scholarly journals Down-regulation of NF-κB signalling by polyphenolic compounds prevents endotoxin-induced liver injury in a rat model

2011 ◽  
Vol 18 (1) ◽  
pp. 70-79 ◽  
Author(s):  
Sushma Bharrhan ◽  
Kanwaljit Chopra ◽  
Sunil K Arora ◽  
Jaideep S Toor ◽  
Praveen Rishi
Keyword(s):  
Liver Injury ◽  
Therapeutic Agent ◽  
Polyphenolic Compounds ◽  
Oxygen Species ◽  
Enhanced Production ◽  
Signalling Molecule ◽  
Tnf Α ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide ◽  
Pharmacological Basis

Activation of NF-κB has been reported to play a key role in causing endotoxin-induced hepatic damage through enhanced production of reactive oxygen species and pro-inflammatory mediators. In this context, the potential of polyphenolic phytochemicals in preventing endotoxin-induced liver damage remains unclear. Here, we demonstrate that catechin and quercetin have the potential to down-regulate the initial signalling molecule NF-κB which may further inhibit the downstream cascade including TNF-α and NO. These results were confirmed using N-nitro-L-arginine methyl ester (L-NAME), the inhibitor of inducible nitric oxide synthase (iNOS) along with the biochemical and histological alterations occurring in the presence and absence of supplementation with both the polyphenols. However, catechin was found to be more effective than quercetin against endotoxin-induced liver injury. These findings suggest that these polyphenols may form a pharmacological basis for designing a therapeutic agent against endotoxin-mediated oxidative damage.

scholarly journals Curcumin protects liver inflammation by suppressing expression of inducible nitric oxide synthase in primary cultured rat hepatocytes

2017 ◽  
Vol 7 (9) ◽  
pp. 716 ◽  
Author(s):  
Richi Nakatake ◽  
Hidehiko Hishikawa ◽  
Hideyuki Matushima ◽  
Yusuke Nakamura ◽  
Morihiko Ishizaki ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Liver Injury ◽  
Rat Hepatocytes ◽  
No Production ◽  
Type I ◽  
Tnf Α ◽  
Cultured Rat Hepatocytes ◽  
Oxide Synthase ◽  
Necrosis Factor ◽  
Inducible Nitric Oxide

Background: Curcumin has beneficial effects on organ metabolism. However, there is little evidence that curcumin affects inflammatory mediators, such as tumor necrosis factor (TNF)-α and nitric oxide (NO). In an inflamed liver, proinflammatory cytokines stimulate liver cells, followed by the induction of inducible NO synthase (iNOS). Excessive NO produced by iNOS is one of the factors in liver injury. Therefore, inhibiting iNOS induction for preventing liver injury is important.Objective: This study aimed to investigate liver protective effects of curcumin by examining interleukin (IL)-1β-stimulated hepatocytes.Methods: Primary cultured rat hepatocytes were treated with IL-1β in the presence or absence of curcumin. Induction of NO production and iNOS, and the signaling pathway of iNOS were analyzed.Results: Simultaneous addition of IL-1β and curcumin decreased expression levels of iNOS protein and mRNA, resulting in inhibition of NO production. Curcumin also reduced mRNA expression of TNF-α and IL-6. Curcumin inhibited two essential signaling pathways for iNOS induction, NF-κB activation and type I IL-1 receptor upregulation. Transfection experiments revealed that curcumin reduced iNOS mRNA levels at the promoter activation and mRNA stabilization steps. Delayed administration of curcumin after IL-1β addition also inhibited iNOS induction.Conclusions: Curcumin affects induction of inflammatory mediators, such as iNOS and TNF-α, in part through the inhibition of NF-κB activation in hepatocytes. Curcumin may have therapeutic potential for organ injuries, including the liver.Key words: curcumin, inducible nitric oxide synthase, liver injury, primary cultured hepatocytes, nuclear factor-κB, type I interleukin-1 receptor, tumor necrosis factor-α. 

scholarly journals Glutathione inhibits expression of the proinflammatory biomarker inducible nitric oxide synthase in hepatocytes

2018 ◽  
Vol 8 (12) ◽  
pp. 544
Author(s):  
Richi Nakatake ◽  
Masaya Kotsuka ◽  
Yuki Hashimoto ◽  
Masahiko Hatta ◽  
Morihiko Ishizaki ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Liver Injury ◽  
Inducible Nitric Oxide Synthase ◽  
Type I ◽  
Tnf Α ◽  
Oxide Synthase ◽  
Necrosis Factor ◽  
Inducible Nitric Oxide ◽  
Inos Induction

