scholarly journals KIM-1 and GADDI-153 gene expression in paracetamol-induced acute kidney injury: effects of N-acetylcysteine, N-acetylmethionine, and N-acetylglucosamine

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Nahed A. Mohamed ◽  
Mohammed H. Hassan ◽  
Tahia H. Saleem ◽  
Sotohy A. Mohamed ◽  
Marwa El-Zeftawy ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Male Rats ◽  
Clinical Event ◽  
Serum Urea ◽  
Biochemical Alterations ◽  
Excretory Function ◽  
Genetic Mechanisms ◽  
Kidney Injury Molecule 1

Abstract Objectives Acute kidney injury (AKI) is a critical clinical event characterized by a reduction in the excretory function of the kidneys. N-acetylcysteine (NAC), N-acetylmethionine (NAM) and N-acetylglucosamine (NAG) are antioxidants with scanty known genetic mechanisms. We aimed to assess both kidney injury molecule-1 (KIM-1) and growth-arrested DNA damage-inducible gene-153 (GADD-153) genes expression in paracetamol (PA) induced AKI. Also, to recognize whether NAC, NAM and/or NAG have roles in altering the expression of these genes for ameliorating the AKI induced by PA. Methods The present preliminary study achieved the AKI model by oral administration of PA therapeutic dose for 15 days in experimental male rats. Serum urea, creatinine, and renal oxidative stress parameters were analyzed. Genetic expression of KIM-1 and GADD-153 were determined using real time-PCR. Results Significant elevations of serum urea, creatinine and nitric oxide in renal tissue after PA administration; however, total thiol content was reduced. In addition, both KIM-1 and GADD-153 were upregulated. These biochemical alterations were improved after using NAC and partially after NAM; however, NAG had little effect. Conclusions Up-regulation of both KIM-1 and GADD-153 occur in AKI induced by PA, which was significantly reversed by NAC.

scholarly journals The Effects of Two Different Dietary Regimens During Exercise On Outcome of Experimental Acute Kidney Injury

2021 ◽  
Author(s):  
Nazanin Sabet ◽  
Zahra Soltani ◽  
Mohammad Khaksari ◽  
Alireza Raji- amirhasani
Keyword(s):  
Acute Kidney Injury ◽  
Transforming Growth Factor ◽  
Kidney Injury ◽  
Exercise Group ◽  
Urinary Albumin ◽  
Serum Urea ◽  
Kidney Weight ◽  
Excretory Function ◽  
Total Antioxidant ◽  
Tgf Β1

Abstract Introduction: Acute kidney injury (AKI) is a syndrome characterized by rapid loss of excretory function of kidney. One of the molecules considered in the treatment of renal failure is the silent information regulator (SIRT1). In this study, the effect of two different diets during exercise on AKI was investigated. Materials and Methods: A number of rats were randomly divided into four groups; control without exercise, control with exercise, exercise + calorie restriction (CR), and exercise + time restriction (TR). Each group was divided into two subgroups of without AKI and with AKI (six rats in each group). Endurance exercise and diets were implemented before AKI. Serum urea and creatinine, urinary albumin, kidney malondialdehyde (MDA), total antioxidant capacity (TAC), transforming growth factor (TGF-β1), and SIRT1 levels, glomerular filtration rate (GFR) and relative kidney weight were measured before and 48 h after AKI induction.Results: After induction of kidney injury, serum urea and creatinine, urinary albumin, kidney MDA and TGF-β1 levels and relative kidney weight increased in rats with both previous exercise and no previous exercise (p <0.001), while GFR, and kidney TAC and SIRT1 levels decreased (p <0.001). These changes after AKI were less in the group with previous exercise than in the group that had no exercise (p <0.001). The TR diet during exercise caused a less increase in serum urea (p <0.001) and creatinine (p <0.05), and urinary albumin (p <0.01) levels after injury compared to the just exercise group. Also, both CR and TR diets during exercise caused less change in MDA (p <0.01, p <0.05, respectively) and TAC (p <0.001, p <0.05, respectively) levels compared to just exercise group. Conclusion: The results showed that exercise alone had no effect on preventing function impairment of kidney, oxidative stress, inflammation and also SIRT1 alteration following AKI in athletes, although these indexes were less among those with exercise than those without exercise. However, when the CR and TR diets were implemented during exercise, strong renoprotective effects appeared, and the protective effect of TR diet was greater.

