scholarly journals Maresin 1 Attenuates Lipopolysaccharide-Induced Acute Kidney Injury via Inhibiting NOX4/ROS/NF-κB Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiameng Li ◽  
Zhuyun Zhang ◽  
Liya Wang ◽  
Luojia Jiang ◽  
Zheng Qin ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Signaling Pathway ◽  
Kidney Injury ◽  
Lipid Mediator ◽  
Tubular Damage ◽  
Omega 3 ◽  
Nitrogen Levels ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Maresin 1

Sepsis-associated acute kidney injury (S-AKI) is a common complication in hospitalized and critically ill patients, which increases the risk of multiple comorbidities and is associated with extremely high mortality. Maresin 1 (MaR1), a lipid mediator derived from the omega-3 fatty acid docosahexaenoic acid has been reported to protect against inflammation and promote the regression of acute inflammation. This study proposed to systematically investigate the renoprotective effects and potential molecular mechanism of MaR1 in septic acute kidney injury. We established a S-AKI animal model by a single intraperitoneal injection of lipopolysaccharide (LPS), 10 mg/kg, on male C57BL/6J mice. LPS-stimulated (100 μg/ml) mouse kidney tubular epithelium cells (TCMK-1) were used to simulate septic AKI in vitro. The results showed that pretreatment with MaR1 significantly reduced serum creatinine and blood urea nitrogen levels as well as tubular damage scores and injury marker neutrophil gelatinase-associated lipocalin in septic AKI mice. Meanwhile, MaR1 administration obviously diminished pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, and MCP-1), downregulated BAX and cleaved caspase-3 expression, and upregulated BCL-2 expression in the injured kidney tissues and TCMK-1 cells. In addition, MaR1 reduced malondialdehyde production and improved the superoxide dismutase activity of renal tissues while inhibiting reactive oxygen species (ROS) production and protecting the mitochondria. Mechanistically, LPS stimulated the expression of the NOX4/ROS/NF-κB p65 signaling pathway in S-AKI kidneys, while MaR1 effectively suppressed the activation of the corresponding pathway. In conclusion, MaR1 attenuated kidney inflammation, apoptosis, oxidative stress, and mitochondrial dysfunction to protect against LPS-induced septic AKI via inhibiting the NOX4/ROS/NF-κB p65 signaling pathway.

scholarly journals Relaxin Attenuates Contrast-Induced Human Proximal Tubular Epithelial Cell Apoptosis by Activation of the PI3K/Akt Signaling Pathway In Vitro

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Xiang-Cheng Xie ◽  
Yizhi Cao ◽  
Xiu Yang ◽  
Qun-Hong Xu ◽  
Wei Wei ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Kidney Injury ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Bax Protein ◽  
Phosphorylated Akt

Background. Contrast-induced acute kidney injury (CI-AKI) is one of the main causes of iatrogenic acute kidney injury (AKI); however, therapeutic strategies for AKI remain limited. This study aims to explore the effect of relaxin (RLX) on contrast-induced HK-2 apoptosis and its underlying mechanisms.Methods. Renal tubular epithelial cells (HK-2) were incubated either with or without ioversol, human H2 relaxin, and LY294002 (the inhibitor of the PI3K/Akt signal pathway). Cell viability was evaluated with a CCK-8 assay. Apoptotic morphologic alterations were observed using the Hoechst 33342 staining method. Apoptosis was detected with Annexin V staining. Western blot analysis was employed to measure the expression of pAkt (S473), Akt, cleaved caspase-3, Bcl-2, Bax, and actin proteins.Results. Ioversol reduced the viability of HK-2 cells. Western blotting results revealed decreased expression of phosphorylated Akt in cells treated with ioversol. The activities of caspase-3 and Bax protein increased, while the expression of Bcl-2 protein decreased. As a result, the Bax/Bcl-2 ratio increased after treatment with ioversol. These effects were reversed when HK-2 cells were cotreated with RLX. However, with preadministration of PI3K/Akt pathway inhibitor LY294002, the effect of RLX was blocked.Conclusion. Our study demonstrates that relaxin attenuates ioversol induced cell apoptosis via activation of the PI3K/Akt signaling pathway, suggesting that RLX might play a protective role in the treatment of CI-AKI.

scholarly journals Obeticholic acid ameliorates hepatorenal syndrome in ascitic cirrhotic rats by down-regulating the renal 8-iso-PGF2α-activated COX-TXA2 pathway

2020 ◽  
Vol 134 (15) ◽  
pp. 2055-2073
Author(s):  
Yu-Lien Tsai ◽  
Chih-Wei Liu ◽  
Chien-Fu Hsu ◽  
Chia-Chang Huang ◽  
Ming-Wei Lin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hepatorenal Syndrome ◽  
Rat Kidney ◽  
Kidney Injury ◽  
Tubular Damage ◽  
Obeticholic Acid ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Duct Ligation ◽  
Renal Tubular

