A New Approach to Sepsis Treatment by Rasagiline: A Molecular, Biochemical and Histopathological Study

Abstract Aim:We aimed to investigate the effects of rasagiline, which has a strong antioxidant, anti-apoptotic and anti-inflammatory effect, on acute lung injury that develops in the sepsis model induced with the CLP in rats. Main Methods:The rats were separated into the following six groups, Group 1: Sham, Group 2: Sham + Rasegiline 4 mg/kg, Group 3: Sepsis, Group 4: Sepsis + Rasegiline 1 mg/kg, Group 5: Sepsis + Rasegiline 2 mg/kg, Group 6: Sepsis + Rasegiline 4 mg/kg. A total of 4 holes were opened with a 16-gauge needle through the cecum distal to the point of ligation. Key Findings:GSH levels appear to improve due to increased doses of rasagiline, while SOD activity appears to improve only at the high dose of rasagiline. There was a statistically significant improvement in the doses of R2 and R4. This improvement in Tnf-α, IL1β, IL6, NF-κβand HMGB1 expression increased dose-dependent at R2 and R4 doses. In increased doses, rasagiline appears to prevent the development of edema, the formation of inflammation, and hemorrhagic areas are almost similar to healthy tissue. Significance: Rasagiline exerts both antioxidant and anti-inflammatory effects on CLP induced acute lung injury in rats.

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Propofol Activation of the Nrf2 Pathway Is Associated with Amelioration of Acute Lung Injury in a Rat Liver Transplantation Model

Oxidative Medicine and Cellular Longevity ◽

10.1155/2014/258567 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 34

Author(s):

Weifeng Yao ◽

Gangjian Luo ◽

Guosong Zhu ◽

Xinjin Chi ◽

Ailan Zhang ◽

...

Keyword(s):

Liver Transplantation ◽

Acute Lung Injury ◽

Lung Injury ◽

Water Content ◽

High Dose ◽

Lung Pathology ◽

Lung Water ◽

Sod Activity ◽

Nrf2 Pathway ◽

Lung Water Content

Objective. This study aimed to investigate whether propofol pretreatment can protect against liver transplantation-induced acute lung injury (ALI) and to explore whether Nrf2 pathway is involved in the protections provided by propofol pretreatment.Method. Adult male Sprague-Dawley rats were divided into five groups based on the random number table. Lung pathology was observed by optical microscopy. Lung water content was assessed by wet/dry ratio, and PaO2was detected by blood gas analysis. The contents of H2O2, MDA, and SOD activity were determined by ELISA method, and the expression of HO-1, NQO1, Keap1, and nuclear Nrf2 was assayed by western blotting.Results. Compared with saline-treated model group, both propofol and N-acetylcysteine pretreatment can reduce the acute lung injury caused by orthotopic autologous liver transplantation (OALT), decrease the lung injury scores, lung water content, and H2O2and MDA levels, and improve the arterial PaO2and SOD activity. Furthermore, propofol (but not N-acetylcysteine) pretreatment especially in high dose inhibited the expression of Keap1 and induced translocation of Nrf2 into the nucleus to further upregulate the expression of HO-1 and NQO1 downstream.Conclusion. Pretreatment with propofol is associated with attenuation of OALT-induced ALI, and the Nrf2 pathway is involved in the antioxidative processes.

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

10.21203/rs.3.rs-1089681/v1 ◽

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.

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H2S Attenuates LPS-Induced Acute Lung Injury by Reducing Oxidative/Nitrative Stress and Inflammation

Cellular Physiology and Biochemistry ◽

10.1159/000453210 ◽

2016 ◽

Vol 40 (6) ◽

pp. 1603-1612 ◽

Cited By ~ 54

Author(s):

Hong-Xia Zhang ◽

Shu-Juan Liu ◽

Xiao-Lu Tang ◽

Guo-Li Duan ◽

Xin Ni ◽

...

