scholarly journals CO-Releasing Molecule-2 Prevents Acute Kidney Injury through Suppression of ROS-Fyn-ER Stress Signaling in Mouse Model

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Md Jamal Uddin ◽  
Jeewon Jeong ◽  
Eun Seon Pak ◽  
Hunjoo Ha
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Er Stress ◽  
Stress Responses ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Oxygen Species ◽  
Chronic Kidney Diseases ◽  
Tubular Cells ◽  
Cellular Apoptosis

Acute kidney injury (AKI) most commonly appears in critically ill patients in hospitals. AKI is characterized as a quick deterioration of kidney function and has recently been identified to be tightly interlinked with chronic kidney diseases. The emerging major mediators of AKI include oxidative stress and endoplasmic reticulum (ER) stress. Carbon monoxide (CO) attenuates oxidative stress and ER stress in various cells, while Fyn, a member of the Src kinase family, is activated by oxidative stress and contributes to ER stress in skeletal muscle. Considering these, the objective of the current research was to determine (i) the involvement of Fyn in ER stress-mediated AKI and (ii) the effect of CO-releasing molecule-2 (CORM2) on reactive oxygen species- (ROS-) Fyn-ER stress-mediated AKI. Pretreatment with CORM2 (30 mg/kg) efficiently inhibited LPS (30 mg/kg)-induced oxidative stress, inflammation, and cellular apoptosis during AKI in C57BL/6J mice. Also, CORM2 efficiently suppressed the activation of Fyn and ER stress in AKI mice. Consistently, pretreatment with CORM2 inhibited oxidative stress, Fyn activation, ER stress, inflammation, and apoptosis in LPS- or H2O2-stimulated proximal epithelial tubular cells. Fyn inhibition using siRNA or an inhibitor (PP2) significantly attenuated ER stress responses in the cells. These data suggest that CORM2 may become a potential treatment option against ROS-Fyn-ER stress-mediated AKI.

scholarly journals Chronic Kidney Diseases and Acute Kidney Injury in Patients With COVID-19: Evidence From a Meta-Analysis

2020 ◽  
Vol 7 ◽  
Author(s):  
Yangzhong Zhou ◽  
Qidong Ren ◽  
Gang Chen ◽  
Qiao Jin ◽  
Quexuan Cui ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Diseases ◽  
Meta Analysis ◽  
Kidney Injury ◽  
Chronic Kidney Diseases

scholarly journals Recent advances in renal hypoxia: insights from bench experiments and computer simulations

2016 ◽  
Vol 311 (1) ◽  
pp. F162-F165 ◽  
Author(s):  
Anita T. Layton
Keyword(s):  
Acute Kidney Injury ◽  
Blood Flow ◽  
Oxygen Consumption ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Chronic Kidney Diseases ◽  
Hypoxic Injury ◽  
Complex Interactions ◽  
Recent Advances

The availability of oxygen in renal tissue is determined by the complex interactions among a host of processes, including renal blood flow, glomerular filtration, arterial-to-venous oxygen shunting, medullary architecture, Na+ transport, and oxygen consumption. When this delicate balance is disrupted, the kidney may become susceptible to hypoxic injury. Indeed, renal hypoxia has been implicated as one of the major causes of acute kidney injury and chronic kidney diseases. This review highlights recent advances in our understanding of renal hypoxia; some of these studies were published in response to a recent Call for Papers of this journal: Renal Hypoxia.

scholarly journals A Novel Contrast-Induced Acute Kidney Injury Model Based on the 5/6-Nephrectomy Rat and Nephrotoxicological Evaluation of Iohexol and IodixanolIn Vivo

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Tong-qiang Liu ◽  
Wei-li Luo ◽  
Xiao Tan ◽  
Yi Fang ◽  
Jing Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Iodinated Contrast Media ◽  
Tubular Cells ◽  
Iodinated Contrast ◽  
Injury Model ◽  
Ablative Surgery ◽  
And Oxidative Stress