Abstract Backgrounds/Aims: The present study explores the potential of chronic treatment with the Foresaid X receptor (FXR) agonist obeticholic acid (OCA), which inhibits oxidative stress-related pathogenesis, in ascitic cirrhotic rats with hepatorenal syndrome (HRS) developed 6 weeks after bile duct ligation (BDL). Methods: Systemic, splanchnic, and renal hemodynamics and pathogenic cascades were measured in ascitic BDL and sham rats receiving 2-weeks of either vehicle or OCA treatments (sham-OCA and BDL-OCA groups), and NRK-52E cells, rat kidney tubular epithelial cells. Results: Chronic OCA treatment significantly normalized portal hypertension, glomerular filtration rate, urine output, renal blood flow; decreased ascites, renal vascular resistance, serum creatinine, and the release of renal tubular damage markers, including urinary neutrophil gelatinase-associated lipocalin (uNGAL) and kidney injury moleculae-1 (uKim-1) in BDL-OCA rats. In the BDL group, inhibition of the renal oxidative stress (8-iso-PGF2α)-activated cyclooxygenase-thromboxane A2 [COX-TXA2] pathway, apoptosis, and tubular injury accompanied by a decrease in hyper-responsiveness to the vasoconstrictor 8-iso-PGF2α in perfused kidneys. In vitro experiments revealed that 8-iso-PGF2α induced oxidative stress, release of reactive oxygen species, and cell apoptosis, which were reversed by concomitant incubation with the FXR agonist. Conclusions: Through the inhibition of renal 8-iso-PGF2α production and the down-regulation of the COX-TXA2 pathway, our study suggests that chronic OCA treatment can ameliorate the HRS in ascitic cirrhotic rats. Thus, OCA is an agent with antioxidative stress, antivasoconstrictive, antiapoptotic properties which benefit ascitic, cirrhotic rats with systemic, hepatic, and renal abnormalities.

Neutrophil Gelatinase-Associated Lipocalin for the Early Prediction of Acute Kidney Injury in ST-Segment Elevation Myocardial Infarction Patients Treated with Primary Percutaneous Coronary Intervention

2020 ◽  
Vol 10 (3) ◽  
pp. 154-161
Author(s):  
Ilan Merdler ◽  
Keren-Lee Rozenfeld ◽  
David Zahler ◽  
Moshe Shtark ◽  
Ilana Goldiner ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Kidney Injury ◽  
Sensitivity And Specificity ◽  
Kidney Injury ◽  
Coronary Intervention ◽  
Tubular Damage ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Plasma Ngal ◽  
Renal Tubular ◽  
Neutrophil Gelatinase

Introduction and Objective: Neutrophil gelatinase-associated lipocalin (NGAL), a glycoprotein released by renal tubular cells, can be used as a marker of early tubular damage. We evaluated plasma NGAL level utilization for the identification of acute kidney injury (AKI) among ST-elevation myocardial infarction (STEMI) patients undergoing primary coronary intervention (PCI). Methods: 131 STEMI patients treated with PCI were prospectively included. Plasma NGAL levels were drawn prior to PCI (0 h) and 24 h afterwards. AKI was defined per KDIGO criteria of serum creatinine increase. Receiver-operating characteristic (ROC) methods were used to identify optimal sensitivity and specificity for the observed NGAL range. Results: Overall AKI incidence was 14%. NGAL levels were significantly higher for patients with AKI at both 0 h (164 ± 42 vs. 95 ± 30; p < 0.001) and 24 h (142 ± 41 vs. 93 ± 36; p < 0.001). Per ROC curve analysis, an optimal cutoff value of NGAL (>120 ng/mL) predicted AKI with 80% sensitivity and specificity (AUC 0.881, 95%, CI 0.801–0.961, p < 0.001). In a multivariate logistic regression model, NGAL levels were independently associated with AKI at 0 h (OR 1.044, 95% CI 1.013–1.076; p = 0.005) and 24 h (OR 1.018, 95% CI 1.001–1.036; p = 0.04). Conclusions: Elevated NGAL levels, suggesting renal tubular damage, are independently associated with AKI in STEMI patients undergoing primary PCI.

Acute kidney injury and renal tubular damage in children with type 1 diabetes mellitus onset

2021 ◽  
Author(s):  
Pierluigi Marzuillo ◽  
Dario Iafusco ◽  
Angela Zanfardino ◽  
Stefano Guarino ◽  
Alessia Piscopo ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Biochemical Parameters ◽  
Kidney Injury ◽  
Fractional Excretion ◽  
Tubular Damage ◽  
Renal Tubular Damage ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Renal Tubular ◽  
Beta 2 Microglobulin ◽  
Physiological And Biochemical

