systemic inflammation and oxidative stress. Adequate tissue oxygenation often requires additional supplemental oxygen. However, hyperoxia causes lung injury and pathological changes. Notably, preclinical data suggest that aspirin modulates numerous platelet-mediated processes involved in ALI development and resolution. Our previous study suggested that prehospital aspirin use reduced the risk of ALI in critically ill patients. This research uses an in vivo imaging system (IVIS) to investigate the mechanisms of aspirin’s anti-inflammatory and antioxidant effects on hyperoxia-induced ALI in nuclear factor κB (NF-κB)–luciferase transgenic mice. To define mechanisms through which NF-κB causes disease, we developed transgenic mice that express luciferase under the control of NF-κB, enabling real-time in vivo imaging of NF-κB activity in intact animals. An NF-κB-dependent bioluminescent signal was used in transgenic mice carrying the luciferase genes to monitor the anti-inflammatory effects of aspirin. These results demonstrated that pretreatment with aspirin reduced luciferase expression, indicating that aspirin reduces NF-κB activation. In addition, aspirin reduced reactive oxygen species expression, the number of macrophages, neutrophil infiltration and lung edema compared with treatment with only hyperoxia treatment. In addition, we demonstrated that pretreatment with aspirin significantly reduced the protein levels of phosphorylated protein kinase B, NF-κB and tumor necrosis factor α in NF-κB–luciferase+/+ transgenic mice. Thus, the effects of aspirin on the anti-inflammatory response and reactive oxygen species suppressive are hypothesized to occur through the NF-κB signaling pathway. This study demonstrated that aspirin exerts a protective effect for hyperoxia-induced lung injury and thus is currently the drug conventionally used for hyperoxia-induced lung injury.

Identification of a Two-Step Mechanism Responsible for Antibody-Mediated Transfusion Related Acute Lung Injury (TRALI)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 846-846
Author(s):  
Christopher G.J. McKenzie ◽  
Michael Kim ◽  
Tarandeep Singh ◽  
John W. Semple
Keyword(s):  
Reactive Oxygen Species ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Mhc Class I ◽  
Reactive Oxygen ◽  
Lung Damage ◽  
Class I ◽  
Oxygen Species ◽  
Neutrophil Accumulation

Abstract Abstract 846 Transfusion-related acute lung injury (TRALI) is one of the leading causes of transfusion fatalities, and most TRALI reactions are thought to be caused by donor antibodies. It is currently thought that the donor antibodies activate pulmonary neutrophils to produce reactive oxygen species that damage lung tissue. There have been several animal models of TRALI developed including, for example, ex vivo lung models demonstrating the importance of human anti-neutrophil antibodies in TRALI, and in vivo models showing how biological response modifiers can induce recipient lung damage. An in vivo murine model of antibody-mediated TRALI was developed in 2006, and has also shown several similarities with human TRALI induction (Looney MR et al., J Clin Invest 116: 1615, 2006). Specifically, a monoclonal anti-mouse MHC class I antibody (34-1-2s) causes significant increases in excess lung water, lung vascular permeability and mortality within 2 hours after administration. These adverse reactions were found to be due to the antibody's ability to activate pulmonary neutrophils to produce reactive oxygen species (ROS) in an Fc receptor (FcR)-dependent manner. In contrast, however, it was recently shown that 34-1-2s induces pulmonary damage by activating macrophages to generate ROS in a complement (C5a)-dependent process (Strait RT J et al., Exp Med 208: 2525, 2011). In order to better understand this apparent controversy, we attempted to determine the nature of how 34-1-2s mediates its lung damaging properties. 34-1-2s was digested with pepsin or papain to produce F(ab')2 or Fc fragments respectively, and the fragments were tested for their ability to mediate TRALI reactions. In control mice, when intact 34-1-2s antibody was intravenously injected into either CB.17 mice with severe combined immunodeficiency or C5 deficient DBA/2 mice, increased shock, serum MIP-2 (murine equivalent to human IL-8) levels, pulmonary neutrophil accumulation, pulmonary edema and mortality all occurred within 2 hours. In contrast, however, injection with 34-1-2s F(ab')2 fragments was only able to generate MIP-2 production and pulmonary neutrophil accumulation; no lung damage or mortality occurred. Injection of 34-1-2s Fc fragments either alone or together with equal molar concentrations of F(ab')2 fragments failed to induce any lung damage or mortality. These results suggest that 34-1-2s recognition of it's cognate MHC class I antigen may be a priming reaction that stimulates MIP-2 and chemotaxis of neutrophils to the lungs, whereas the Fc portion of the intact molecule is responsible for the second step of exacerbating TRALI symptoms in a complement independent manner. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Peroxiredoxin 3 Inhibits Acetaminophen-Induced Liver Pyroptosis Through the Regulation of Mitochondrial ROS