Background: Intracellular glutathione (GSH) plays an important regulatory role in the host response to liver injury. However, there have been few scientific reports on the anti-inflammatory effects of GSH. In the inflamed liver, proinflammatory cytokines stimulate liver cells, followed by expression of inducible nitric oxide synthase (iNOS). Excessive nitric oxide (NO) levels produced by iNOS are one of the factors involved in liver injury. Therefore, inhibiting iNOS induction is important for preventing liver injury. This study aimed to investigate the protective effects of GSH on the liver by examining interleukin (IL)-1β-stimulated hepatocytes.Methods: Primary cultured rat hepatocytes were treated with IL-1β in the presence or absence of GSH. Induction of iNOS and its signaling pathway were analyzed.Results: Addition of GSH decreased IL-1β-induced iNOS protein and mRNA expression levels, which resulted in inhibition of NO production. GSH also decreased tumor necrosis factor (TNF)-α and IL-6 mRNA expression. GSH blocked “type I IL-1 receptor upregulation”, one of the essential signaling pathways for iNOS induction, through inactivation of an upstream kinase, phosphatidylinositol 3-kinase/Akt. In contrast, GSH had no effects on degradation of IκB and activation of NF-ĸB (nuclear translocation and its DNA binding). Transfection experiments revealed that GSH reduced iNOS mRNA levels at the promoter transactivation and mRNA stabilization steps. Delayed administration of GSH after IL-1β addition also inhibited iNOS induction. Conclusions: Our study suggests that GSH affects induction of inflammatory mediators, including iNOS and TNF-α, indicating its therapeutic potential for organ injuries, especially for the liver.Keywords: glutathione, inducible nitric oxide synthase, liver injury, primary cultured hepatocytes, type I interleukin-1 receptor, tumor necrosis factor-α

scholarly journals Protective effects of active hexose correlated compound in a rat model of liver injury after hepatectomy

2016 ◽  
Vol 6 (11) ◽  
pp. 702 ◽  
Author(s):  
Richi Nakatake ◽  
Yoshito Tanaka ◽  
Yosuke Ueyama ◽  
Hirokazu Miki ◽  
Morihiko Ishizaki ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Liver Injury ◽  
Rat Model ◽  
Inflammatory Mediators ◽  
Nuclear Factor ◽  
Protective Effects ◽  
Tnf Α ◽  
Oxide Synthase ◽  
Necrosis Factor ◽  
Inducible Nitric Oxide

Background: Recent evidence has indicated that a functional food, active hexose correlated compound (AHCC), has liver-protective effects via suppression of inflammatory mediators, such as inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-α.Objective: This study aimed to investigate whether AHCC has beneficial effects in a rat model of endotoxin-induced liver injury after partial hepatectomy, in addition to clarifying the mechanisms of action of AHCC.Methods: Rats were treated with 70% of partial hepatectomy and lipopolysaccharide (PH/LPS) to induce acute liver injury. A normal diet with or without 2% AHCC was administered orally 10 days before 70% hepatectomy. Inflammatory mediators were analyzed.Results: AHCC improved the survival rate by 70% in PH/LPS rats. AHCC prevented an increase in serum transaminase levels, and histopathological changes and apoptosis in the liver. AHCC reduced iNOS mRNA and protein expression in the liver, resulting in inhibition of nitric oxide production. AHCC also reduced TNF-α, cytokine-induced neutrophil chemoattractant-1, and interleukin-6 mRNA expression, but enhanced expression of interleukin-10. An electrophoretic mobility shift assay with hepatic nuclear extracts demonstrated that AHCC reduced the activation of nuclear factor (NF)-κB induced by PH/LPS treatment.Conclusion: AHCC inhibits induction of inflammatory mediators, including iNOS and TNF-α, in part through inhibition of NF-κB activation in a rat model of liver injury. Our findings suggest that AHCC prevents postoperative liver failure after liver resection.Keywords: active hexose correlated compound, inducible nitric oxide synthase, liver injury, nuclear factor-κB, tumor necrosis factor-α

Suppressive effects of sulfated polysaccharide ascophyllan isolated from Ascophyllum nodosum on the production of NO and ROS in LPS-stimulated RAW264.7 cells

2020 ◽  
Vol 85 (4) ◽  
pp. 882-889
Author(s):  
Yan Liang ◽  
Shijiao Zha ◽  
Masanobu Tentaku ◽  
Takasi Okimura ◽  
Zedong Jiang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Ascophyllum Nodosum ◽  
Sulfated Polysaccharide ◽  
Intracellular Reactive Oxygen Species ◽  
Raw264.7 Cells ◽  
Dependent Manner ◽  
Oxygen Species ◽  
Oxide Synthase ◽  
Dose Dependent ◽  
Inducible Nitric Oxide

ABSTRACT In this study, we found that a sulfated polysaccharide isolated from the brown alga Ascophyllum nodosum, ascophyllan, showed suppressive effects on stimulated RAW264.7 cells. Ascophyllan significantly inhibited expression of inducible nitric oxide synthase mRNA and excessive production of nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated RAW264.7 cells in a dose-dependent manner without affecting the viability of RAW264.7 cells. Ascophyllan also reduced the elevated level of intracellular reactive oxygen species (ROS) in LPS-stimulated RAW264.7 cells. Furthermore, preincubation with ascophyllan resulted in concentration-dependent decrease in ROS production in phorbol 12-myristate-13-acetate-stimulated RAW264.7 cells. Our results suggest that ascophyllan can exhibit anti-inflammatory effects on stimulated macrophages mainly through the attenuation of NO and ROS productions.

