scholarly journals Metallothionein-induced zinc partitioning exacerbates hyperoxic acute lung injury

2013 ◽  
Vol 304 (5) ◽  
pp. L350-L360 ◽  
Author(s):  
Sang-Min Lee ◽  
Joseph N. McLaughlin ◽  
Daniel R. Frederick ◽  
Lin Zhu ◽  
Kalidasan Thambiayya ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Zinc Homeostasis ◽  
Sod Activity ◽  
Resistant Phenotype ◽  
Distal Airway ◽  
Injury Mechanisms ◽  
Hyperoxic Lung Injury ◽  
Copper Zinc ◽  
Genetic Deletion

Hypozincemia, with hepatic zinc accumulation at the expense of other organs, occurs in infection, inflammation, and aseptic lung injury. Mechanisms underlying zinc partitioning or its impact on extrahepatic organs are unclear. Here we show that the major zinc-binding protein, metallothionein (MT), is critical for zinc transmigration from lung to liver during hyperoxia and preservation of intrapulmonary zinc during hyperoxia is associated with an injury-resistant phenotype in MT-null mice. Particularly, lung-to-liver zinc ratios decreased in wild-type (WT) and increased significantly in MT-null mice breathing 95% oxygen for 72 h. Compared with female adult WT mice, MT-null mice were significantly protected against hyperoxic lung injury indicated by reduced inflammation and interstitial edema, fewer necrotic changes to distal airway epithelium, and sustained lung function at 72 h hyperoxia. Lungs of MT-null mice showed decreased levels of immunoreactive LC3, an autophagy marker, compared with WT mice. Analysis of superoxide dismutase (SOD) activity in the lungs revealed similar levels of manganese-SOD activity between strains under normoxia and hyperoxia. Lung extracellular SOD activity decreased significantly in both strains at 72 h of hyperoxia, although there was no difference between strains. Copper-zinc-SOD activity was ∼4× higher under normoxic conditions in MT-null compared with WT mice but was not affected in either group by hyperoxia. Collectively the data suggest that genetic deletion of MT-I/II in mice is associated with compensatory increase in copper-zinc-SOD activity, prevention of hyperoxia-induced zinc transmigration from lung to liver, and hyperoxia-resistant phenotype strongly associated with differences in zinc homeostasis during hyperoxic acute lung injury.

scholarly journals Natural Antioxidant Betanin Protects Rats from Paraquat-Induced Acute Lung Injury Interstitial Pneumonia

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Junyan Han ◽  
Deshun Ma ◽  
Miao Zhang ◽  
Xuelian Yang ◽  
Dehong Tan
Keyword(s):  
Body Weight ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Weight Ratio ◽  
Lavage Fluid ◽  
Dependent Manner ◽  
Sod Activity ◽  
Protein Levels ◽  
Injury Characteristic ◽  
Dose Dependent

The effect of betanin on a rat paraquat-induced acute lung injury (ALI) model was investigated. Paraquat was injected intraperitoneally at a single dose of 20 mg/kg body weight, and betanin (25 and 100 mg/kg/d) was orally administered 3 days before and 2 days after paraquat administration. Rats were sacrificed 24 hours after the last betanin dosage, and lung tissue and bronchoalveolar lavage fluid (BALF) were collected. In rats treated only with paraquat, extensive lung injury characteristic of ALI was observed, including histological changes, elevation of lung : body weight ratio, increased lung permeability, increased lung neutrophilia infiltration, increased malondialdehyde (MDA) and myeloperoxidase (MPO) activity, reduced superoxide dismutase (SOD) activity, reduced claudin-4 and zonula occluden-1 protein levels, increased BALF interleukin (IL-1) and tumor necrosis factor (TNF)-αlevels, reduced BALF IL-10 levels, and increased lung nuclear factor kappa (NF-κB) activity. In rats treated with betanin, paraquat-induced ALI was attenuated in a dose-dependent manner. In conclusion, our results indicate that betanin attenuates paraquat-induced ALI possibly via antioxidant and anti-inflammatory mechanisms. Thus, the potential for using betanin as an auxilliary therapy for ALI should be explored further.

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 ◽  
...  
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.

scholarly journals Amentoflavone prevents sepsis-associated acute lung injury through Nrf2-GCLc-mediated upregulation of glutathione

2016 ◽  
Vol 64 (1) ◽  
Author(s):  
Yuan Zong ◽  
Huali Zhang
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Lung Tissue ◽  
Medical Problem ◽  
Binding Activity ◽  
Content Increase ◽  
Protective Effects ◽  
Sod Activity ◽  
Buthionine Sulphoximine

