scholarly journals Maraviroc-Mediated Lung Protection following Trauma-Hemorrhagic Shock

2016 ◽  
Vol 2016 ◽  
pp. 1-8
Author(s):  
Fu-Chao Liu ◽  
Chih-Wen Zheng ◽  
Huang-Ping Yu
Keyword(s):  
Water Content ◽  
Interleukin 1 ◽  
Intercellular Adhesion Molecule ◽  
Myeloperoxidase Activity ◽  
Sprague Dawley ◽  
Intercellular Adhesion Molecule 1 ◽  
Lung Water ◽  
Lung Protection ◽  
Anti Inflammatory ◽  
Lung Water Content

Objectives.The peroxisome proliferator-activated receptor gamma (PPARγ) pathway exerts anti-inflammatory effects in response to injury. Maraviroc has been shown to have potent anti-inflammatory effects. The aim of this study was to investigate whether PPARγplays an important role in maraviroc-mediated lung protection following trauma-hemorrhage.Methods.Male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure maintained at approximately 35–40 mmHg for 90 minutes), followed by fluid resuscitation. During resuscitation, a single dose of maraviroc (3 mg/kg, intravenously) with and without a PPARγinhibitor GW9662 (1 mg/kg, intravenously), GW9662, or vehicle was administered. Lung water content, tissue histology, and other various parameters were measured (n=8rats/group) 24 hours after resuscitation. One-way ANOVA and Tukey’s testing were used for statistical analysis.Results.Trauma-hemorrhage significantly increased lung water content, myeloperoxidase activity, intercellular adhesion molecule-1, interleukin-6, and interleukin-1βlevels. These parameters significantly improved in the maraviroc-treated rats subjected to trauma-hemorrhage. Maraviroc treatment also decreased lung tissue damage as compared to the vehicle-treated trauma-hemorrhaged rats. Coadministration of GW9662 with maraviroc abolished the maraviroc-induced beneficial effects on these parameters and lung injury.Conclusion.These results suggest that PPARγmight play a key role in maraviroc-mediated lung protection following trauma-hemorrhage.

scholarly journals Gadolinium Chloride Attenuates Sepsis-Induced Pulmonary Apoptosis and Acute Lung Injury

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Osama A. Kishta ◽  
Peter Goldberg ◽  
Sabah N. A. Husain
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Water Content ◽  
Interleukin 1 ◽  
Gadolinium Chloride ◽  
Myeloperoxidase Activity ◽  
Mrna Levels ◽  
Lung Water ◽  
Pre Treatment ◽  
Lung Water Content

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.

A2A adenosine receptor-mediated inhibition of renal injury and neutrophil adhesion

2000 ◽  
Vol 279 (5) ◽  
pp. F809-F818 ◽  
Author(s):  
Mark D. Okusa ◽  
Joel Linden ◽  
Liping Huang ◽  
Jayson M. Rieger ◽  
Timothy L. Macdonald ◽  
...  
Keyword(s):  
Renal Injury ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Plasma Creatinine ◽  
Intercellular Adhesion Molecule ◽  
Neutrophil Adhesion ◽  
Myeloperoxidase Activity ◽  
Sprague Dawley ◽  
Intercellular Adhesion Molecule 1 ◽  
Peritubular Capillaries

We sought to determine the mechanisms responsible for the reduced renal tissue injury by agonists of A2A adenosine receptors (A2A-ARs) in models of ischemia-reperfusion (I/R) injury. DWH-146e, a selective A2A-AR agonist, was administered subcutaneously to Sprague-Dawley rats and C57BL/6 mice via osmotic minipumps, and animals were subjected to I/R. I/R led to an increase in plasma creatinine and kidney neutrophil infiltration. Infusion of DWH-146e at 10 ng · kg−1 · min−1 produced a 70% reduction in plasma creatinine as well as a decrease in neutrophil density in outer medulla and cortex and myeloperoxidase activity in the reperfused kidney. Myeloperoxidase activity in kidney correlated with the degree of renal injury. P-selectin and intercellular adhesion molecule 1 (ICAM-1) immunoreactivity were most prominent in endothelial cells of peritubular capillaries and interlobular arteries of cortex and outer and inner medulla of vehicle-treated mice whose kidneys were subjected to I/R. DWH-146e treatment led to a pronounced decrease in P-selectin- and ICAM-1-like immunoreactivity. These data are consistent with our hypothesis that A2A-AR agonists limit I/R injury due to an inhibitory effect on neutrophil adhesion.

