scholarly journals Terlipressin inhibits in vivo aortic iNOS expression induced by lipopolysaccharide in rats with biliary cirrhosis

Hepatology ◽  
2002 ◽  
Vol 36 (5) ◽  
pp. 1070-1078 ◽  
Author(s):  
Richard Moreau ◽  
Eric Barrière ◽  
Khalid A. Tazi ◽  
Bernard Lardeux ◽  
Delphine Dargère ◽  
...  
Keyword(s):  
Inos Expression ◽  
Biliary Cirrhosis

scholarly journals In vivo total body water assessment by total body electrical conductivity in rats suffering perturbations of water compartment equilibrium

1993 ◽  
Vol 70 (2) ◽  
pp. 433-438 ◽  
Author(s):  
N. Battistini ◽  
F. Virgili ◽  
G. Bedogni ◽  
G. R. Gambella ◽  
A. Bini
Keyword(s):  
Electrical Conductivity ◽  
Total Body Water ◽  
Body Water ◽  
Biliary Cirrhosis ◽  
Least Squares Regression ◽  
Water Compartment ◽  
Invasive Method ◽  
Total Body ◽  
Highly Correlated

Total body electrical conductivity (TOBEC) is a simple and non-invasive method for the assessment of body composition in vivo. Information regarding the applicability of TOBEC in the condition of abnormal fluid balance is scarce. In the present paper we give the results of the comparison between TOBEC and total body water (TBW; assessed by the tritium dilution technique) in three groups of animals: (1) healthy (n 17), (2) expanded fluid volume by secondary biliary cirrhosis (SBC; n 9) and (3) Fiirosemide®-treated rats (n 9). The TOBEC score and TBW by tritium dilution were found to be highly correlated in the pooled sample (r 0·90) and in normal (r 0.·87), SBC (r 0·73) and Furosemide-treated (r 0·89) rats. However, the relationship between TOBEC and TBW, described by least-squares regression analysis, was found to be similar for SBC and normal rats but was significantly different for Furosemide-treated and normal rats. These findings suggest that TOBEC is unable to track TBW accurately when the ratio between intracellular and extracellular water is chronically or acutely altered.

Abstract 28: Increased Expression Of Mitochondrial Inducible Nitric Oxide Synthase By Heat Shock Protein Hsp22/h11 Kinase Promotes Oxidative Phosphorylation In Mammalian Heart

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Hongyu Qiu ◽  
Eman Rashed ◽  
Christophe Depre
Keyword(s):  
Nitric Oxide ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Inos Expression ◽  
Mitochondrial Localization ◽  
Over Expression ◽  
Mitochondrial Translocation ◽  
Oxide Synthase ◽  
Stimulation Of

Aims: Stress-inducible heat shock protein 22 (Hsp22) confers protection against ischemia through induction of the inducible isoform of nitric oxide synthase (iNOS). Hsp22 over-expression in vivo significantly stimulates cardiac mitochondrial respiration, whereas Hsp22 deletion in vivo shows a reciprocal effect. It has also been shown in Drosophila that Hsp22 is expressed in the mitochondria that depends on its N-terminal domain. We hypothesized that Hsp22-mediated regulation of mitochondrial function is dependent upon its mitochondrial translocation together with iNOS. Methods and Results: Adenoviruses harboring either the full coding sequence of Hsp22 (Ad-WT-Hsp22) or a mutant lacking a 20 amino acid putative N-terminal mitochondrial localization sequence (Ad-N20-Hsp22) were generated, and infected in rat neonatal cardiomyocytes. Compared to β-Gal control, Ad-WT-Hsp22 accumulated in mitochondria by 2.5 fold (P<0.05), reduced chelerythrine-induced apoptosis by 60% (P<0.01), and increased oxygen consumption rate by 2-fold (P<0.01). This latter effect was abolished upon addition of the specific iNOS inhibitor, 1400W. Ad-WT-Hsp22 significantly increased global iNOS expression by about 2-fold (P<0.01), and also increased its mitochondrial localization by 2.5 fold vs β-gal (P<0.05). Upon comparable over-expression, the Ad-N20-Hsp22 mutant did not show significant mitochondrial translocation, protection against apoptosis or stimulation of mitochondrial respiration. Although Ad-N20-Hsp22 did increase global iNOS expression by 6-fold it did not significantly promote iNOS mitochondrial translocation. Conclusion: Translocation of both Hsp22 and iNOS to the mitochondria is necessary for the stimulation of oxidative metabolism and protection against apoptosis.