2021 ◽  
Vol 12 ◽  
Author(s):  
Yue Wang ◽  
Yan Zhao ◽  
Zhecheng Wang ◽  
Ruimin Sun ◽  
Boyang Zou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cell Death ◽  
Liver Disease ◽  
Liver Injury ◽  
Oxygen Species ◽  
Mitochondrial Oxidative Stress ◽  
Mitochondrial Ros ◽  
Peroxiredoxin 3

Pyroptosis is a newly discovered form of cell death. Peroxiredoxin 3 (PRX3) plays a crucial role in scavenging reactive oxygen species (ROS), but its hepatoprotective capacity in acetaminophen (APAP)-induced liver disease remains unclear. The aim of this study was to assess the role of PRX3 in the regulation of pyroptosis during APAP-mediated hepatotoxicity. We demonstrated that pyroptosis occurs in APAP-induced liver injury accompanied by intense oxidative stress and inflammation, and liver specific PRX3 silencing aggravated the initiation of pyroptosis and liver injury after APAP intervention. Notably, excessive mitochondrial ROS (mtROS) was observed to trigger pyroptosis by activating the NLRP3 inflammasome, which was ameliorated by Mito-TEMPO treatment, indicating that the anti-pyroptotic role of PRX3 relies on its powerful ability to regulate mtROS. Overall, PRX3 regulates NLRP3-dependent pyroptosis in APAP-induced liver injury by targeting mitochondrial oxidative stress.

scholarly journals Hydrogen-rich saline ameliorated LPS-induced acute lung injury via autophagy inhibition through the ROS/AMPK/mTOR pathway in mice

2019 ◽  
Vol 244 (9) ◽  
pp. 721-727 ◽  
Author(s):  
Yong Wang ◽  
Jinghua Zhang ◽  
Jinsong Bo ◽  
Xuefen Wang ◽  
Jingnan Zhu
Keyword(s):  
Reactive Oxygen Species ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Reactive Oxygen ◽  
Lavage Fluid ◽  
Mtor Pathway ◽  
Oxygen Species ◽  
Malondialdehyde Content ◽  
Prevention And Treatment

Over-activation of autophagy due to increased levels of reactive oxygen species is a key mechanism of lipopolysaccharide-induced acute lung injury. Hydrogen-rich saline, an antioxidant, has been proved to be an effective agent for the prevention of acute lung injury, but the underlying mechanism remains unclear. Here, we investigated the mechanism through which hydrogen-rich saline prevents acute lung injury by focusing on autophagy regulation. The acute lung injury model was induced using lipopolysaccharide both in vivo and in vitro. The activation of autophagy was observed by detecting the expression of autophagy-related proteins using Western blotting. Lung histopathological changes, malondialdehyde content, wet/dry ratio, inflammatory cell count, protein content in bronchoalveolar lavage fluid, and cell viability were measured to evaluate the severity of acute lung injury. Intracellular reactive oxygen species levels were detected using dihydroethidium, which is a reactive oxygen species fluorescent probe. The results showed that the expression of Beclin-1 and microtubule-associated protein 1 light chain 3 II/I (LC3II/I ratio) was obviously increased after lipopolysaccharide administration. Pretreatment with hydrogen-rich saline markedly inhibited the expression of Beclin-1 and the LC3II/I ratio; ameliorated lung histopathological changes, malondialdehyde content and wet/dry ratio; and reduced protein content and infiltration of inflammatory cells in bronchoalveolar lavage fluid. These protective effects were also observed by pretreatment with autophagy inhibitor 3-methyladenine. Similar results were found in vitro. The production of reactive oxygen species and the activation of the AMPK/mTOR pathway were notably enhanced in MLE-12 cells after lipopolysaccharide treatment, and ameliorated by the hydrogen-rich medium. The activation of AMPK induced by lipopolysaccharide was also inhibited by pretreatment with N-acetyl-L-cysteine (a reactive oxygen species scavenger). In addition, the over-activation of autophagy was also suppressed by compound C (an AMPK inhibitor). In conclusion, hydrogen-rich saline alleviated lipopolysaccharide-induced acute lung injury by inhibiting excessive autophagy activation via the ROS/AMPK/mTOR pathway in mice. Hydrogen-rich saline may be a new therapeutic strategy for acute lung injury prevention and treatment in the future. Impact statement Acute lung injury (ALI), a common complication of many serious health issues, such as serious infection, burns, and shock, is one of the most common critical illnesses in clinical practice with a high mortality rate of 30–40%. There are still short of effective prevention and treatment measures. Evidence is growing that hydrogen-rich saline (HRS) may be an effective drug for the prevention and treatment of ALI. However, the mechanisms involved in have not been clearly understood. In this study, we investigated the underling mechanisms by focusing on autophagy regulation. The results showed that HRS ameliorated lipopolysaccharide-induced ALI in mice by inhibiting autophagy over-activation through ROS/AMPK/mTOR pathway. HRS may be a new therapeutic strategy for ALI prevention and treatment in the future.

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