Magnetic Resonance Imaging Spatial and Time Study of Lung Water Content in Newborn Lamb: Methods and Preliminary Results

2008 ◽  
Vol 43 (6) ◽  
pp. 470-480 ◽  
Author(s):  
Romain Viard ◽  
Pierre Tourneux ◽  
Laurent Storme ◽  
Julie-Marie Girard ◽  
Nacim Betrouni ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Water Content ◽  
Time Study ◽  
Resonance Imaging ◽  
Lung Water ◽  
Newborn Lamb ◽  
Preliminary Results ◽  
Lung Water Content

ICAM-1 and P-selectin expression in a model of NSAID-induced gastropathy

1998 ◽  
Vol 274 (2) ◽  
pp. G246-G252 ◽  
Author(s):  
Z. Morise ◽  
S. Komatsu ◽  
J. W. Fuseler ◽  
D. N. Granger ◽  
M. Perry ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Critical Role ◽  
Mucosal Blood Flow ◽  
Gastric Mucosal Blood Flow ◽  
Mucosal Injury ◽  
Gastric Mucosal Injury ◽  
Intercellular Adhesion Molecule ◽  
Sprague Dawley ◽  
Intercellular Adhesion Molecule 1 ◽  
Mucosal Permeability

A growing body of experimental evidence suggests that neutrophilic polymorphonuclear leukocyte (PMN)-endothelial cell interactions play a critical role in the pathophysiology of nonsteroidal anti-inflammatory drug (NSAID)-induced gastropathy. The objective of this study was to directly determine whether the expression of endothelial cell adhesion molecules is enhanced in a model of NSAID-induced gastropathy. Gastropathy was induced in male Sprague-Dawley rats via oral administration of indomethacin (Indo, 20 mg/kg). Lesion scores, blood-to-lumen clearance of 51Cr-EDTA (mucosal permeability), and histological analysis (epithelial necrosis) were used as indexes of gastric mucosal injury. Gastric mucosal vascular expression of intercellular adhesion molecule 1 (ICAM-1) or P-selectin were determined at 1 and 3 h after Indo administration using the dual radiolabeled monoclonal antibody (MAb) technique. For some experiments, a blocking MAb directed at either ICAM-1 (1A29) or P-selectin (RMP-1) or their isotype-matched controls was injected intravenously 10 min before Indo administration. We found that P-selectin expression was significantly increased at 1 h but not 3 h after Indo administration, whereas ICAM-1 expression was significantly increased at both 1 and 3 h after Indo treatment. The blocking ICAM-1 and P-selectin MAbs both inhibited Indo-induced increases in lesion score, mucosal permeability, and epithelial cell necrosis. However, the Indo-induced gastropathy was not associated with significant PMN infiltration into the gastric mucosal interstitium, nor did Indo reduce gastric mucosal blood flow. We propose that NSAID-induced gastric mucosal injury may be related to the expression of P-selectin and ICAM-1; however, this mucosal injury does not appear to be dependent on the extravasation of inflammatory cells or mucosal ischemia.

A novel role for E- and P-selectins: shape control of endothelial cell monolayers

1994 ◽  
Vol 107 (9) ◽  
pp. 2449-2457 ◽  
Author(s):  
G. Kaplanski ◽  
C. Farnarier ◽  
A.M. Benoliel ◽  
C. Foa ◽  
S. Kaplanski ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Shape Control ◽  
Interleukin 1 ◽  
Cytosolic Calcium ◽  
Intercellular Adhesion Molecule ◽  
Initial Contact ◽  
Calcium Stores ◽  
Main Role ◽  
Intercellular Adhesion Molecule 1 ◽  
Peripheral Tissues

The migration of neutrophils from blood vessels to peripheral tissues is a key step of inflammation. This requires the formation of transient gaps between endothelial cells with concomitant leucocyte squeezing through these narrow apertures and immediate restoration of endothelium continuity. It is currently considered that the main role of selectins is to mediate the initial contact between flowing leucocytes and endothelial cells. We show here that the binding of E- or P-selectins by specific antibodies induces a marked ‘rounding up’ of interleukin-1- or thrombin-activated human endothelial cells, respectively. Also, anti-E-selectin antibodies trigger a transient increase in cytosolic calcium involving intracellular calcium stores. No such effect is observed when von Willebrand factor or intercellular adhesion molecule 1 are similarly bound. Thus, in addition to promoting the initial interaction between activated endothelium and moving leucocytes, selectins might play a role in the induction of subsequent endothelial deformation, which would facilitate leucocyte arrest and transmigration towards peripheral tissues, and enhance the diffusion of soluble molecules between intravascular and peripheral compartments. Our results are consistent with this hypothesis and demonstrate a new property of endothelial selectins.

