Astragaloside IV pre-treatment attenuates PM2.5-induced lung injury in rats: Impact on autophagy, apoptosis and inflammation

Lung tissues are frequently exposed to a hyperoxia environment, which leads to oxidative stress injuries. Hydrogen sulfide (H2S) is widely implicated in physiological and pathological processes and its antioxidant effect has attracted much attention. Therefore, in this study, we used hydrogen peroxide (H2O2) as an oxidative damage model to investigate the protective mechanism of H2S in lung injury. Cell death induced by H2O2 treatment could be significantly attenuated by the pre-treatment of H2S, resulting in a decrease in the Bax/Bcl-2 ratio and the inhibition of caspase-3 activity in human lung epithelial cell line A549 cells. Additionally, the results showed that H2S decreased reactive oxygen species (ROS), as well as neutralized the damaging effects of H2O2 in mitochondria energy-producing and cell metabolism. Pre-treatment of H2S also decreased H2O2-induced suppression of endogenous H2S production enzymes, cystathionine-beta-synthase (CBS), cystathionine-gamma-lyase (CSE), and 3-mercapto-pyruvate sulfurtransferase (MPST). Furthermore, the administration of H2S attenuated [Ca2+] overload and endoplasmic reticulum (ER) stress through the mitogen-activated protein kinase (MAPK) signaling pathway. Therefore, H2S might be a potential therapeutic agent for reducing ROS and ER stress-associated apoptosis against H2O2-induced lung injury.

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Amifostine Pre-Treatment Attenuates Lung Injury, but Not Inflammation, in Rats Intracheally Instilled with Particulate Matter Rich in Transition Metals.

10.1164/ajrccm-conference.2009.179.1_meetingabstracts.a3166 ◽

2009 ◽

Author(s):

AK Farraj ◽

DW Winsett ◽

N Haykal-Coates ◽

MS Hazari ◽

AP Carll ◽

...

Keyword(s):

Particulate Matter ◽

Transition Metals ◽

Lung Injury ◽

Pre Treatment

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Effect of Hypertonic Saline Pre-treatment on Ischemia–Reperfusion Lung Injury in Pig

The Journal of Heart and Lung Transplantation ◽

10.1016/j.healun.2008.07.004 ◽

2008 ◽

Vol 27 (9) ◽

pp. 1023-1030 ◽

Cited By ~ 12

Author(s):

Antoine Roch ◽

Matthias Castanier ◽

Vincent Mardelle ◽

Delphine Trousse ◽

Valérie Marin ◽

...

Keyword(s):

Lung Injury ◽

Hypertonic Saline ◽

Ischemia Reperfusion ◽

Pre Treatment

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Pre-Treatment with Allopurinol or Uricase Attenuates Barrier Dysfunction but Not Inflammation during Murine Ventilator-Induced Lung Injury

PLoS ONE ◽

10.1371/journal.pone.0050559 ◽

2012 ◽

Vol 7 (11) ◽

pp. e50559 ◽

Cited By ~ 15

Author(s):

Maria T. Kuipers ◽

Hamid Aslami ◽

Alexander P. J. Vlaar ◽

Nicole P. Juffermans ◽

Anita M. Tuip-de Boer ◽

...

Keyword(s):

Lung Injury ◽

Barrier Dysfunction ◽

Ventilator Induced Lung Injury ◽

Pre Treatment

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Ninjinyoeito Ameliorated Cigarette Smoke Extract-induced Apoptosis and Inflammation Through JNK Signaling Inhibition in Human Lung Fibroblasts

10.21203/rs.3.rs-941651/v1 ◽

2021 ◽

Author(s):

Kenta Murata ◽

Nina Fujita ◽

Ryuji Takahashi

Keyword(s):

Lung Injury ◽

Cigarette Smoke ◽

Human Lung ◽

Cigarette Smoke Extract ◽

Lung Fibroblasts ◽

Ros Production ◽

Jnk Signaling ◽

Human Lung Fibroblasts ◽

Induced Apoptosis ◽

Apoptosis And Inflammation

Abstract BackgroundCigarette smoke is a major risk factor for various lung diseases, such as chronic obstructive pulmonary disease (COPD). Ninjinyoeito (NYT), a traditional Chinese medicine, has been prescribed for patients with post-illness or post-operative weakness, fatigue, loss of appetite, rash, cold limbs, and anemia. In addition to its traditional use, NYT has been prescribed for treating frailty in gastrointestinal, respiratory, and urinary functions. Further, NYT treatment can ameliorate cigarette smoke-induced lung injury, which is a destructive index in mice; however, the detailed underlying mechanism remains unknown. PurposeThe purpose of this study was to investigate whether NYT ameliorates cigarette smoke-induced lung injury and inflammation in human lung fibroblasts and determine its mechanism of action. MethodsWe prepared a cigarette smoke extract (CSE) from commercially available cigarettes to induce cell injury and inflammation in the human lung fibroblast cell line HFL1. The cells were pretreated with NYT for 24 h prior to CSE exposure. Cytotoxicity and cell viability were measured by lactate dehydrogenase (LDH) cytotoxicity assay and cell counting kit (CCK)-8. IL-8 level in the cell culture medium was measured by performing Enzyme-Linked Immuno Sorbent Assay (ELISA). To clarify the mechanisms of NYT, we used CellROX Green Reagent for reactive oxygen species (ROS) production and western blotting analysis for cell signaling.ResultsExposure of HFL1 cells to CSE for 24 h induced apoptosis and interleukin (IL)-8 release. Pretreatment with NYT inhibited apoptosis and IL-8 release. Furthermore, CSE exposure for 24 h increased the production of ROS and phosphorylation levels of p38 and JNK. Pretreatment with NYT only inhibited CSE-induced JNK phosphorylation, and not ROS production and p38 phosphorylation. These results suggest that NYT acts as a JNK-specific inhibitor.ConclusionNYT treatment ameliorated CSE-induced apoptosis and inflammation by inhibiting the JNK signaling pathway. Finally, these results suggest that NYT may be a promising therapeutic agent for patients with COPD.