Sepsis is a serious medical problem that is one of the main causes of high mortality in intensive care units. Fifty percent of patients with severe sepsis will develop acute lung injury (ALI). Amentoflavone (AMF) is a polyphenolic compound possessing potent anti-inflammatory activities. The present study was designed to explore the protective effects of AMF against ALI in CLP-induced septic rats. The results showed that AMF administration protected against septic ALI, as reflected by marked amelioration of histological injury of lung tissues and decrease of pulmonary edema in CLP-treated rats. AMF ameliorated CLP-induced increase of systemic and lung TNF-α and IL-1β and the binding activity of p65 NF-κB, indicating the inhibition of inflammation induced by CLP. Moreover, AMF prevented CLP-induced oxidative stress, as evidenced by increase of oxygen consumption rate, decrease of TBARS content, increase of SOD activity and GSH level in lung tissue of CLP-treated rats. CLP resulted in significant decrease of mRNA expression of Nrf2 and GCLc, which was inhibited by AMF. AMF-induced protective effects on ALI, inflammation, and oxidative stress were inhibited by lentivirus-mediated shRNA of Nrf2 and buthionine sulphoximine (BSO), an inhibitor of GSH synthesis. AMF increased Nrf2-binding activity with GCLc promoters in lung tissue of CLP-treated rats. The results suggested that AMF protected against ALI in septic rats through upregulation of Nrf2-GCLc signaling, enhancement of GSH antioxidant defense, reduction of oxidative stress and final amelioration of inflammation and histological injury of lung. The data provide new therapeutic options for the treatment of sepsis-associated ALI.

scholarly journals The Roles of Autophagy in Acute Lung Injury Induced by Myocardial Ischemia Reperfusion in Diabetic Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Liying Zhan ◽  
Yuan Zhang ◽  
Wating Su ◽  
Qiongxia Zhang ◽  
Rong Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Myocardial Ischemia ◽  
Lung Injury ◽  
Ischemia Reperfusion ◽  
Diabetic Rats ◽  
Lung Injury Score ◽  
Sod Activity ◽  
Autophagy Inhibitor ◽  
Myocardial Ischemia Reperfusion

Patients with diabetes are vulnerable to myocardial ischemia reperfusion (IR) injury, which may also induce acute lung injury (ALI) due to overaccumulation of reactive oxygen species (ROS) and inflammation cytokine in circulation. Despite autophagy plays a significant role in diabetes and pulmonary IR injury, the role of autophagy in ALI secondary to myocardial IR in diabetes remains largely elusive. We aimed to investigate pulmonary autophagy status and its roles in oxidative stress and inflammation reaction in lung tissues from diabetic rats subjected to myocardial IR. Control or diabetic rats were either treated with or without autophagy inducer rapamycin (Rap) or autophagy inhibitor 3-methyladenine (3-MA) before myocardial IR, which was achieved by occluding the left anterior descending coronary artery for 30 min and followed by reperfusion for 120 min. Diabetic rats subjected to myocardial IR showed more serious ALI with higher lung injury score and WET/DRY ratio and lower PaO2 as compared with control rats, accompanied with impaired autophagy indicated by reduced LC-3II/LC-3I ratio and Beclin-1 expression, decreased superoxide dismutase (SOD) activity, and increased 15-F2t-Isoprostane formation in lung tissues, as well as increased levels of leukocyte count and proinflammatory cytokines in BAL fluid. Improving autophagy with Rap significantly attenuated all these changes, but the autophagy inhibitor 3-MA exhibited adverse or opposite effects as Rap. In conclusion, diabetic lungs are more vulnerable to myocardial IR, which are involved in impaired autophagy. Improving autophagy could attenuate ALI induced by myocardial IR in diabetic rats, possibly through inhibiting inflammatory reaction and oxidative stress.

scholarly journals Remote Inflammatory Preconditioning Alleviates Lipopolysaccharide-Induced Acute Lung Injury via Inhibition of Intrinsic Apoptosis in Rats

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Yong Liu ◽  
Jiahang Xu ◽  
Liang Zhao ◽  
Jing Cheng ◽  
Baojun Chen
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Animal Experiments ◽  
Intrinsic Apoptosis ◽  
Sprague Dawley ◽  
Sod Activity ◽  
Lung Protection ◽  
Sprague Dawley Rats ◽  
The Right

Background. Acute lung injury (ALI) always leads to severe inflammation. As inflammation and oxidative stress are the common pathological basis of endotoxin-induced inflammatory injury and ischemic reperfusion injury (IRI), we speculate that remote ischemic preconditioning (RIPC) can be protective for ALI when used as remote inflammatory preconditioning (RInPC). Method. A total of 21 Sprague-Dawley rats were used for the animal experiments. Eighteen rats were equally and randomly divided into the control (NS injection), LPS (LPS injection), and RInPC groups. The RInPC was performed prior to the LPS injection via tourniquet blockage of blood flow to the right hind limb and adopted three cycles of 5 min tying followed by 5 min untying. Animals were sacrificed 24 hours later. There were 2 rats in the LPS group and 1 in the RInPC group who died before the end of the experiment. Supplementary experiments in the LPS and RInPC groups were conducted to ensure that 6 animals in each group reached the end of the experiment. Results. In the present study, we demonstrated that the RInPC significantly attenuated the LPS-induced ALI in rats. Apoptotic cells were reduced significantly by the RInPC, with the simultaneous improvement of apoptosis-related proteins. Reduction of MPO and MDA and increasing of SOD activity were found significantly improved by the RInPC. Increasing of TNF-α, IL-1β, and IL-6 induced by the LPS was inhibited, while IL-10 was significantly increased by RInPC, compared to the LPS group. Conclusion. RInPC could inhibit inflammation and attenuate oxidative stress, thereby reducing intrinsic apoptosis and providing lung protection in the LPS-induced ALI in rats.

