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Kidney ischemia/reperfusion

Li Liu, Xiaoyan Wu, Huihui Xu, Liming Yu, Xinjian Zhang, Luyang Li, Jianliang Jin, Tao Zhang, Yong Xu
A host of pathogenic factors induce acute kidney injury (AKI) leading to insufficiencies of renal function. In the present study we evaluated the role of myocardin-related transcription factor A (MRTF-A) in the pathogenesis of AKI. We report that systemic deletion of MRTF-A or inhibition of MRTF-A activity with CCG-1423 significantly attenuated AKI in mice induced by either ischemia-reperfusion or LPS injection. Of note, MRTF-A deficiency or suppression resulted in diminished renal ROS production in AKI models with down-regulation of NAPDH oxdiase 1 (NOX1) and NOX4 expression...
June 14, 2018: Biochimica et Biophysica Acta
Juan Bai, Jinyi Zhao, Dongxiao Cui, Fan Wang, Ying Song, Lianghua Cheng, Kai Gao, Jin Wang, Long Li, Shujun Li, Yanyan Jia, Aidong Wen
This study aimed to evaluate the protective effect of hydroxysafflor yellow A (HSYA) on ischemia/reperfusion (I/R)-induced acute kidney injury via the TLR4/NF-κB pathway, both in vitro and in vivo. Rats were subjected to removal of the right kidney and I/R injury to the left kidney. Rats subjected to renal I/R injury were treated with HSYA at 0.5 h prior to I/R injury. Renal function, histopathological analysis, and cells apoptosis were measured in vivo. In vitro, proximal renal tubular cells (HK-2) were subjected to hypoxia/reoxygenation (H/R)...
June 15, 2018: Scientific Reports
Alice Marino, Takuya Sakamoto, Xiao-Han Tang, Lorraine J Gudas, Roberto Levi
We previously discovered that oral treatment with AC261066, a synthetic selective agonist for the retinoic acid β2-receptor (RARβ2), decreases oxidative stress in the liver, pancreas, and kidney of mice fed a high-fat diet (HFD). Since hyperlipidemic states are causally associated with myocardial ischemia and oxidative stress, we have now investigated the effects of AC261066 in an ex-vivo ischemia/reperfusion (I/R) injury model in hearts of two prototypic dysmetabolic mice. We found that a 6-week oral treatment with AC261066 in both genetically hypercholesterolemic (ApoE-/-) and obese (HFD-fed) wild-type mice exerts protective effects when their hearts are subsequently subjected to I/R ex vivo in the absence of added drug...
June 15, 2018: Journal of Pharmacology and Experimental Therapeutics
Quanxin Li, Ziying Wang, Yan Zhang, Jiaqing Zhu, Liang Li, Xiaojie Wang, Xiaoyang Cui, Yu Sun, Wei Tang, Chengjiang Gao, Chunhong Ma, Fan Yi
There is significant progress in understanding the structure and function of NLRC5, a member of the nucleotide oligomerization domain-like receptor family. However, in the context of MHC class I gene expression, the functions of NLRC5 in innate and adaptive immune responses beyond the regulation of MHC class I genes remain controversial and unresolved. In particular, the role of NLRC5 in the kidney is unknown. NLRC5 was significantly upregulated in the kidney from mice with renal ischemia/reperfusion injury...
June 12, 2018: Kidney International
Bassim I Mohammad, Abdulla K Rahem, Najah R Hadi, Dina A Jamil, Hayder A Al-Aubaidy
Acute kidney inschemia/reperfusion (I/R) injury is characterized by an abrupt loss of kidney function, resulting in the retention of urea and other nitrogenous waste products and in the dysregulation of extracellular volume and electrolytes. Despite the advances in therapeutic techniques, the mortality and morbidity of patients remain high and have not appreciably improved. This study aims to evaluate the potential protective effect of TAK-242 on renal ischemia/reperfusion injury using an animal model. Thirty-five adult male Sprague-dawely rats (weighing 200-300), were assigned randomly into the following experimental groups (n = 7 in each group), Control (I/R), Sham (negative control), TAK-242 (5 mg/kg body weight), TAK-242 (10 mg/kg body weight) and Vehicle (DMSO)...
June 11, 2018: Biochemical and Biophysical Research Communications
Weina Wang, Aimei Wang, Guochang Luo, Fengqiao Ma, Xiaoming Wei, Yongyi Bi
Ischemia/reperfusion (I/R) is a major cause of acute kidney injury (AKI), along with delayed graft function, which can trigger chronic kidney injury by stimulating epithelial to mesenchymal transition (EMT) in the kidney canaliculus. Sphingosine 1-phosphate receptor 1 (S1P1) is a G protein-coupled receptor that is indispensable for vessel homeostasis. This study aimed to investigate the influence of S1P1 on the mechanisms underlying I/R-induced EMT in the kidney using in vivo and in vitro models. Wild-type (WT) and S1P1-overexpressing kidney canaliculus cells were subject to hypoxic conditions followed by reoxygenation in the presence or absence of FTY720-P, a potent S1P1 agonist...
