Pretreatment with Coenzyme Q10 Combined with Aescin Protects against Sepsis-Induced Acute Lung Injury

2021 ◽  
pp. 1-23
Author(s):  
Fares E.M. Ali ◽  
Salwa F. Ahmed ◽  
Amira H. Eltrawy ◽  
Reda S. Yousef ◽  
Howaida S. Ali ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Combination Therapy ◽  
Lung Injury ◽  
Coenzyme Q10 ◽  
High Mobility ◽  
Male Rats ◽  
Reactive Protein ◽  
Mitogen Activated Protein ◽  
Combined Pretreatment ◽  
Anti Inflammatory

Sepsis-associated acute lung injury (ALI) is a critical condition characterized by severe inflammatory response and mitochondrial dysfunction. Coenzyme Q10 (CoQ10) and aescin (AES) are well-known for their anti-inflammatory activities. However, their effects on lipopolysaccharide (LPS)-induced lung injury have not been explored yet. Here, we asked whether combined pretreatment with CoQ10 and AES synergistically prevents LPS-induced lung injury. Fifty male rats were randomized into 5 groups: (1) control; (2) LPS-treated, rats received a single i.p. injection of LPS (8 mg/kg); (3) CoQ10-pretreated, (4) AES-pretreated, or (5) combined-pretreated; animals received CoQ10 (100 mg/kg), AES (5 mg/kg), or both orally for 7 days before LPS injection. Combined CoQ10 and AES pretreatment significantly reduced lung injury markers; 52.42% reduction in serum C-reactive protein (CRP), 53.69% in alkaline phosphatase (ALKP) and 60.26% in lactate dehydrogenase (LDH) activities versus 44.58, 37.38, and 48.6% in CoQ10 and 33.81, 34.43, and 39.29% in AES-pretreated groups, respectively. Meanwhile, combination therapy significantly reduced interleukin (IL)-1β and tumor necrosis factor (TNF)-α expressions compared to monotherapy (<i>p</i> &#x3c; 0.05). Additionally, combination therapy prevented LPS-induced histological and mitochondrial abnormalities greater than separate drugs. Western blotting indicated that combination therapy significantly suppressed nucleotide-binding oligomerization domain (NOD)-like receptors-3 (NLRP-3) inflammasome compared to separate drugs (<i>p</i> &#x3c; 0.05). Further, combination therapy significantly decreased the expression of signaling cascades, p38 mitogen-activated protein kinases (p38 MAPK), nuclear factor kappa B (NF-κB)-p65, and extracellular-regulated kinases 1/2 (ERK1/2) versus monotherapy (<i>p</i> &#x3c; 0.05). Interestingly, combined pretreatment significantly downregulated high mobility group box-1 (HMGB1) by 72.93%, and toll-like receptor 4 (TLR4) by −0.93-fold versus 61.92%, −0.83-fold in CoQ10 and 38.67%, −0.70-fold in AES pretreatment, respectively. Our results showed for the first time that the enhanced anti-inflammatory effect of combined CoQ10 and AES pretreatment prevented LPS-induced ALI via suppression of NLRP-3 inflammasome through regulation of HMGB1/TLR4 signaling pathway and mitochondrial stabilization.

scholarly journals Corylin Ameliorates LPS-Induced Acute Lung Injury via Suppressing the MAPKs and IL-6/STAT3 Signaling Pathways

2021 ◽  
Vol 14 (10) ◽  
pp. 1046
Author(s):  
I-Chen Chen ◽  
Shu-Chi Wang ◽  
Yi-Ting Chen ◽  
Hsin-Han Tseng ◽  
Po-Len Liu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Immune Cell ◽  
Therapeutic Potential ◽  
Lavage Fluid ◽  
Mitogen Activated Protein ◽  
Associated Proteins ◽  
Anti Inflammatory

Acute lung injury (ALI) is a high mortality disease with acute inflammation. Corylin is a compound isolated from the whole plant of Psoralea corylifolia L. and has been reported to have anti-inflammatory activities. Herein, we investigated the therapeutic potential of corylin on lipopolysaccharides (LPS)-induced ALI, both in vitro and in vivo. The levels of proinflammatory cytokine secretions were analyzed by ELISA; the expressions of inflammation-associated proteins were detected using Western blot; and the number of immune cell infiltrations in the bronchial alveolar lavage fluid (BALF) were detected by multicolor flow cytometry and lung tissues by hematoxylin and eosin (HE) staining, respectively. Experimental results indicated that corylin attenuated LPS-induced IL-6 production in human bronchial epithelial cells (HBEC3-KT cells). In intratracheal LPS-induced ALI mice, corylin attenuated tissue damage, suppressed inflammatory cell infiltration, and decreased IL-6 and TNF-α secretions in the BALF and serum. Moreover, it further inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs), including p-JNK, p-ERK, p-p38, and repressed the activation of signal transducer and activator of transcription 3 (STAT3) in lungs. Collectively, our results are the first to demonstrate the anti-inflammatory effects of corylin on LPS-induced ALI and suggest corylin has significant potential as a novel therapeutic agent for ALI.