Evaluating the Proposed Mechanism by Which Atorvastatin Can Protect Renal Tissue against Contrast Media: An Animal study

2019 ◽  
pp. 75-84
Keyword(s):  
Contrast Media ◽  
Kidney Injury ◽  
Saline Group ◽  
Pleiotropic Effect ◽  
Renal Tissue ◽  
Male Rats ◽  
Dependent Manner ◽  
Group 2 ◽  
Dose Dependent ◽  
Media Group

Contrast- induced nephropathy (CIN) is an elevation of serum creatinine of ≥ 0.5 mg/dL from baseline after two to three days of exposure to contrast substance if there is no other cause for acute kidney injury. Atorvastatin may protect normal kidney physiology from contrast- induced kidney injury by effects unrelated to hypolipidemia termed pleiotropic effect by decline of endothelin production, angiotensin system down regulation, and under expression of endothelial adhesion molecules. This study was conducted to assess the strategy by which atorvastatin can achieve protective effect for kidneys after exposure to contrast media in an animal model. A 40 male rats were distributed randomly into 4 groups; ten rats for each: group (1): given normal saline; group (2): CIN group given iopromide as contrast media; group (3): given atorvastatin (20mg/kg) and iopromide; and group (4): given atorvastatin (40mg/kg) and iopromide. Blood collected by cardiac puncture for detection of serum glutathione, malondialdehyde, matrix metalloproteinase-9, and interleukin-18. The results have shown a significant increase in inflammatory and oxidative stress markers in contrast media group, and significant reduction in these markers in atorvastatin treated groups, in a dose-dependent manner. As conclusion, atorvastatin mechanism for protection against CIN in a dose-dependent manner can mediate by anti-inflammatory and antioxidant effects.

scholarly journals Endothelial progenitor cells-derived exosomal microRNA-21-5p alleviates sepsis-induced acute kidney injury by inhibiting RUNX1 expression

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Yue Zhang ◽  
Hongdong Huang ◽  
Wenhu Liu ◽  
Sha Liu ◽  
Xue Yan Wang ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Endothelial Glycocalyx ◽  
Endothelial Progenitor ◽  
Marker Proteins ◽  
Related Transcription Factor

AbstractThe role of microRNA-21-5p (miR-21-5p) in sepsis-induced acute kidney injury (AKI) has been seldom discussed. Therefore, the objective of this present study was to investigate the mechanism of endothelial progenitor cells-derived exosomes (EPCs-exos) in sepsis-induced AKI via miR-21-5p/runt-related transcription factor 1 (RUNX1) axis. miR-21-5p was downregulated and RUNX1 was upregulated in the kidney of cecal ligation and puncture (CLP) rats, and miR-21-5p targeted RUNX1. Elevation of miR-21-5p improved renal function and renal tissue pathological damage, attenuated serum inflammatory response, as well as reduced apoptosis and oxidative stress response in renal tissues, and regulated endothelial glycocalyx damage marker proteins syndecan-1 and heparanase-1 in CLP rats. Overexpression of RUNX1 abolished the impacts of elevated miR-21-5p in CLP rats. Also, EPCs-exos upregulated miR-21-5p expression, and functioned similar to elevation of miR-21-5p for CLP rats. Downregulating miR-21-5p partially reversed the effects of EPCs-exos on sepsis-induced AKI. Collectively, our study suggests that EPCs release miR-21-5p-containing exosomes to alleviate sepsis-induced AKI through RUNX1 silencing.

scholarly journals DNA demethylase Tet2 suppresses cisplatin-induced acute kidney injury

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yinwu Bao ◽  
Mengqiu Bai ◽  
Huanhuan Zhu ◽  
Yuan Yuan ◽  
Ying Wang ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Signaling Pathway ◽  
Cell Injury ◽  
Inflammatory Responses ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Clinical Samples ◽  
Mice Model ◽  
Expression Levels ◽  
Ppar Signaling

AbstractDemethylase Tet2 plays a vital role in the immune response. Acute kidney injury (AKI) initiation and maintenance phases are marked by inflammatory responses and leukocyte recruitment in endothelial and tubular cell injury processes. However, the role of Tet2 in AKI is poorly defined. Our study determined the degree of renal tissue damage associated with Tet2 gene expression levels in a cisplatin-induced AKI mice model. Tet2-knockout (KO) mice with cisplatin treatment experienced severe tubular necrosis and dilatation, inflammation, and AKI markers’ expression levels than the wild-type mice. In addition, the administration of Tet2 plasmid protected Tet2-KO mice from cisplatin-induced nephrotoxicity, but not Tet2-catalytic-dead mutant. Tet2 KO was associated with a change in metabolic pathways like retinol, arachidonic acid, linolenic acid metabolism, and PPAR signaling pathway in the cisplatin-induced mice model. Tet2 expression is also downregulated in other AKI mice models and clinical samples. Thus, our results indicate that Tet2 has a renal protective effect during AKI by regulating metabolic and inflammatory responses through the PPAR signaling pathway.