Keyword(s):

Nitric Oxide ◽

Acute Lung Injury ◽

Treatment Group ◽

Lung Injury ◽

Control Group ◽

No Production ◽

Sod Activity ◽

Nitrative Stress ◽

Anti Oxidant ◽

Anti Inflammatory

Background: Hydrogen sulfide (H2S), known as the third endogenous gaseous transmitter, has received increasing attention because of its diverse effects, including angiogenesis, vascular relaxation and myocardial protection.We aimed to investigate the role of H2S in oxidative/nitrative stress and inflammation in acute lung injury (ALI) induced by endotoxemia. Methods: Male ICR mice were divided in six groups: (1) Control group; (2) GYY4137treatment group; (3) L-NAME treatment group; (4) lipopolysaccharide (LPS) treatment group; (5) LPS with GYY4137 treatment group; and (6) LPS with L-NAME treatment group. The lungs were analysed by histology, NO production in the mouse lungs determined by modified Griess (Sigma-Aldrich) reaction, cytokine levels utilizing commercialkits, and protein abundance by Western blotting. Results: GYY4137, a slowly-releasing H2S donor, improved the histopathological changes in the lungs of endotoxemic mice. Treatment with NG-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, increased anti-oxidant biomarkers such as thetotal antioxidant capacity (T-AOC) and theactivities of catalase (CAT) and superoxide dismutase (SOD) but decreased a marker of peroxynitrite (ONOO-) action and 3-nitrotyrosine (3-NT) in endotoxemic lung. L-NAME administration also suppressed inflammation in endotoxemic lung, as evidenced by the decreased pulmonary levels of interleukin (IL)-6, IL-8, and myeloperoxidase (MPO) and the increased level of anti-inflammatory cytokine IL-10. GYY4137 treatment reversed endotoxin-induced oxidative/nitrative stress, as evidenced by a decrease in malondialdehyde (MDA), hydrogenperoxide (H2O2) and 3-NT and an increase in the antioxidant biomarker ratio of reduced/oxidized glutathione(GSH/GSSG ratio) and T-AOC, CAT and SOD activity. GYY4137 also attenuated endotoxin-induced lung inflammation. Moreover, treatment with GYY4137 inhibited inducible NOS (iNOS) expression and nitric oxide (NO) production in the endotoxemia lung. Conclusions: GYY4137 conferred protection against acute endotoxemia-associated lung injury, which may have beendue to the anti-oxidant, anti-nitrative and anti-inflammatory properties of GYY4137. The present findings warrant further exploration of the clinical applicability of H2S in the prevention and treatment of ALI.

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Anti-inflammatory effects of curcumin in acute lung injury: In vivo and in vitro experimental model studies

International Immunopharmacology ◽

10.1016/j.intimp.2021.107600 ◽

2021 ◽

Vol 96 ◽

pp. 107600

Author(s):

Yang Wang ◽

Yujuan Wang ◽

Nan Cai ◽

Tianshu Xu ◽

Fei He

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Experimental Model ◽

Model Studies ◽

Anti Inflammatory

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

Infection and Immunity ◽

10.1128/iai.00301-21 ◽

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.

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Design, synthesis and bioactivity evaluation of fisetin derivatives as potential anti-inflammatory agents against LPS-induced acute lung injury

Bioorganic & Medicinal Chemistry ◽

10.1016/j.bmc.2021.116456 ◽

2021 ◽

pp. 116456

Author(s):

Xiemin Wang ◽

Jun Yang ◽

Bingyu Ding ◽

Pan Chen ◽

Zhengwei Xu ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Design Synthesis ◽

Anti Inflammatory

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

Pharmacognosy Magazine ◽

10.4103/pm.pm_448_20 ◽

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

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GBT1118, a compound that increases the oxygen affinity of hemoglobin, improves survival in murine hypoxic acute lung injury

Journal of Applied Physiology ◽

10.1152/japplphysiol.00079.2017 ◽

2018 ◽

Vol 124 (4) ◽

pp. 899-905 ◽

Cited By ~ 2

Author(s):

Nathan D. Putz ◽

Ciara M. Shaver ◽

Kobina Dufu ◽

Chien-Ming Li ◽

Qing Xu ◽

...

