scholarly journals Glycyrrhizic Acid Attenuates Sepsis-Induced Acute Kidney Injury by Inhibiting NF-κB Signaling Pathway

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Hongyu Zhao ◽  
Min Zhao ◽  
Yu Wang ◽  
Fengchun Li ◽  
Zhigang Zhang
Keyword(s):  
Nitric Oxide ◽  
Acute Kidney Injury ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Glycyrrhizic Acid ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Serum Samples ◽  
Oxide Synthase ◽  
Caecal Ligation And Puncture

Glycyrrhizic acid (GA) is a major active ingredient in licorice. In our study, the effects of GA on acute kidney injury (AKI) in rats and its underlying molecular mechanisms were investigated. The sepsis model was produced by caecal ligation and puncture (CLP) in rats. The molecular and histological experiments were performed in the kidney tissues and serum samples of rats. According to the results obtained, GA alleviated sepsis-induced AKI by improving the pathological changes, decreasing the levels of blood urea nitrogen (BUN), creatinine (Cre), and increasing the survival rate of rats with AKI significantly. The production of inflammatory cytokines, such as TNF-α, IL-1β, and IL-6, was markedly inhibited by GA. Moreover, treatment with GA inhibited the production of nitric oxide (NO) and prostaglandin E2 (PGE2) and expression levels of induced nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in kidney tissues. Furtherly, the apoptosis in kidney tissue induced by AKI was suppressed by GA. Finally, GA could inhibit the activation of NF-κB signaling pathway. Our study suggests that GA alleviates sepsis-induced AKI by inhibiting the NF-κB signaling pathway, which provides a strong evidence for a new approach for treating sepsis-induced AKI.

DDAH-2 alleviates contrast medium iopromide-induced acute kidney injury through nitric oxide synthase

2019 ◽  
Vol 133 (23) ◽  
pp. 2361-2378 ◽  
Author(s):  
Heng-Huei Lin ◽  
Tzong-Shyuan Lee ◽  
Shing-Jong Lin ◽  
Yi-Chen Yeh ◽  
Tse-Min Lu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Acute Kidney Injury ◽  
Nitric Oxide Synthase ◽  
Protective Effect ◽  
Contrast Medium ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Ros Generation ◽  
Oxide Synthase

Abstract Background: Contrast medium-induced acute kidney injury (CI-AKI) is one of the most common causes of hospital-acquired acute renal failure. However, the pathogenesis of CI-AKI remains unclear. Asymmetric dimethylarginine (ADMA) is an endogenous nitric oxide synthase (NOS) inhibitor that is largely metabolised by dimethylarginine dimethylaminohydroxylase (DDAH) in humans. Two isoforms of DDAH exist, namely, DDAH-1 and DDAH-2. In the present study, we examined whether the DDAH-2/ADMA/NOS pathway is involved in the pathogenesis of CI-AKI. Methods and Results: Exposure to the contrast medium iopromide led to increase in creatinine and blood urea nitrogen (BUN) levels, accumulation of ADMA, increase in reactive oxygen species (ROS) generation, and an inflammatory response in mice kidney tissue. The injection of adenovirus-harbouring DDAH-2 lowered renal ADMA levels and had a reno-protective effect against contrast-medium injury by decreasing cell apoptosis, ROS, and fibrosis. By contrast, contrast medium-induced renal injury was exacerbated in heterozygous DDAH-2 knockout mice. In the in vitro study, overexpression of DDAH-2 increased the levels of nitrite and intracellular cGMP, while the DDAH-2 knockdown induced the opposite effect. These findings were also observed in the in vivo sample. Conclusions: Our findings provide the first evidence that the DDAH-2/ADMA/NOS pathway is involved in the pathogenesis of CI-AKI and that the protective effect of DDAH-2 probably arises from the modulation of NOS activity, oxidative stress, and the inflammatory process.

scholarly journals Identification of novel metabolomic biomarkers in an experimental model of septic acute kidney injury

2019 ◽  
Vol 316 (1) ◽  
pp. F54-F62 ◽  
Author(s):  
Jose L. Izquierdo-Garcia ◽  
Nicolás Nin ◽  
Pablo Cardinal-Fernandez ◽  
Yenny Rojas ◽  
Marta de Paula ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Blood Flow ◽  
Arterial Pressure ◽  
Experimental Model ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Principal Component ◽  
Renal Tissue ◽  
Serum Samples ◽  
Neutrophil Gelatinase Associated Lipocalin