Contrast-induced acute kidney injury (CI-AKI) is a serious complication in patients after administration of iodinated contrast media. Proper animal models of CI-AKI can help understand the mechanisms involved and prevent the disorder. We used the 5/6-nephrectomized (NE) rat to develop a CI-AKI model and to evaluate differences in the toxic effects on the kidney between iohexol and iodixanol. We found that six weeks after ablative surgery was the preferred time to induce CI-AKI. We compared multiple pretreatment plans and found that dehydration for 48 hours before iodixanol (320, 10 mL/kg) administration was optimal to induce CI-AKI in the 5/6 NE rats. Compared with iodixanol, iohexol induced a significantly greater reduction in renal function, severe renal tissue damage, intrarenal hypoxia, and apoptotic tubular cells. Iohexol and iodixanol resulted in similarly marked increases in levels of inflammation and oxidative stress. In summary, the 5/6 NE rat combined with dehydration for 48 hours is a useful pretreatment to establish a novel and reliable CI-AKI model. Iohexol induced more severe CI-AKI than iodixanol in this model.

scholarly journals Perilipin 2 Impacts Acute Kidney Injury via Regulation of PPARα

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Sujuan Xu ◽  
Edward Lee ◽  
Zhaoxing Sun ◽  
Xiaoyan Wang ◽  
Ting Ren ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Acute Kidney Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Renal Tumors ◽  
Tubular Cells ◽  
Proximal Tubular ◽  
Perilipin 2 ◽  
Renal Proximal Tubular

Renal ischemia-reperfusion (I/R) can induce oxidative stress and injury via the generation of reactive oxygen species (ROS). Renal proximal tubular cells are susceptible to oxidative stress, and the dysregulation of renal proximal tubular cellular homeostasis can damage cells via apoptotic pathways. A recent study showed that the generation of ROS can increase perilipin 2 (Plin2) expression in HepG2 cells. Some evidence has also demonstrated the association between Plin2 expression and renal tumors. However, the underlying mechanism of Plin2 in I/R-induced acute kidney injury (AKI) remains elusive. Here, using a mouse model of I/R-induced AKI, we found that ROS generation was increased and the expression of Plin2 was significantly upregulated. An in vitro study further revealed that the expression of Plin2, and the generation of ROS were significantly upregulated in primary tubular cells treated with hydrogen peroxide. Accordingly, Plin2 knockdown decreased apoptosis in renal proximal tubular epithelial cells treated with hydrogen peroxide, which depended on the activation of peroxisome proliferator-activated receptor α (PPARα). Overall, the present study demonstrated that Plin2 is involved in AKI; knockdown of this marker might limit apoptosis via the activation of PPARα. Consequently, the downregulation of Plin2 could be a novel therapeutic strategy for AKI.

scholarly journals The Kidney Injury Induced by Short-Term PM2.5 Exposure and the Prophylactic Treatment of Essential Oils in BALB/c Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Yining Zhang ◽  
Qiujuan Li ◽  
Mengxiong Fang ◽  
Yanmin Ma ◽  
Na Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Inflammatory Response ◽  
Essential Oils ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Kidney Damage ◽  
Ros Generation ◽  
Short Term ◽  
Ras Activation

PM2.5 is well known as a major environmental pollutant; it has been proved to be associated with kidney diseases. The kidney damage involves oxidative stress and/or inflammatory response. NOX4 is a major source of reactive oxygen species (ROS) generation in the kidney, and the excessive generation of ROS is recognized to be responsible for oxidative stress. To elucidate whether short-term PM2.5 exposure could induce kidney damage, we exposed BALB/c mice to PM2.5 intratracheally and measured the biomarkers of kidney injury (KIM-1, cystatin C), oxidative stress (MDA, SOD-1, and HO-1), and inflammatory response (NF-κB, TNF-α). Acute kidney damage and excessive oxidative stress as well as transient inflammatory response were observed after PM2.5 installation. The overexpression of some components of the angiotensin system (RAS) after PM2.5 exposure illustrated that RAS may be involved in PM2.5-induced acute kidney injury. CEOs (compound essential oils) have been widely used because of their antioxidant and anti-inflammation properties. Treatment with CEOs substantially attenuated PM2.5-induced acute kidney injury. The suppression of RAS activation was significant and earlier than the decrease of oxidative stress and inflammatory response after CEOs treatment. We hypothesized that CEOs could attenuate the acute kidney injury by suppressing the RAS activation and subsequently inhibit the oxidative stress and inflammatory response.