Differential alteration of cytochrome P450 isoenzymes in two experimental models of cirrhosis

2000 ◽  
Vol 78 (11) ◽  
pp. 912-919 ◽  
Author(s):  
Marie-Claude Bastien ◽  
François Leblond ◽  
Vincent Pichette ◽  
Jean-Pierre Villeneuve
Keyword(s):  
Cytochrome P450 ◽  
Carbon Tetrachloride ◽  
Bile Duct ◽  
Serum Albumin ◽  
Breath Test ◽  
Bile Duct Ligation ◽  
Biliary Cirrhosis ◽  
Breath Tests ◽  
Duct Ligation

Liver diseases are associated with a decrease in hepatic drug elimination, but there is evidence that cirrhosis does not result in uniform changes of cytochrome P450 (CYP) isoenzymes. The objective of this study was to determine the content and activity of four CYP isoenzymes in the bile duct ligation and carbon tetrachloride (CCl4)-induced models of cirrhosis. The hepatic content of CYP1A, CYP2C, CYP2E1, and CYP3A was measured by Western blot analysis. CYP activity in vivo was evaluated with breath tests using substrates specific for different isoenzymes: caffeine (CYP1A2), aminopyrine (CYP2C11), nitrosodimethylamine (CYP2E1), and erythromycin (CYP3A). Bile duct ligation resulted in biliary cirrhosis; CYP1A, CYP2C and CYP3A content was decreased and the caffeine, aminopyrine, and erythromycin breath tests were reduced whereas CYP2E1 content and the nitrosodimethylamine breath test were unchanged compared with controls. CCl4 treatment resulted in cirrhosis of varying severity as assessed from the decrease in liver weight and serum albumin. In rats with mild cirrhosis, CYP content was comparable with controls except for a decrease in CYP2C. The activity of CYPs was also unchanged except for an increase in CYP2E1 activity. In rats with more severe cirrhosis, the content of all four CYP isoenzymes and the caffeine, aminopyrine, and erythromycin breath tests were reduced whereas the nitrosodimethylamine breath test was unchanged. In both models of cirrhosis, there was a significant correlation between the breath tests results and the severity of cirrhosis as assessed from serum albumin levels. These results indicate that content and the catalytic activity of individual CYP enzymes are differentially altered by cirrhosis in the rat and also suggest that drug probes could be useful to assess hepatic functional reserve.Key words: breath test, cirrhosis, cytochrome P450, bile duct ligation, carbon tetrachloride.

Systemic NO production during (septic) shock depends on parenchymal and not on hematopoietic cells: in vivo iNOS expression pattern in (septic) shock

2006 ◽  
Vol 20 (13) ◽  
pp. 2363-2365 ◽  
Author(s):  
Jennyfer Bultinck ◽  
Patrick Sips ◽  
Luc Vakaet ◽  
Peter Brouckaert ◽  
Anje Cauwels ◽  
...  
Keyword(s):  
Septic Shock ◽  
Expression Pattern ◽  
Hematopoietic Cells ◽  
Inos Expression ◽  
No Production

Specific iNOS-targeted antisense knockdown in endothelial cells

2003 ◽  
Vol 285 (2) ◽  
pp. C489-C498 ◽  
Author(s):  
Karsten Hemmrich ◽  
Christoph V. Suschek ◽  
Guido Lerzynski ◽  
Oliver Schnorr ◽  
Victoria Kolb-Bachofen
Keyword(s):  
Endothelial Cells ◽  
Antisense Oligonucleotides ◽  
Inos Expression ◽  
Inos Mrna ◽  
Inflammatory Conditions ◽  
Antisense Knockdown ◽  
Oxide Synthase ◽  
The Impact ◽  
Inducible Nitric Oxide

The inhibition of inducible nitric oxide synthase (iNOS) expression via antisense oligonucleotides (AS-ODN) may represent a highly specific tool. Endothelial cells (EC) represent prime candidate cells for in vivo application, and we therefore aimed at optimizing this technique for effectiveness and specificity in primary nontransformed rat EC. EC or L929 fibroblasts were incubated with iNOS-specific ODN optimizing all experimental steps. We find that ODN uptake, as analyzed by fluorescence microscopy and labeled ODN, was absolutely dependent on vehicle presence, and among the vehicles tested, Lipofectin displayed negligible toxicity and good uptake. In addition, omission of serum was also essential, a factor that might limit its use in vivo. Moreover, intranuclear accumulation of AS-ODN appeared crucial for successive inhibition. The impact of ODN on iNOS mRNA, protein, and enzyme activity was specific and resulted in >95% inhibition of protein formation. In conclusion, in this article we provide a protocol for an optimized AS-mediated knockdown, representing a specific and efficient instrument for blocking of iNOS formation and allowing for studying the impact of iNOS expression on endothelial function. We also expose application problems of this technique when working in inflammatory conditions.

scholarly journals Immunomodulatory Activity of a Traditional Sri Lankan Concoction of Coriandrum sativum L. and Coscinium fenestratum G.