Combined inhibition of P-selectin and ICAM-1 reduces myocardial injury following ischemia and reperfusion

1996 ◽  
Vol 271 (6) ◽  
pp. H2421-H2429 ◽  
Author(s):  
D. J. Lefer ◽  
D. M. Flynn ◽  
D. C. Anderson ◽  
A. J. Buda
Keyword(s):  
Blood Flow ◽  
Monoclonal Antibodies ◽  
Myocardial Blood Flow ◽  
Myocardial Protection ◽  
Coronary Artery Occlusion ◽  
Artery Occlusion ◽  
Intercellular Adhesion Molecule ◽  
Myeloperoxidase Activity ◽  
Intercellular Adhesion Molecule 1 ◽  
Neutrophil Accumulation

Neutrophil-endothelial cell interactions are mediated by a number of cell adhesion proteins. We investigated the effects of inhibition of P-selectin and intercellular adhesion molecule-1 (ICAM-1), individually or in combination, in the ischemic-reperfused canine myocardium. Monoclonal antibodies PB1.3 (anti-P-selectin) and CL 18/6 (anti-ICAM-1) were administered to dogs subjected to coronary artery occlusion and reperfusion. After reperfusion, untreated dogs experienced a 61% decline (P < 0.01 vs. baseline) in myocardial blood flow and a ninefold increase in ischemic zone neutrophil accumulation (4.7 +/- 0.9 U/100 mg tissue myeloperoxidase activity). In contrast, PB1.3 and CL 18/6 administered individually preserved myocardial blood flow (11 and 24% decrease from baseline, respectively, both P < 0.01 vs. saline), and significantly attenuated myeloperoxidase activity (1.4 +/- 0.3 and 1.5 +/- 0.26 U/100 mg tissue, respectively, both P < 0.01 vs. saline). PB1.3 and CL 18/6 in combination resulted in significant coronary vascular and myocardial protection that was not superior to treatment with either antibody alone. Thus the coadministration of anti-P-selectin and anti-ICAM-1 monoclonal antibodies does not enhance the degree of myocardial protection in this model of reperfusion injury.

scholarly journals Biochemical Evaluation of the Antioxidant Effects of Hydroxytyrosol on Pancreatitis-Associated Gut Injury

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 781 ◽  
Author(s):  
Roberta Fusco ◽  
Marika Cordaro ◽  
Rosalba Siracusa ◽  
Ramona D’Amico ◽  
Tiziana Genovese ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Interleukin 1 ◽  
Antioxidant Properties ◽  
Pancreatic Tissue ◽  
Intercellular Adhesion Molecule ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Intercellular Adhesion Molecule 1 ◽  
Colon Tissue ◽  
Necrosis Factor Alpha

Acute pancreatitis is a severe abdominal pathology often associated with several complications including gut dysfunction. Oxidative stress is one of the most important pathways involved in this pathology. Hydroxytyrosol (HT), a phenolic compound obtained from olive oil, has shown anti-inflammatory and antioxidant properties. We evaluated the effects of HT administration on pancreatic and intestinal injury induced by caerulein administration. CD1 female mice were administered caerulein (50 μg/kg) for 10 h. HT treatment (5 mg/kg) was performed 30 min after the first caerulein injection and for two consecutive hours afterwards. One hour after the last caerulein injection, mice were sacrificed and serum, colon and pancreatic tissue samples were collected. HT was able to reduce the serum hallmarks of pancreatitis (amylase and lipase), histological damage score in both pancreas and colon tissue, inflammatory cells recruitment (mast cells) in both injured tissues, intrapancreatic trypsin activity and overexpression of the adhesion molecules (Intercellular Adhesion Molecule-1 (ICAM-1) and P-selectin) in colon. Additionally, HT reduced cytokine (interleukin 1 beta (IL- 1β), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α)) levels in serum, pancreas and colon tissue and chemokine release (monocyte chemotactic protein-1 (MCP1/CCL2)) in pancreas and colon tissue. HT decreased lipid peroxidation and oxidative stress (superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) activity) by enhancing the nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in both injured tissues. Moreover, HT preserved intestinal barrier integrity, as shown by the diamine oxidase (DAO) serum levels and tight junction (zonula occludens (ZO) and occludin) expression in pancreas and colon. Our findings demonstrated that HT would be an important therapeutic tool against pancreatitis-induced injuries in the pancreas and gut.

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