scholarly journals Troponins, Acute Coronary Syndrome and Renal Disease: From Acute Kidney Injury Through End-stage Kidney Disease

2019 ◽  
Vol 14 (3) ◽  
pp. 187-190
Author(s):  
Debasish Banerjee ◽  
Charlotte Perrett ◽  
Anita Banerjee
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Left Ventricular ◽  
End Stage Kidney Disease ◽  
Chronic Kidney Diseases ◽  
Coronary Syndrome ◽  
End Stage ◽  
Cardiac Troponins

The diagnosis of acute coronary syndromes (ACS) is heavily dependent on cardiac biomarker assays, particularly cardiac troponins. ACS, particularly non-ST segment elevation MI, are more common in patients with acute kidney injury, chronic kidney disease (CKD) and end-stage kidney disease (ESKD), are associated with worse outcomes than in patients without kidney disease and are often difficult to diagnose and treat. Hence, early accurate diagnosis of ACS in kidney disease patients is important using easily available tools, such as cardiac troponins. However, the diagnostic reliability of cardiac troponins has been suboptimal in patients with kidney disease due to possible decreased clearance of troponin with acute and chronic kidney impairment and low levels of troponin secretion due to concomitant cardiac muscle injury related to left ventricular hypertrophy, inflammation and fibrosis. This article reviews the metabolism and utility of cardiac biomarkers in patients with acute and chronic kidney diseases. Cardiac troponins are small peptides that accumulate in both acute and chronic kidney diseases due to impaired excretion. Hence, troponin concentrations rise and fall with acute kidney injury and its recovery, limiting their use in the diagnosis of ACS. Troponin concentrations are chronically elevated in CKD and ESKD, are associated with poor prognosis and decrease the sensitivity and specificity for diagnosis of ACS. Yet, the evidence indicates that the use of high-sensitivity troponins can confirm or exclude a diagnosis of ACS in the emergency room in a significant proportion of kidney disease patients; those patients in whom the results are equivocal may need longer in-hospital assessment.

scholarly journals PARK7 Protects Against Chronic Kidney Injury and Renal Fibrosis by Inducing SOD2 to Reduce Oxidative Stress

2021 ◽  
Vol 12 ◽  
Author(s):  
Lijun Yin ◽  
Honglin Li ◽  
Zhiwen Liu ◽  
Wenwen Wu ◽  
Juan Cai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Apoptosis ◽  
Renal Fibrosis ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Ros Production ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Chronic Kidney Injury ◽  
Renal Tubular

Renal fibrosis is the final common pathway to chronic kidney diseases regardless of etiology. Parkinson disease protein 7 (PARK7) is a multifunctional protein involved in various cellular processes, but its pathophysiological role in kidneys remain largely unknown. Here, we have determined the role of PARK7 in renal fibrosis and have further elucidated the underlying mechanisms by using the in vivo mouse model of unilateral ureteric obstruction (UUO) and the in vitro model of transforming growth factor-b (TGFB1) treatment of cultured kidney proximal tubular cells. PARK7 decreased markedly in atrophic kidney tubules in UUO mice, and Park7 deficiency aggravated UUO-induced renal fibrosis, tubular cell apoptosis, ROS production and inflammation. In vitro, TGFB1 treatment induced fibrotic changes in renal tubular cells, which was accompanied by alterations of PARK7. Park7 knockdown exacerbated TGFB1-induced fibrotic changes, cell apoptosis and ROS production, whereas Park7 overexpression or treatment with ND-13 (a PARK7-derived peptide) attenuated these TGFB1-induced changes. Mechanistically, PARK7 translocated into the nucleus of renal tubular cells following TGFB1 treatment or UUO, where it induced the expression of SOD2, an antioxidant enzyme. Taken together, these results indicate that PARK7 protects against chronic kidney injury and renal fibrosis by inducing SOD2 to reduce oxidative stress in tubular cells.

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