The aim of this study is the identification of metabolomic biomarkers of sepsis and sepsis-induced acute kidney injury (AKI) in an experimental model. Pigs were anesthetized and monitored to measure mean arterial pressure (MAP), systemic blood flow (QT), mean pulmonary arterial pressure, renal artery blood flow (QRA), renal cortical blood flow (QRC), and urine output (UO). Sepsis was induced at t = 0 min by the administration of live Escherichia coli ( n = 6) or saline ( n = 8). At t = 300 min, animals were killed. Renal tissue, urine, and serum samples were analyzed by nuclear magnetic resonance (NMR) spectroscopy. Principal component analyses were performed on the processed NMR spectra to highlight kidney injury biomarkers. Sepsis was associated with decreased QT and MAP and decreased QRA, QRC, and UO. Creatinine serum concentration and neutrophil gelatinase-associated lipocalin (NGAL) serum and urine concentrations increased. NMR-based metabolomics analysis found metabolic differences between control and septic animals: 1) in kidney tissue, increased lactate and nicotinuric acid and decreased valine, aspartate, glucose, and threonine; 2) in urine, increased isovaleroglycine, aminoadipic acid, N-acetylglutamine, N-acetylaspartate, and ascorbic acid and decreased myoinositol and phenylacetylglycine; and 3) in serum, increased lactate, alanine, pyruvate, and glutamine and decreased valine, glucose, and betaine concentrations. The concentration of several metabolites altered in renal tissue and urine samples from septic animals showed a significant correlation with markers of AKI (i.e., creatinine and NGAL serum concentrations). NMR-based metabolomics is a potentially useful tool for biomarker identification of sepsis-induced AKI.

DDAH-2 Alleviates Contrast Medium Iopromide-Induced Acute Kidney Injury Through Nitric Oxide Synthase

2019 ◽  
Author(s):  
Heng-Huei Lin ◽  
Tzong-Shyuan Lee ◽  
Shing-Jong Lin ◽  
Yi-Chen Yeh ◽  
Tse-Min Lu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Acute Kidney Injury ◽  
Nitric Oxide Synthase ◽  
Contrast Medium ◽  
Kidney Injury ◽  
Oxide Synthase

Erythropoietin prevents sepsis-related acute kidney injury in rats by inhibiting NF-κB and upregulating endothelial nitric oxide synthase

2012 ◽  
Vol 302 (8) ◽  
pp. F1045-F1054 ◽  
Author(s):  
Ana Carolina C. Pessoa de Souza ◽  
Rildo A. Volpini ◽  
Maria Heloísa Shimizu ◽  
Talita Rojas Sanches ◽  
Niels Olsen Saraiva Camara ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Acute Kidney Injury ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
Inulin Clearance ◽  
Enos Expression ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

The pathophysiology of sepsis involves complex cytokine and inflammatory mediator networks, a mechanism to which NF-κB activation is central. Downregulation of endothelial nitric oxide synthase (eNOS) contributes to sepsis-induced endothelial dysfunction. Erythropoietin (EPO) has emerged as a major tissue-protective cytokine in the setting of stress. We investigated the role of EPO in sepsis-related acute kidney injury using a cecal ligation and puncture (CLP) model. Wistar rats were divided into three primary groups: control (sham-operated); CLP; and CLP+EPO. EPO (4,000 IU/kg body wt ip) was administered 24 and 1 h before CLP. Another group of rats received N-nitro-l-arginine methyl ester (l-NAME) simultaneously with EPO administration (CLP+EPO+l-NAME). A fifth group (CLP+EPOtreat) received EPO at 1 and 4 h after CLP. At 48 h postprocedure, CLP+EPO rats presented significantly higher inulin clearance than did CLP and CLP+EPO+l-NAME rats; hematocrit levels, mean arterial pressure, and metabolic balance remained unchanged in the CLP+EPO rats; and inulin clearance was significantly higher in CLP+EPOtreat rats than in CLP rats. At 48 h after CLP, creatinine clearance was significantly higher in the CLP+EPO rats than in the CLP rats. In renal tissue, pre-CLP EPO administration prevented the sepsis-induced increase in macrophage infiltration, as well as preserving eNOS expression, EPO receptor (EpoR) expression, IKK-α activation, NF-κB activation, and inflammatory cytokine levels, thereby increasing survival. We conclude that this protection, which appears to be dependent on EpoR activation and on eNOS expression, is attributable, in part, to inhibition of the inflammatory response via NF-κB downregulation.

The Signaling Pathways in Nitric Oxide Production by Neutrophils Exposed to N-nitrosodimethylamine

2018 ◽  
Vol 16 (2) ◽  
pp. 194-199
Author(s):  
Wioletta Ratajczak-Wrona ◽  
Ewa Jablonska
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Polymorphonuclear Neutrophils ◽  
Microbial Pathogens ◽  
Human Neutrophils ◽  
No Production ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Background: Polymorphonuclear neutrophils (PMNs) play a crucial role in the innate immune system’s response to microbial pathogens through the release of reactive nitrogen species, including Nitric Oxide (NO). </P><P> Methods: In neutrophils, NO is produced by the inducible Nitric Oxide Synthase (iNOS), which is regulated by various signaling pathways and transcription factors. N-nitrosodimethylamine (NDMA), a potential human carcinogen, affects immune cells. NDMA plays a major part in the growing incidence of cancers. Thanks to the increasing knowledge on the toxicological role of NDMA, the environmental factors that condition the exposure to this compound, especially its precursors- nitrates arouse wide concern. Results: In this article, we present a detailed summary of the molecular mechanisms of NDMA’s effect on the iNOS-dependent NO production in human neutrophils. Conclusion: This research contributes to a more complete understanding of the mechanisms that explain the changes that occur during nonspecific cellular responses to NDMA toxicity.

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