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

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Weifeng Yao ◽  
Gangjian Luo ◽  
Guosong Zhu ◽  
Xinjin Chi ◽  
Ailan Zhang ◽  
...  

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.

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Osama A. Kishta ◽  
Peter Goldberg ◽  
Sabah N. A. Husain

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.


2010 ◽  
Vol 36 (12) ◽  
pp. 2004-2010 ◽  
Author(s):  
Zoltán Jambrik ◽  
Luna Gargani ◽  
Ágnes Adamicza ◽  
József Kaszaki ◽  
Albert Varga ◽  
...  

2021 ◽  
Author(s):  
harun un ◽  
Rustem Anil Ugan ◽  
duygu Köse ◽  
muhammed yayla ◽  
Tugba Bal Tastan ◽  
...  

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.


2008 ◽  
Vol 43 (6) ◽  
pp. 470-480 ◽  
Author(s):  
Romain Viard ◽  
Pierre Tourneux ◽  
Laurent Storme ◽  
Julie-Marie Girard ◽  
Nacim Betrouni ◽  
...  

2018 ◽  
Vol 124 (4) ◽  
pp. 899-905 ◽  
Author(s):  
Nathan D. Putz ◽  
Ciara M. Shaver ◽  
Kobina Dufu ◽  
Chien-Ming Li ◽  
Qing Xu ◽  
...  

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.


1999 ◽  
Vol 43 (10) ◽  
pp. 2389-2394 ◽  
Author(s):  
Erika J. Ernst ◽  
Satoru Hashimoto ◽  
Joseph Guglielmo ◽  
Teiji Sawa ◽  
Jean-Francois Pittet ◽  
...  

ABSTRACT The effect of antibiotics on the acute lung injury induced by virulent Pseudomonas aeruginosa PA103 was quantitatively analyzed in a rat model. Lung injury was induced by the instillation of PA103 directly into the right lower lobes of the lungs of anesthetized rats. The alveolar epithelial injury, extravascular lung water, and total plasma equivalents were measured as separate, independent parameters of acute lung injury. Four hours after the instillation of PA103, all the parameters were increased linearly depending on the dose of P. aeruginosa. Next, we examined the effects of intravenously administered antibiotics on the parameters of acute lung injury in d-galactosamine-sensitized rats. One hour after the rats received 107 CFU of PA103, an intravenous bolus injection of aztreonam (60 mg/kg) or imipenem-cilastatin (30 mg/kg) was administered. Despite an MIC indicating resistance, imipenem-cilastatin improved all the measurements of lung injury; in contrast, aztreonam, which had an MIC indicating sensitivity, did not improve any of the lung injury parameters. The antibiotics did not generate different quantities of plasma endotoxin; therefore, endotoxin did not appear to explain the differences in lung injury. This in vivo model is useful to quantitatively compare the efficacies of parenteral antibiotic administration on Pseudomonas airspace infections.


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