Abstract Context Acute kidney injury(AKI) and renal tubular damage(RTD), especially if complicated by acute tubular necrosis (ATN), could increase the risk of later chronic kidney disease. No prospective studies on AKI and RTD in children with type1diabetes mellitus(T1DM) onset are available. Objectives to evaluate the AKI and RTD prevalence, and their rate and timing of recovery in children with T1DM onset. Design prospective study. Settings and patients: 185children were followed up after 14days from T1DM onset. The patients who did not recover from AKI/RTD were followed-up 30 and 60days later. Main outcome measures AKI was defined according to the KDIGO criteria. RTD was defined by abnormal urinary beta-2-microglobulin and/or neutrophil gelatinase-associated lipocalin and/or tubular reabsorption of phosphate&lt;85% and/or fractional excretion of Na(FENa)&gt;2%. ATN was defined by RTD+AKI, prerenal-(P-)AKI by AKI+FENa&lt;1% while acute tubular damage(ATD) by RTD without AKI. Results Prevalence of diabetic ketoacidosis(DKA) and AKI were 51.4% and 43.8% respectively. Prevalence of AKI in T1DM patients with and without DKA was 65.2% and 21.1%. 33.3% reached AKI stage2 and 66.7% of patients reached AKI stage1. RTD was evident in 136/185(73.5%) patients (32.4% showed ATN; 11.4% P-AKI; 29.7% ATD). All patients with DKA or AKI presented with RTD. The physiological and biochemical parameters of AKI and RTD were normal again in all patients. The former within 14days and the latter within 2months, respectively. Conclusions Most patients with T1DM onset may develop AKI and/or RTD, especially if presenting with DKA. Over time the physiological and biochemical parameters of AKI/RTD normalize in all patients.

scholarly journals Leonurine alleviates ferroptosis in cisplatin-induced acute kidney injury by activating the Nrf2 signaling pathway

2021 ◽  
Author(s):  
Jianqiang HU ◽  
Wenjing Gu ◽  
Ning Ma ◽  
Xiaoye Fan ◽  
Xinxin Ci
Keyword(s):  
Lipid Peroxidation ◽  
Acute Kidney Injury ◽  
Signaling Pathway ◽  
Lipid Peroxide ◽  
Kidney Injury ◽  
Iron Accumulation ◽  
Protective Effects ◽  
Nrf2 Signaling Pathway

Background and purpose: Increasing evidence suggests that ferroptosis plays a key role in the pathophysiology of acute kidney injury induced by cisplatin. The Nrf2 signaling pathway regulates oxidative stress and lipid peroxidation and positively regulates cisplatin-induced AKI (CI-AKI). However, Nrf2 and its activator leonurine on ferroptosis after CI-AKI remain unclear. Experimental Approach: The anti-ferroptotic effects of Nrf2 and its activator leonurine were assessed using a mouse model of cisplatin-induced AKI. In vitro, the potential effects of leonurine on erastin- and RSL3-induced HK-2 human PTEC ferroptosis were examined. Key Results: As expected, Nrf2 deletion induced ferroptosis-related protein expression and iron accumulation in vivo, further aggravating CI-AKI. The Nrf2 activator leonurine prevented iron accumulation and lipid peroxidation and inhibited ferroptosis in vitro, while these effects were abolished in siNrf2-treated cells. Moreover, leonurine potently ameliorated cisplatin-induced renal damage, as indicated by the assessment of SCr, BUN, KIM-1, and NGAL. Importantly, leonurine activated the Nrf2 antioxidative signaling pathway and prohibited changes in ferroptosis-related morphological and biochemical indicators, such as the MDA level, SOD and GSH depletion and GPX4 and xCT downregulation, in CI-AKI. Moreover, Nrf2 KO mice were more susceptible to ferroptosis after CI-AKI than control mice, and the protective effects of leonurine on AKI and ferroptosis were largely abolished in Nrf2 KO mice. Conclusion and Implications: These data suggest that the renal protective effects of Nrf2 and its activator leonurine on CI-AKI are achieved at least partially by inhibiting lipid peroxide-mediated ferroptosis and highlight the potential of leonurine as a CI-AKI treatment.

scholarly journals More than a simple biomarker: the role of NGAL in cardiovascular and renal diseases

2018 ◽  
Vol 132 (9) ◽  
pp. 909-923 ◽  
Author(s):  
Mathieu Buonafine ◽  
Ernesto Martinez-Martinez ◽  
Frédéric Jaisser
Keyword(s):  
Acute Kidney Injury ◽  
Current Knowledge ◽  
Kidney Injury ◽  
Renal Diseases ◽  
Tubular Damage ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Disease States ◽  
Growing Body ◽  
Neutrophil Gelatinase

Neutrophil gelatinase-associated lipocalin (NGAL) is a small circulating protein that is highly modulated in a wide variety of pathological situations, making it a useful biomarker of various disease states. It is one of the best markers of acute kidney injury, as it is rapidly released after tubular damage. However, a growing body of evidence highlights an important role for NGAL beyond that of a biomarker of renal dysfunction. Indeed, numerous studies have demonstrated a role for NGAL in both cardiovascular and renal diseases. In the present review, we summarize current knowledge concerning the involvement of NGAL in cardiovascular and renal diseases and discuss the various mechanisms underlying its pathological implications.

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