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Gadolinium Chloride Attenuates Sepsis-Induced Pulmonary Apoptosis and Acute Lung Injury

ISRN Inflammation ◽

10.5402/2012/393481 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Osama A. Kishta ◽

Peter Goldberg ◽

Sabah N. A. Husain

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Water Content ◽

Interleukin 1 ◽

Gadolinium Chloride ◽

Myeloperoxidase Activity ◽

Mrna Levels ◽

Lung Water ◽

Pre Treatment ◽

Lung Water Content

Gadolinium chloride (GdCl3), a Kupffer cells inhibitor, attenuates acute lung injury; however, the mechanisms behind this effect are not completely elucidated. We tested the hypothesis that GdCl3 acts through the inhibition of lung parenchymal cellular apoptosis. Two groups of rats were injected intraperitoneally with saline or E. coli lipopolysaccharide. In two additional groups, rats were injected with GdCl3 24 hrs prior to saline or LPS administration. At 12 hrs, lung injury, inflammation, and apoptosis were studied. Lung water content, myeloperoxidase activity, pulmonary apoptosis and mRNA levels of interleukin-1β, -2, -5, -6, -10 and TNF-α rose significantly in LPS-injected animals. Pretreatment with GdCl3 significantly reduced LPS-induced elevation of pulmonary water content, myeloperoxidase activity, cleaved caspase-3 intensity, and attenuated pulmonary TUNEL-positive cells. GdCl3 pre-treatment upregulated IL-1β, -2 and -10 pulmonary gene expression without significantly affecting the others. These results suggest that GdCl3 attenuates acute lung injury through its effects on pulmonary parenchymal apoptosis.

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A Peptide Inhibitor of NADPH Oxidase (NOX2) Activation Markedly Decreases Mouse Lung Injury and Mortality Following Administration of Lipopolysaccharide (LPS)

International Journal of Molecular Sciences ◽

10.3390/ijms20102395 ◽

2019 ◽

Vol 20 (10) ◽

pp. 2395 ◽

Cited By ~ 3

Author(s):

Aron B. Fisher ◽

Chandra Dodia ◽

Shampa Chatterjee ◽

Sheldon I. Feinstein

Keyword(s):

Lung Injury ◽

Nadph Oxidase ◽

Phospholipase A2 ◽

Protein A ◽

Surfactant Protein ◽

Peptide Inhibitor ◽

Mouse Lung ◽

Amplex Red ◽

Pre Treatment ◽

Phospholipase A2 Activity

We have previously derived three related peptides, based on a nine-amino acid sequence in human or rat/mouse surfactant protein A, that inhibit the phospholipase A2 activity of peroxiredoxin 6 (Prdx6) and prevent the activation of lung NADPH oxidase (type 2). The present study evaluated the effect of these Prdx6-inhibitory peptides (PIP) in a mouse (C57Bl/6) model of acute lung injury following lipopolysaccharide (LPS) administration. All three peptides (PIP-1, 2 and 3) similarly inhibited the production of reactive O2 species (ROS) in isolated mouse lungs as detected by the oxidation of Amplex red. PIP-2 inhibited both the increased phospholipase A2 activity of Prdx6 and lung reactive oxygen species (ROS) production following treatment of mice with intratracheal LPS (5 µg/g body wt.). Pre-treatment of mice with PIP-2 prevented LPS-mediated lung injury while treatment with PIP-2 at 12 or 16 h after LPS administration led to reversal of lung injury when evaluated 12 or 8 h later, respectively. With a higher dose of LPS (15 µg/g body wt.), mortality was 100% at 48 h in untreated mice but only 28% in mice that were treated at 12–24 h intervals, with PIP-2 beginning at 12 h after LPS administration. Treatment with PIP-2 also markedly decreased mortality after intraperitoneal LPS (15 µg/g body wt.), used as a model of sepsis. This study shows the dramatic effectiveness of a peptide inhibitor of Prdx6 against lung injury and mouse mortality in LPS models. We propose that the PIP nonapeptides may be a useful modality to prevent or to treat human ALI.

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