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Shashika Dinethri Kothalawala ◽  
Daniya Edward ◽  
Jayamini C. Harasgama ◽  
Loshini Ranaweera ◽  
Ovitigala Vithanage Don Sisira Jagathpriya Weerasena ◽  
...  
Keyword(s):  
Significant Inhibition ◽  
Inos Expression ◽  
Inflammatory Activity ◽  
Immunomodulatory Activity ◽  
No Production ◽  
Sri Lankan ◽  
Paw Edema ◽  
Peritoneal Cells ◽  
Anti Inflammatory

Objective. To investigate the immunomodulatory activity of a traditional Sri Lankan concoction of Coriandrum sativum L. and Coscinium fenestratum (Gaertn.) Colebr., which is a Sri Lankan traditional medicine used to relieve inflammation and cold. Methods. In vivo anti-inflammatory activity was tested using carrageenan-induced rat paw-edema model. Mechanism of anti-inflammatory activity was assessed by investigating the production of nitric oxide (NO), expression of iNOS enzyme, and reactive oxygen species (ROS) by rat peritoneal cells. The membrane stabilizing activity was also tested. The antibody response was determined by assessing the specific haemagglutination antibodies raised against sheep red blood cells. Results. The three doses of freeze-dried concoction used ((human equivalent dose (HED)—183 mg/kg) 2 × HED and 1/2HED; n = 6 rats/group) showed significant inhibition of paw edema compared to water control at 3rd–5th hours (p<0.05). Both HED and 1/2HED exhibited marked anti-inflammatory activity (72–83% inhibition at 4th-5th hours; p<0.05). The HED of the concoction showed significant inhibition of NO (77.5 ± 0.73%, p<0.001) and ROS production (26.9 ± 2.55%; p<0.01) by rat peritoneal cells. Inhibition of NO production in the concoction treated rat peritoneal cells was confirmed by the lack of iNOS expression. The concoction also exhibited significant membrane stabilizing activity (IC50 = 0.0006 μg/ml; p=0.001). HED resulted in a significantly high induction of specific antibody production against SRBC antigens as detected by SRBC haemagglutination assay (mean day 14 titers 253.3 compared to control: 66.7) (p<0.01). Conclusions. The traditional Sri Lankan concoction of C. sativum and C. fenestratum demonstrated potent in vivo anti-inflammatory activity, significant reduction of ROS, and NO production by rat peritoneal cells and the lack of iNOS expression confirmed the low NO production. The increased membrane stability also supports the anti-inflammatory activity of the concoction. Further, this concoction induced a significantly high antibody response reflecting its immunostimulatory activity. Together these results scientifically validate the therapeutic use of the concoction of C. sativum and C. fenestratum in Sri Lankan traditional medicinal system for immunomodulatory effects.

scholarly journals microRNA-146a promotes mycobacterial survival in macrophages through suppressing nitric oxide production

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Miao Li ◽  
Jinli Wang ◽  
Yimin Fang ◽  
Sitang Gong ◽  
Meiyu Li ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Mycobacterial Infection ◽  
Nuclear Factor Κb ◽  
Inos Expression ◽  
Transcriptional Level ◽  
No Production ◽  
Promising Therapeutic Target ◽  
Mitogen Activated Protein

Abstract Macrophages play a crucial role in host innate anti-mycobacterial defense, which is tightly regulated by multiple factors, including microRNAs. Our previous study showed that a panel of microRNAs was markedly up-regulated in macrophages upon mycobacterial infection. Here, we investigated the biological function of miR-146a during mycobacterial infection. miR-146a expression was induced both in vitro and in vivo after Mycobacterium bovis BCG infection. The inducible miR-146a could suppress the inducible nitric oxide (NO) synthase (iNOS) expression and NO generation, thus promoting mycobacterial survival in macrophages. Inhibition of endogenous miR-146a increased NO production and mycobacterial clearance. Moreover, miR-146a attenuated the activation of nuclear factor κB and mitogen-activated protein kinases signaling pathways during BCG infection, which in turn repressed iNOS expression. Mechanistically, miR-146a directly targeted tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) at post-transcriptional level. Silencing TRAF6 decreased iNOS expression and NO production in BCG-infected macrophages, while overexpression of TRAF6 reversed miR-146a-mediated inhibition of NO production and clearance of mycobacteria. Therefore, we demonstrated a novel role of miR-146a in the modulation of host defense against mycobacterial infection by repressing NO production via targeting TRAF6, which may provide a promising therapeutic target for tuberculosis.

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