Asatone Prevents Acute Lung Injury by Reducing Expressions of NF-κB, MAPK and Inflammatory Cytokines

2018 ◽  
Vol 46 (03) ◽  
pp. 651-671 ◽  
Author(s):  
Heng-Yuan Chang ◽  
Yi-Chuan Chen ◽  
Jaung-Geng Lin ◽  
I-Hsin Lin ◽  
Hui-Fen Huang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Bronchoalveolar Lavage Fluid ◽  
Lavage Fluid ◽  
Oxidative Enzymes ◽  
Mitogen Activated Protein Kinases ◽  
Cell Counts ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory

Asatone is an active component extracted from the Chinese herb Radix et Rhizoma Asari. Our preliminary studies have indicated that asatone has an anti-inflammatory effect on RAW 264.7 culture cells challenged with lipopolysaccharide (LPS). Acute lung injury (ALI) has high morbidity and mortality rates due to the onset of serious lung inflammation and edema. Whether asatone prevents ALI LPS-induced requires further investigation. In vitro studies revealed that asatone at concentrations of 2.5–20[Formula: see text][Formula: see text]g/mL drastically prevented cytotoxicity and concentration-dependently reduced NO production in the LPS-challenged macrophages. In an in vivo study, the intratracheal administration of LPS increased the lung wet/dry ratio, myeloperoxidase activity, total cell counts, white blood cell counts, NO, iNOS, COX, TNF-[Formula: see text], IL-1[Formula: see text], and IL-6 in the bronchoalveolar lavage fluid as well as mitogen-activated protein kinases in the lung tissues. Pretreatment with asatone could reverse all of these effects. Asatone markedly reduced the levels of TNF-[Formula: see text] and IL-6 in the lung and liver, but not in the kidney of mice. By contrast, LPS reduced anti-oxidative enzymes and inhibited NF-[Formula: see text]B activations, whereas asatone increased anti-oxidative enzymes in the bronchoalveolar lavage fluid and NF-[Formula: see text]B activations in the lung tissues. Conclusively, asatone can prevent ALI through various anti-inflammatory modalities, including the major anti-inflammatory pathways of NF-[Formula: see text]B and mitogen-activated protein kinases. These findings suggest that asatone can be applied in the treatment of ALI.

scholarly journals High-Mobility Group Box 1 (HMGB1) and Autophagy in Acute Lung Injury (ALI): A Review

2019 ◽  
Vol 25 ◽  
pp. 1828-1837 ◽  
Author(s):  
Lihua Qu ◽  
Chao Chen ◽  
YangYe Chen ◽  
Yi Li ◽  
Fang Tang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
High Mobility ◽  
High Mobility Group

scholarly journals In vitro and in vivo assessment of the protective effect of sufentanil in acute lung injury

2021 ◽  
Vol 49 (2) ◽  
pp. 030006052098635
Author(s):  
Qi Gao ◽  
Ningqing Chang ◽  
Donglian Liu
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Protective Effect ◽  
High Mobility ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Inflammatory Factors ◽  
Luciferase Reporter ◽  
Hmgb1 Protein

Objectives To investigate the mechanisms underlying the protective effect of sufentanil against acute lung injury (ALI). Material and Methods Rats were administered lipopolysaccharide (LPS) by endotracheal instillation to establish a model of ALI. LPS was used to stimulate BEAS-2B cells. The targets and promoter activities of IκB were assessed using a luciferase reporter assay. Apoptosis of BEAS-2B cells was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling. Results Sufentanil treatment markedly reduced pathological changes in lung tissue, pulmonary edema and secretion of inflammatory factors associated with ALI in vivo and in vitro. In addition, sufentanil suppressed apoptosis induced by LPS and activated NF-κB both in vivo and in vitro. Furthermore, upregulation of high mobility group box protein 1 (HMGB1) protein levels and downregulation of miR-129-5p levels were observed in vivo and in vitro following sufentanil treatment. miR-129-5p targeted the 3ʹ untranslated region and its inhibition decreased promoter activities of IκB-α. miR-129-5p inhibition significantly weakened the protective effect of sufentanil on LPS-treated BEAS-2B cells. Conclusion Sufentanil regulated the miR-129-5p/HMGB1 axis to enhance IκB-α expression, suggesting that sufentanil represents a candidate drug for ALI protection and providing avenues for clinical treatment.

scholarly journals Management of Acute Lung Injury: Palmitoylethanolamide as a New Approach

