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.

scholarly journals Shen-su-yin, a Traditional Herbal Medicine, Attenuates Lipopolysaccharide-induced Acute Lung Injury in Rats Through Its Anti-inflammatory and Anti-oxidative Effects

2021 ◽  
Author(s):  
Peng Xiao ◽  
Jun Ke ◽  
Jiuyun Zhang ◽  
Haijun Zhou ◽  
Wuhong Zheng
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Weight Ratio ◽  
Oxygenation Index ◽  
Dry Weight ◽  
Signalling Pathway ◽  
Lung Injury Score ◽  
High Dose ◽  
Histopathological Analysis ◽  
Anti Inflammatory

Abstract Most components of Shen-su-yin (SSY), an herbal formula, have anti-inflammatory and antioxidant activities. The present study was designed to investigate potential effects and mechanisms of SSY on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats. 48 rats were randomly divided into 4 groups: control (Ctrl) group, LPS-induced ALI group, low- (SSY-LD) and high- (SSY-HD) dose SSY-treated ALI group. SSY was administered to SSY-treated rats immediately after LPS induction. After 24 hours, blood gas analysis and lactate determination were performed; and bronchoalveolar lavage fluid was collected for detecting protein concentration and levels of cytokines. Lung tissues were obtained for Western blot analysis, histopathological analysis, wet-to-dry weight ratio calculation and measurement of oxidative stress levels. SSY improved oxygenation index and mean arterial pressure, decreased levels of lactate and heart rate, alleviated lung histopathology indexes including lung injury score, wet-to-dry weight ratio and exudation of protein as well as inflammatory cells in ALI rats. Furthermore, SSY reduced levels of pro-inflammatory and oxidative mediums, while increasing levels of anti-inflammatory cytokine and anti-oxidative activity in lung tissues. SSY also suppressed NF-κB signalling pathway and further activated Keap1-Nrf2-ARE signalling pathway activated by LPS. Moreover, all the effects caused by SSY in the SSY-HD group were more encouraging than those in the SSY-LD group. The results indicate that the preventive use of SSY can alleviate ALI through the anti-inflammatory and antioxidant effects mediated by inhibition of NF-κB signalling pathway and activation of Keap1-Nrf2-ARE signalling pathway, and the effect of high dose is better.

scholarly journals Echinacoside attenuates lipopolysaccharide-induced acute lung injury in newborn mice via inactivation of NF- κB/NLRP3 signaling pathway

2020 ◽  
Vol 19 (9) ◽  
pp. 1815-1819
Author(s):  
Meijiao Fu ◽  
Tong Shen ◽  
Ying Yang ◽  
Yaling Zheng ◽  
Lilin Zhong
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Lung Tissue ◽  
Tissue Injury ◽  
Weight Ratio ◽  
Dry Weight ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Newborn Mice ◽  
Pyrin Domain

Purpose: To investigate the effect of echinacoside (ECH) on acute lung injury (ALI) and the underlying mechanism of action.Methods: The ALI model was established through intranasal instillation of lipopolysaccharide (LPS). Lung tissue damage was determined using hematoxylin and eosin (H&E) staining and lung wet-to-dry–weight ratio. Bronchoalveolar lavage fluid (BALF) protein concentration, cell count, and cytokine level were evaluated. Western blotting was used to determine protein expression level.Results: ECH attenuated lung tissue injury and lung wet-to-dry–weight ratio in the ALI model (p < 0.01). The total protein content and number of total cells, neutrophils, and macrophages increased in BALF of mice treated with LPS, but these increases were reversed by ECH treatment (p < 0.01). The levels of TNF-α and IL-1β increased in BALF and lung tissue of LPS-treated mice; however, ECH treatment decreased these changes (p < 0.01). In addition, ECH inhibited the activation of the nuclear factor-κB (NF-κB)/NLR family pyrin domain containing 3 (NLRP3) pathway in LPS-treated mice (p < 0.01).Conclusion: Echinacoside attenuates LPS-induced ALI via inactivation of the NF-κB/NLRP3 pathway, making echinacoside a potential drug for the treatment of ALI. Keywords: Echinacoside, Acute lung injury, Lipopolysaccharide, Nuclear factor-κB, NLR family pyrin domain containing 3

scholarly journals Amelioration of Lipopolysaccharide-Induced Acute Lung Injury in Rats by Na-H Exchanger-1 Inhibitor Amiloride Is Associated with Reversal of ERK Mitogen-Activated Protein Kinase