scholarly journals A zebrafish model of infection-associated acute kidney injury

2018 ◽  
Vol 315 (2) ◽  
pp. F291-F299 ◽  
Author(s):  
Xiaoyan Wen ◽  
Liyan Cui ◽  
Seth Morrisroe ◽  
Donald Maberry ◽  
David Emlet ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Unmet Need ◽  
Kidney Injury ◽  
Edwardsiella Tarda ◽  
Adult Zebrafish ◽  
Zebrafish Model ◽  
Pericardial Edema ◽  
Kidney Injury Molecule 1 ◽  
Dose Dependent

Sepsis-associated acute kidney injury (S-AKI) independently predicts mortality among critically ill patients. The role of innate immunity in this process is unclear, and there is an unmet need for S-AKI models to delineate the pathophysiological response. Mammals and zebrafish ( Danio rerio) share a conserved nephron structure and homologous innate immune systems, making the latter suitable for S-AKI research. We introduced Edwardsiella tarda to the zebrafish. Systemic E. tarda bacteremia resulted in sustained bacterial infection and dose-dependent mortality. A systemic immune reaction was characterized by increased mRNA expressions of il1b, tnfa, tgfb1a, and cxcl8-l1 ( P < 0.0001, P < 0.001, P < 0.001, and P < 0.01, respectively). Increase of host stress response genes ccnd1 and tp53 was observed at 24 h postinjection ( P < 0.0001 and P < 0.05, respectively). Moderate E. tarda infection induced zebrafish mortality of over 50% in larvae and 20% in adults, accompanied by pericardial edema in larvae and renal dysfunction in both larval and adult zebrafish. Expression of AKI markers insulin-like growth factor-binding protein-7 (IGFBP7), tissue inhibitor of metalloproteinases 2 (TIMP-2), and kidney injury molecule-1 (KIM-1) was found to be significantly increased in the septic animals at the transcription level ( P < 0.01, P < 0.05, and P < 0.05) and in nephric tubules compared with noninfected animals. In conclusion, we established a zebrafish model of S-AKI induced by E. tarda injection, with both larval and adult zebrafish showing nephron injury in the setting of infection.

scholarly journals Gene Microarray Integrated with High-Throughput Proteomics for the Discovery of Transthyretin in Rhabdomyolysis-Induced Acute Kidney Injury

2017 ◽  
Vol 43 (4) ◽  
pp. 1673-1688 ◽  
Author(s):  
Ou Li ◽  
Xiaodong Geng ◽  
Qian Ma ◽  
Weiwei Wang ◽  
Ran Liu ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Western Blotting ◽  
Kidney Injury ◽  
Physical Exertion ◽  
Renal Tissue ◽  
Gene Microarray ◽  
Absolute Quantitation ◽  
Gene And Protein Expression ◽  
Isobaric Tagging

Background/Aims: Rhabdomyolysis, one of the leading causes of acute kidney injury (AKI), develops after trauma, drug toxicity, infections, burns, and physical exertion. The aim of this study was to investigate differences in gene and protein expression to elucidate the pathogenesis of rhabdomyolysis (RM)-induced AKI. Methods: In this study, we used glycerol induced renal injury as a model of RM-induced AKI. Affymetrix U133 plus 2.0 microarrays were used to perform gene microarray analysis. Isobaric tagging with related and absolute quantitation (iTRAQ) labeling mass spectrometry (MS) was applied to screen and identify differentially expressed proteins between RM-induced AKI and normal murine renal tissue. Verification experiments included immunohistochemistry (IHC), real-time PCR, Western blotting, and the measurement of ATP and ROS production. HK-2 cells were incubated in vitro with ferrous myoglobin and pcDNA-TTR, followed by assays to detect cell proliferation, ROS and apoptosis. Results: According to gene microarray and iTRAQ-MS analysis, we screened 17 common elements. After multiple analyses, we selected transthyretin (TTR) as our focus and investigated TTR in the kidney. Verification experiments with IHC confirmed differential expression levels of TTR proteins. Furthermore, Western blotting showed a stepwise decrease in TTR in AKI renal tissues. Cell-based experiments showed that overexpression of TTR could improve HK-2 cell viability and inhibit apoptosis. TTR reduced apoptosis by decreasing the accumulation of reactive oxygen species (ROS). Conclusion: This study reports a possible mechanism for RM-induced AKI and suggests that reductions in TTR could increase the generation of ROS and induce apoptosis. TTR may be a potentially valuable target for RM-induced AKI.