Mechanisms of interaction between oxygen and granulocytes in hyperoxic lung injury

1985 ◽  
Vol 58 (4) ◽  
pp. 1326-1330 ◽  
Author(s):  
B. P. Krieger ◽  
W. H. Loomis ◽  
G. T. Czer ◽  
R. G. Spragg
Keyword(s):  
Lipid Peroxidation ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Bronchoalveolar Lavage ◽  
Chemotactic Activity ◽  
Lung Edema ◽  
High Permeability ◽  
Rabbit Lung ◽  
Hyperoxic Lung Injury ◽  
Lung Lipid

Hyperoxia and infused granulocytes act synergistically in producing a nonhydrostatic high-permeability lung edema in the isolated perfused rabbit lung within 4 h, which is substantially greater than that seen with hyperoxia alone. We hypothesized that the interaction between hyperoxia and granulocytes was principally due to a direct effect of hyperoxia on the lung itself. Isolated perfused rabbit lungs that were preexposed to 2 h of hyperoxia (95% O2–5% CO2) prior to the infusion of unstimulated granulocytes (under normoxic conditions) developed significant nonhydrostatic lung edema (P = 0.008) within 2 h when compared with lungs that were preexposed to normoxia (15% O2–5% CO2) prior to granulocyte perfusion. The edema in the hyperoxic-preexposed lungs was accompanied by significant increases in bronchoalveolar lavage (BAL) protein, BAL granulocytes, BAL thromboxane and prostacyclin levels, perfusate chemotactic activity, and lung lipid peroxidation. These findings suggest that the synergistic interaction between hyperoxia and granulocytes in producing acute lung injury involves a primary effect of hyperoxia on the lung itself.

From Acute Pancreatitis to End-Organ Injury: Mechanisms of Acute Lung Injury

2007 ◽  
Vol 8 (1) ◽  
pp. 107-120 ◽  
Author(s):  
Tercio De Campos ◽  
Jessica Deree ◽  
Raul Coimbra
Keyword(s):  
Acute Pancreatitis ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Organ Injury ◽  
Injury Mechanisms

scholarly journals Akap1 genetic deletion increases the severity of hyperoxia-induced acute lung injury in mice

2018 ◽  
Vol 314 (5) ◽  
pp. L860-L870 ◽  
Author(s):  
Venkata Ramireddy Narala ◽  
Jutaro Fukumoto ◽  
Helena Hernández-Cuervo ◽  
Sahebgowda Sidramagowda Patil ◽  
Sudarshan Krishnamurthy ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Immune Cell ◽  
Cardiac Injury ◽  
Alveolar Epithelial Cells ◽  
Lung Damage ◽  
Alveolar Epithelial ◽  
Hypoxic Conditions ◽  
Anchoring Protein ◽  
Genetic Deletion

Critically ill patients are commonly treated with high levels of oxygen, hyperoxia, for prolonged periods of time. Unfortunately, extended exposure to hyperoxia can exacerbate respiratory failure and lead to a high mortality rate. Mitochondrial A-kinase anchoring protein (Akap) has been shown to regulate mitochondrial function. It has been reported that, under hypoxic conditions, Akap121 undergoes proteolytic degradation and promotes cardiac injury. However, the role of Akap1 in hyperoxia-induced acute lung injury (ALI) is largely unknown. To address this gap in our understanding of Akap1, we exposed wild-type ( wt) and Akap1−/− mice to 100% oxygen for 48 h, a time point associated with lung damage in the murine model of ALI. We found that under hyperoxia, Akap1−/− mice display increased levels of proinflammatory cytokines, immune cell infiltration, and protein leakage in lungs, as well as increased alveolar capillary permeability compared with wt controls. Further analysis revealed that Akap1 deletion enhances lung NF-κB p65 activity as assessed by immunoblotting and DNA-binding assay and mitochondrial autophagy-related markers, PINK1 and Parkin. Ultrastructural analysis using electron microscopy revealed that Akap1 deletion was associated with remarkably aberrant mitochondria and lamellar bodies in type II alveolar epithelial cells. Taken together, these results demonstrate that Akap1 genetic deletion increases the severity of hyperoxia-induced acute lung injury in mice.

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

2016 ◽  
Vol 40 (6) ◽  
pp. 1603-1612 ◽  
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.

Sign in / Sign up

Export Citation Format

Share Document