2018 ◽  
Vol 2018 ◽  
pp. 1-7
Author(s):  
Yan Zhang ◽  
Hao He ◽  
Boran Zhang ◽  
Qinghong Chen ◽  
Shanglong Yao ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Protein Kinase ◽  
Lung Injury ◽  
Intravenous Injection ◽  
Lung Tissue ◽  
Normal Saline ◽  
Weight Ratio ◽  
Mitogen Activated Protein Kinase ◽  
Necrosis Factor Alpha ◽  
Mitogen Activated Protein

Background. Na-H exchanger-1 (NHE-1) is expressed in the lung of rats. Accumulating evidence shows that Na-H exchangers are involved in inflammation. Amiloride, an inhibitor of NHE-1, inhibits the activation of macrophages and endothelial cells and reduces their production of cytokines. Since these processes have been implicated in acute lung injury (ALI) induced by lipopolysaccharide (LPS), we examined the protective effect of amiloride on ALI induced by LPS in rats. Material and Methods. ALI in specific pathogen-free male Sprague-Dawley rats was induced by an intravenous injection of 6 mg/kg LPS. Amiloride pretreated rats received an intravenous injection of 10 mg/kg amiloride 30 min before the administration of LPS. Controls received normal saline in a similar manner. All animals were sacrificed 6 h after LPS or normal saline administration. The degree of ALI was assessed by wet-to-dry weight ratio (W/D) and lung histological examination. Neutrophilic infiltration was determined by myeloperoxidase (MPO) activity in lung tissue. Concentrations of total protein (TP), tumor necrosis factor-alpha (TNF-α), and macrophage inflammatory protein-2 (MIP-2) in bronchoalveolar lavage fluid (BALF) were also measured. Expression of NHE-1 and mitogen-activated protein kinase (MAPK) p38, p-p38, ERK, and p-ERK was evaluated by western blot analysis. Results. Pretreatment with amiloride significantly reduced the increase in W/D, ALI score, lung tissue MPO activity, concentrations of TP, TNF-α, and MIP-2 in BALF, resulting in attenuation of ALI induced by LPS. Meanwhile, levels of NHE-1 and p-ERK proteins were reversed, whereas that of p-p38 was not. Conclusions. These findings suggest that NHE-1 inhibitor amiloride could attenuate ALI induced by LPS in rats. This effect is mediated through reversal of ERK.

Inactivation of Nf-κb Pathway by Taxifolin Attenuates Sepsis-Induced Acute Lung Injury

2019 ◽  
Vol 18 (2) ◽  
pp. 176-182
Author(s):  
Chen Weiyan ◽  
Deng Wujian ◽  
Chen Songwei
Keyword(s):  
Acute Lung Injury ◽  
B Cells ◽  
Lung Injury ◽  
Signaling Pathway ◽  
Light Chain ◽  
Cecal Ligation ◽  
Nuclear Factor ◽  
Kappa Light Chain ◽  
Cecal Ligation And Puncture ◽  
Light Chain Enhancer