MO343SERUM RESPONSE FACTOR, A NOVEL EARLY DIAGNOSTIC BIOMARKER OF ACUTE KIDNEY INJURY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Long Zhao ◽  
Yan Xu
Keyword(s):  
Acute Kidney Injury ◽  
Serum Response Factor ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Diagnostic Value ◽  
Renal Tissue ◽  
Response Factor ◽  
Diagnostic Biomarker ◽  
Renal Tubular ◽  
Early Diagnostic

Abstract Background and Aims Studies have shown that serum response factor (SRF) is increased in chronic kidney injury, such as diabetic nephropathy, hyperuricemic nephropathy and renal cell carcinoma. The objective is to explore the early diagnostic value of SRF in acute kidney injury (AKI). Method AKI-related microarray data were analyzed, and the expression and location of SRF were investigated in the early phase of AKI. Results Bioinformatics results demonstrated that SRF was dramatically elevated 2-4 h after ischemia/reperfusion (I/R) in mouse renal tissue. In I/R rats, SRF was mostly expressed and located in renal tubular epithelial cells (TECs). SRF started to increase at 1 h, peaked at 3-9 h and started to decrease at 12 h after I/R. The areas under the ROC curve of renal SRF mRNA, renal SRF protein, urinary SRF, serum SRF and serum creatinine (Scr) were 87.9%, 83.0%, 81.3%, 78.8%, 68.8%, respectively. Conclusion SRF is remarkably upregulated in early (before 24 h) AKI and can replace Scr as a potential new early diagnostic biomarker of AKI.

scholarly journals Urinary kidney injury molecule-1 rapid test predicts acute kidney injury in extremely low-birth-weight neonates

2015 ◽  
Vol 78 (4) ◽  
pp. 430-435 ◽  
Author(s):  
Vesna D. Stojanović ◽  
Nenad A. Barišić ◽  
Nada M. Vučković ◽  
Aleksandra D. Doronjski ◽  
Amira E. Peco Antić
Keyword(s):  
Acute Kidney Injury ◽  
Birth Weight ◽  
Low Birth Weight ◽  
Kidney Injury ◽  
Rapid Test ◽  
Extremely Low Birth Weight ◽  
Kidney Injury Molecule 1

scholarly journals Enteral Baicalin, a Flavone Glycoside, Reduces Indicators of Cardiac Surgery-Associated Acute Kidney Injury in Rats

2018 ◽  
Vol 9 (1) ◽  
pp. 31-40 ◽  
Author(s):  
Jing Shi ◽  
Guofeng Wu ◽  
Xiaohua Zou ◽  
Ke Jiang
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Cardiac Surgery ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Myeloperoxidase Activity ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Injury Index ◽  
Sprague Dawley Rats

Background/Aims: Cardiac surgery-associated acute kidney injury (CSA-AKI) is one of the most common postoperative complications in intensive care medicine. Baicalin has been shown to have anti-inflammatory and antioxidant roles in various disorders. We aimed to test the protective effects of baicalin on CSA-AKI using a rat model. Methods: Sprague-Dawley rats underwent 75 min of cardiopulmonary bypass (CPB) with 45 min of cardioplegic arrest (CA) to establish the AKI model. Baicalin was administered at different doses intragastrically 1 h before CPB. The control and treated rats were subjected to the evaluation of different kidney injury index and inflammation biomarkers. Results: Baicalin significantly attenuated CPB/CA-induced AKI in rats, as evidenced by the lower levels of serum creatinine, serum NGAL, and Kim1. Baicalin remarkably inhibited oxidative stress, reflected in the decreased malondialdehyde and myeloperoxidase activity, and enhanced superoxide dismutase activity and glutathione in renal tissue. Baicalin suppressed the expression of IL-18 and iNOS, and activated the Nrf2/HO-1 pathway. Conclusion: Our data indicated that baicalin mediated CPB/CA-induced AKI by decreasing the oxidative stress and inflammation in the renal tissues, and that baicalin possesses the potential to be developed as a therapeutic tool in clinical use for CSA-AKI.

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