Abstract 316: Effects of Inhibiting of Inducible Nitric Oxide Synthase in the Pathophysiology of Experimental Preeclampsia

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Lorena M Amaral ◽  
Ana Carolina T Palei ◽  
Lucas C Pinheiro ◽  
Jonas T Sertorio ◽  
Danielle A Guimaraes ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Inducible Nitric Oxide Synthase ◽  
Inos Expression ◽  
Oxygen Species ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

The pathophysiology of preeclampsia (PE) is not entirely known. However, increased oxidative stress possibly leading to impaired nitric oxide activity has been implicated in the critical condition. Increased oxidative stress with increased levels of highly reactive species including superoxide may generate peroxynitrite. We examined the role of inducible nitric oxide synthase (iNOS) and oxidative stress in the reduced uterine perfusion pressure (RUPP) preeclampsia experimental model. METHODS: RUPP was induced in wistar rats. Pregnant rats in the RUPP group had their aortic artery clipped at day 14 of gestation. After a midline incision, a silver clip (0.203 mm) was placed around the aorta above the iliac bifurcation; silver clips (0.100 mm) were also placed on branches of both the right and left ovarian arteries that supply the uterus. Sham-operated (pregnant control rats) and RUPP rats were treated with oral vehicle or 1 mg/kg/day 1400W (iNOS inhibitor) for 5 days. Mean arterial pressure (MAP) and plasma levels of thiobarbituric acid-reactive species (TBARS) and total radical-trapping antioxidant potential (TRAP) were measured determined. Aortic iNOS expression (Western blotting) and reactive oxygen species (ROS; assessed by fluorescence microscopy with dihydroethidium-DHE) were measured. We found increased mean arterial pressure in RUPP compared with pregnant control rats (MAP= 128±1 vs. 100±1.8 mmHg, respectively; P<0.05) and 1400W exerted antihypertensive effects (MAP= 114±2 vs.128±1 mmHg in RUPP treated and untreated rats, respectively; P<0.05). Higher reactive oxygen species (ROS) concentrations were found in RUPP compared with pregnant control rats (7.1±0.5 vs. 5.1±0.5 arbitrary units (A.U.), respectively; P<0.05) and 1400W decreased ROS production to 5.8±0.02 A.U. in RUPP treated rats, P<0.05. In addition, 1400W attenuated iNOS expression in RUPP rats (0.29±0.02 vs. 0.55±0.8 A.U. in RUPP treated and untreated rats, respectively; P<0.01) and had no effects on plasma TBARS and TRAP levels. Our results suggest that 1400w exerts antihypertensive effects in the RUPP model and suppresses ROS formation. Supported by FAPESP,Cnpq.

scholarly journals Aminoguanidine Protects Boar Spermatozoa against the Deleterious Effects of Oxidative Stress

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 212 ◽  
Author(s):  
Eliana Pintus ◽  
Martin Kadlec ◽  
Marija Jovičić ◽  
Markéta Sedmíková ◽  
José Ros-Santaella
Keyword(s):  
Oxidative Stress ◽  
Therapeutic Agent ◽  
Antioxidant Properties ◽  
In Vitro Effects ◽  
Oxide Synthase ◽  
Boar Spermatozoa ◽  
Generating System ◽  
Control Samples ◽  
Inducible Nitric Oxide

Aminoguanidine is a selective inhibitor of the inducible nitric oxide synthase (iNOS) and a scavenger of reactive oxygen species (ROS). Numerous studies have shown the antioxidant properties of aminoguanidine in several cell lines, but the in vitro effects of this compound on spermatozoa under oxidative stress are unknown. In this study, we tested the hypothesis that aminoguanidine may protect against the detrimental effects of oxidative stress in boar spermatozoa. For this purpose, sperm samples were incubated with a ROS generating system (Fe2+/ascorbate) with or without aminoguanidine supplementation (10, 1, and 0.1 mM). Our results show that aminoguanidine has powerful antioxidant capacity and protects boar spermatozoa against the deleterious effects of oxidative stress. After 2 h and 3.5 h of sperm incubation, the samples treated with aminoguanidine showed a significant increase in sperm velocity, plasma membrane and acrosome integrity together with a reduced lipid peroxidation in comparison with control samples (p < 0.001). Interestingly, except for the levels of malondialdehyde, the samples treated with 1 mM aminoguanidine did not differ or showed better performance than control samples without Fe2+/ascorbate. The results from this study provide new insights into the application of aminoguanidine as an in vitro therapeutic agent against the detrimental effects of oxidative stress in semen samples.

scholarly journals Protection against acetaminophen-induced liver injury and lethality by interleukin 10: Role of inducible nitric oxide synthase

Hepatology ◽  
2002 ◽  
Vol 35 (2) ◽  
pp. 289-298 ◽  
Author(s):  
Mohammed Bourdi ◽  
Yasuhiro Masubuchi ◽  
Timothy P. Reilly ◽  
Hamid R. Amouzadeh ◽  
Jackie L. Martin ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Liver Injury ◽  
Inducible Nitric Oxide Synthase ◽  
Interleukin 10 ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide
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