Acute lung injury is a clinical syndrome consisting of a wide range of acute hypoxemic respiratory failure disorders. Sepsis is a serious complication caused by an excessive immune response to pathogen-induced infections, which has become a major predisposing factor for acute lung injury. Taxifolin is a natural flavonoid that shows diverse therapeutic benefits in inflammation- and oxidative stress-related diseases. In this study, we investigated the role of taxifolin in a mouse model of cecal ligation and puncture-induced sepsis. Cecal ligation and puncture-operated mice presented damaged alveolar structures, thickened alveolar walls, edematous septa, and hemorrhage compared to sham-treated controls. Cecal ligation and puncture mice also showed increased wet-to-dry (W/D) lung weight ratio and elevated total protein concentration and lactate dehydrogenase level in bronchoalveolar lavage fluid. Taxifolin treatment protected animals against sepsis-induced pulmonary damage and edema. Septic mice presented compromised antioxidant capacity, whereas the administration of taxifolin prior to cecal ligation and puncture surgery decreased malondialdehyde concentration and enhanced the levels of reduced glutathione and superoxide dismutase in mice with sepsis-induced acute lung injury. Moreover, cecal ligation and puncture-operated mice showed markedly higher levels of proinflammatory cytokines relative to sham-operated group, while taxifolin treatment effectively mitigated sepsis-induced inflammation in mouse lungs. Further investigation revealed that taxifolin suppressed the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway in cecal ligation and puncture-challenged mice by regulating the phosphorylation of p65 and IκBα. In conclusion, our study showed that taxifolin alleviated sepsis-induced acute lung injury via the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway, suggesting the therapeutic potential of taxifolin in the treatment sepsis-induced acute lung injury.

Shen-Fu Attenuates Endotoxin-Induced Acute Lung Injury in Rats

2006 ◽  
Vol 34 (04) ◽  
pp. 613-621 ◽  
Author(s):  
Yanning Qian ◽  
Jie Sun ◽  
Zhongyun Wang ◽  
Jianjun Yang
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Pulmonary Inflammation ◽  
Weight Ratio ◽  
Dry Weight ◽  
Nf Kappa B ◽  
Lung Weight ◽  
Tnf Α ◽  
Male Wistar Rats

Sepsis is associated with the highest risk of progression to acute lung injury or acute respiratory distress syndrome. Shen-Fu has been advocated to treat many severely ill patients. Our study was designed to investigate the effect of Shen-Fu on endotoxin-induced acute lung injury in vivo. Adult male Wistar rats were randomly divided into 6 groups: controls; those challenged with endotoxin (5 mg/kg) and treated with saline; those challenged with endotoxin (5 mg/kg) and treated with Shen-Fu (1 mg/kg); those challenged with endotoxin (5 mg/kg) and treated with Shen-Fu (10 mg/kg); increase challenged with endotoxin (5 mg/kg) and treated with Shen-Fu (100 mg/kg); saline injected and treated with Shen-Fu (100 mg/kg). TNF-α, IL-6, and NF-kappa B were investigated in the lung two hours later. Myeloperoxidase (MPO) activity and wet/dry weight ratio were investigated six hours later. Intravenous administration of endotoxin provoked significant lung injury, which was characterized by increment increase of MPO activity and wet/dry lung weight ratio, and TNF-α and IL-6 expression and NF-kappa B activation. Shen-Fu (10,100 mg/kg) decreased MPO activity and wet/dry weight ratio and inhibited TNF-α and IL-6 production, endotoxin-induced NF-kappa B activation. Our results indicated that Shen-Fu at a dose of higher than 10 mg/kg inhibited endotoxin-induced pulmonary inflammation in vivo.

scholarly journals Ganoderic acid A attenuates lipopolysaccharide-induced lung injury in mice

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Bing Wan ◽  
Yan Li ◽  
Shuangshuang Sun ◽  
Yang Yang ◽  
Yanling LV ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Mouse Model ◽  
Weight Ratio ◽  
Dry Weight ◽  
Lavage Fluid ◽  
Myeloperoxidase Activity ◽  
Protective Effects ◽  
Ganoderic Acid ◽  
Lower Lung

Abstract The present study aimed to investigate the protective effects of ganoderic acid A (GAA) on lipopolysaccharide (LPS)-induced acute lung injury. In mouse model of LPS-induced acute lung injury, we found that GAA led to significantly lower lung wet-to-dry weight ratio and lung myeloperoxidase activity, and attenuated pathological damages. In addition, GAA increased superoxide dismutase activity, but decreased malondialdehyde content and proinflammatory cytokines levels in the bronchoalveolar lavage fluid. Mechanistically, GAA reduced the activation of Rho/ROCK/NF-κB pathway to inhibit LPS-induced inflammation. In conclusion, our study suggests that GAA attenuates acute lung injury in mouse model via the inhibition of Rho/ROCK/NF-κB pathway.

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