Keyword(s):

Acute Respiratory Distress Syndrome ◽

Acute Lung Injury ◽

Lung Injury ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Distress Syndrome ◽

Oxygen Affinity ◽

High Dose ◽

Novel Therapy ◽

Oxygen Affinity Of Hemoglobin

Acute respiratory distress syndrome (ARDS) is characterized by lung inflammation and pulmonary edema, leading to arterial hypoxemia and death if the hypoxemia is severe. Strategies to correct hypoxemia have the potential to improve clinical outcomes in ARDS. The goal of this study was to evaluate the potential of hemoglobin modification as a novel therapy for ARDS-induced hypoxemia. The therapeutic effect of two different doses of GBT1118, a compound that increases the oxygen affinity of hemoglobin, was evaluated in a murine model of acute lung injury induced by intratracheal LPS instillation 24 h before exposure to 5% or 10% hypoxia ( n = 8–15 per group). As expected, administration of GBT1118 to mice significantly increased the oxygen affinity of hemoglobin. Compared with mice receiving vehicle control, mice treated with GBT1118 had significantly lower mortality after LPS + 5% hypoxia (47% with vehicle vs. 22% with low-dose GBT1118, 13% with high-dose GBT1118, P = 0.032 by log rank) and had reduced severity of illness. Mice treated with GBT1118 showed a sustained significant increase in SpO2 over 4 h of hypoxia exposure. Treatment with GBT1118 did not alter alveolar-capillary permeability, bronchoalveolar lavage (BAL) inflammatory cell counts, or BAL concentrations of IL-1β, TNF-α, or macrophage inflammatory protein-1α. High-dose GBT1118 did not affect histological lung injury but did decrease tissue hypoxia as measured intensity of pimonidazole (Hypoxyprobe) staining in liver ( P = 0.043) and kidney ( P = 0.043). We concluded that increasing the oxygen affinity of hemoglobin using GBT1118 may be a novel therapy for treating hypoxemia associated with acute lung injury. NEW & NOTEWORTHY In this study, we show that GBT1118, a compound that increases hemoglobin affinity for oxygen, improves survival and oxygen saturation in a two-hit lung injury model of intratracheal LPS without causing tissue hypoxia. Modulation of hemoglobin oxygen affinity represents a novel therapeutic approach to treatment of acute lung injury and acute respiratory distress syndrome, conditions characterized by hypoxemia.

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Vanillin protects lipopolysaccharide-induced acute lung injury by inhibiting ERK1/2, p38 and NF-κB pathway

Future Medicinal Chemistry ◽

10.4155/fmc-2018-0432 ◽

2019 ◽

Vol 11 (16) ◽

pp. 2081-2094 ◽

Cited By ~ 1

Author(s):

Tingting Guo ◽

Zhenzhong Su ◽

Qi Wang ◽

Wei Hou ◽

Junyao Li ◽

...

Keyword(s):

Acute Lung Injury ◽

Lung Injury ◽

Western Blot ◽

Lung Inflammation ◽

Macrophage Activation ◽

Myeloperoxidase Activity ◽

Histopathological Changes ◽

Tnf Α ◽

Anti Inflammatory ◽

Inflammatory Effect

Aim: Thus far, the anti-inflammatory effect of vanillin in acute lung injury (ALI) has not been studied. This study aimed to investigate the effect of vanillin in lipopolysaccharide (LPS)-induced ALI. Results & methodology: Our study detected the anti-inflammatory effects of vanillin by ELISA and western blot, respectively. Pretreatment of mice with vanillin significantly attenuated LPS-stimulated lung histopathological changes, myeloperoxidase activity and expression levels of proinflammatory cytokines by inhibiting the phosphorylation activities of ERK1/2, p38, AKT and NF-κB p65. In addition, vanillin inhibited LPS-induced TNF-α and IL-6 expression in RAW264.7 cells via ERK1/2, p38 and NF-κB signaling. Conclusion: Vanillin can inhibit macrophage activation and lung inflammation, which suggests new insights for clinical treatment of ALI.

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