2021 ◽  
Vol 22 (11) ◽  
pp. 5533
Author(s):  
Alessio Filippo Peritore ◽  
Ramona D’Amico ◽  
Rosalba Siracusa ◽  
Marika Cordaro ◽  
Roberta Fusco ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
B Cells ◽  
Lung Injury ◽  
Weight Ratio ◽  
Dry Weight ◽  
Mitogen Activated Protein Kinase ◽  
Histopathological Analysis ◽  
Nuclear Factor ◽  
Intratracheal Administration ◽  
Mitogen Activated Protein

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common and devastating clinical disorders with high mortality and no specific therapy. Lipopolysaccharide (LPS) is usually used intratracheally to induce ALI in mice. The aim of this study was to examine the effects of an ultramicronized preparation of palmitoylethanolamide (um-PEA) in mice subjected to LPS-induced ALI. Histopathological analysis reveals that um-PEA reduced alteration in lung after LPS intratracheal administration. Besides, um-PEA decreased wet/dry weight ratio and myeloperoxidase, a marker of neutrophils infiltration, macrophages and total immune cells number and mast cells degranulation in lung. Moreover, um-PEA could also decrease cytokines release of interleukin (IL)-6, interleukin (IL)-1β, tumor necrosis factor (TNF)-α and interleukin (IL)-18. Furthermore, um-PEA significantly inhibited the phosphorylation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation in ALI, and at the same time decreased extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38/MAPK) expression, that was increased after LPS administration. Our study suggested that um-PEA contrasted LPS-induced ALI, exerting its potential role as an adjuvant anti-inflammatory therapeutic for treating lung injury, maybe also by p38/NF-κB pathway.

Class B Scavenger Receptors BI and BII Protect Against LPS-induced Acute Lung Injury in Mice by Mediating LPS Clearance

2021 ◽  
Author(s):  
Irina N. Baranova ◽  
Alexander V. Bocharov ◽  
Tatyana G. Vishnyakova ◽  
Zhigang Chen ◽  
Anna A. Birukova ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Transgenic Mice ◽  
Neutrophil Infiltration ◽  
Lavage Fluid ◽  
Protective Role ◽  
Lung Damage ◽  
Wild Type ◽  
Class B ◽  
Anti Inflammatory

Recent studies suggest an anti-inflammatory protective role for class B scavenger receptor BI (SR-BI) in endotoxin-induced inflammation and sepsis. Other data, including ours, provide evidence for an alternative role of SR-BI, facilitating bacterial and endotoxin uptake, and contributing to inflammation and bacterial infection. Enhanced endotoxin susceptibility of SR-BI deficient mice due to their anti-inflammatory glucocorticoid deficiency complicates understanding SR-BI’s role in endotoxemia/sepsis, calling for use of alternative models. In this study, using hSR-BI and hSR-BII transgenic mice, we found that SR-BI and to a lesser extent its splicing variant SR-BII, protects against LPS-induced lung damage. At 20 hours after intratracheal LPS instillation the extent of pulmonary inflammation and vascular leakage was significantly lower in hSR-BI and hSR-BII transgenic mice compared to wild type mice. Higher bronchoalveolar lavage fluid (BALF) inflammatory cell count and protein content as well as lung tissue neutrophil infiltration found in wild type mice was associated with markedly (2-3 times) increased pro-inflammatory cytokine production as compared to transgenic mice following LPS administration. Markedly lower endotoxin levels detected in BALF of transgenic vs. wild type mice along with the significantly increased BODIPY-LPS uptake observed in lungs of hSR-BI and hSR-BII mice 20 hours after the IT LPS injection suggest that hSR-BI and hSR-BII-mediated enhanced LPS clearance in the airways could represent the mechanism of their protective role against LPS-induced acute lung injury.

Bilobalide, a bioactive compound on sepsis-induced acute lung injury through its anti-inflammatory and antioxidative activity

2021 ◽  
Vol 17 (73) ◽  
pp. 163
Author(s):  
Yi Zhu ◽  
Feng Wang ◽  
Jian Huang ◽  
Jun Li ◽  
Kang Chen ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Antioxidative Activity ◽  
Bioactive Compound ◽  
Anti Inflammatory

The Effect of Experimental Diabetes on High Mobility Group Box 1 Protein Expression in Endotoxin-Induced Acute Lung Injury

2011 ◽  
Vol 168 (1) ◽  
pp. 111-118 ◽  
Author(s):  
Satoshi Hagiwara ◽  
Hideo Iwasaka ◽  
Chihiro Shingu ◽  
Shigekiyo Matumoto ◽  
Akira Hasegawa ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Protein Expression ◽  
Experimental Diabetes ◽  
High Mobility ◽  
High Mobility Group
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