June 13, 2018: Acta Biochimica et Biophysica Sinica
Kelley Núñez, Paul Thevenot, Abeer Alfadhli, Ari Cohen
The complement system anchors the innate inflammatory response by triggering both cell-mediated and antibody-mediated immune responses against pathogens. The complement system also plays a critical role in sterile tissue injury by responding to damage-associated molecular patterns. The degree and duration of complement activation may be a critical variable controlling the balance between regenerative and destructive inflammation following sterile injury. Recent studies in kidney transplantation suggest that aberrant complement activation may play a significant role in delayed graft function following transplantation, confirming results obtained from rodent models of renal ischemia/reperfusion (I/R) injury...
June 13, 2018: International Journal of Molecular Sciences
Sang Jun Han, Hongmei Li, Mihwa Kim, Mark J Shlomchik, H Thomas Lee
The role for kidney TLR9 in ischemic acute kidney injury (AKI) remains unclear. In this study, we tested the hypothesis that renal proximal tubular TLR9 activation exacerbates ischemic AKI by promoting renal tubular epithelial apoptosis and inflammation. To test this hypothesis, we generated mice lacking TLR9 in renal proximal tubules (TLR9fl/fl PEPCK Cre mice). Contrasting previous studies in global TLR9 knockout mice, mice lacking renal proximal tubular TLR9 were protected against renal ischemia/reperfusion (IR) injury, with reduced renal tubular necrosis, inflammation (decreased proinflammatory cytokine synthesis and neutrophil infiltration), and apoptosis (decreased DNA fragmentation and caspase activation) when compared with wild-type (TLR9fl/fl ) mice...
June 13, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Babak Baban, Md Nasrul Hoda, Aneeq Malik, Hesam Khodadadi, Erika Simmerman, Kumar Vaibhav, Mahmood S Mozaffari
Hallmark features of acute kidney injury (AKI) include mobilization of immune and inflammatory mechanisms culminating in tissue injury. Emerging information indicates heterogeneity of neutrophils with pro- and anti-inflammatory functions (N1 and N2, respectively). Also, regulatory T-17 (Treg17) cells curtail Th-17-mediated pro-inflammatory responses. However, the status of Treg17 cells and neutrophil phenotypes in AKI are not established. Further, cannabidiol exerts immunoregulatory effects but its impact on Treg17 cells and neutrophil subtypes is not established...
June 13, 2018: American Journal of Physiology. Renal Physiology
Laurence Black, Jeremie M Lever, Amie M Traylor, Bo Chen, Zhengqin Yang, Stephanie Esman, Yanlin Jiang, Gary Cutter, Ravindra Boddu, James George, Anupam Agarwal
Chronic kidney disease (CKD) is a condition with significant morbidity and mortality that affects 15% of adults in the United States. One cause of CKD is acute kidney injury (AKI), which commonly occurs secondary to sepsis, ischemic events, and drug-induced nephrotoxicity. Unilateral ischemia-reperfusion injury (UIRI) without contralateral nephrectomy (CLN) and repeated low dose cisplatin (RLDC) models of AKI to CKD demonstrate responses characteristic of the transition; however, previous studies have not effectively compared the pathogenesis...
June 13, 2018: American Journal of Physiology. Renal Physiology
Mingjuan Yan, Shaoqun Shu, Chunyuan Guo, Chengyuan Tang, Zheng Dong
Acute kidney injury is a medical condition characterized by kidney damage with a rapid decline of renal function, which is associated with high mortality and morbidity. Recent research has further established an intimate relationship between acute kidney injury and chronic kidney disease. Perturbations of kidney cells in acute kidney injury result in the accumulation of unfolded and misfolded proteins in the endoplasmic reticulum, leading to unfolded protein response or endoplasmic reticulum stress. In this review, we analyze the role and regulation of endoplasmic reticulum stress in acute kidney injury triggered by renal ischemia-reperfusion and cisplatin nephrotoxicity...
June 12, 2018: Annals of Medicine
Ze Liu, Hao Li, Jianqun Su, Shihui Xu, Fengxin Zhu, Jun Ai, Zheng Hu, Miaomiao Zhou, Jianwei Tian, Zhiyuan Su, Peiliang Yang, Jing Nie
AIMS: Mitochondrial fragmentation is a crucial mechanism contributing to tubular cell apoptosis during acute kidney injury (AKI). However, the mechanism of modulating mitochondrial dynamics during AKI remains unclear. Numb is a multifunction adaptor protein that is expressed in renal tubules. The aim of the present study is to study the role of Numb in mitochondrial dysfunction during AKI. RESULTS: The expression of Numb was upregulated in both ischemia-reperfusion- and cisplatin-induced AKI...
June 11, 2018: Antioxidants & Redox Signaling
Najet Hadj Abdallah, Anna Baulies, Ahlem Bouhlel, Mohamed Bejaoui, Mohamed Amine Zaouali, Safa Ben Mimouna, Imed Messaoudi, José Carlos Fernandez-Checa, Carmen García Ruiz, Hassen Ben Abdennebi
AIM: Zinc has proved its efficacy in many models of ischemia reperfusion (I/R) injury. In this study, we used zinc acexamate (ZAC) as an exogenous source of zinc against renal I/R injury and we investigated whether its protective effects are mediated by the decrease of oxidative stress, inflammation, and mitochondria induced-apoptosis. METHODS: Rats were orally pretreated with vehicle or ZAC (10 or 100 mg/kg) 24 h and 30 min prior to 1 h of bilateral renal warm ischemia and 2 h of reperfusion...
June 8, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Luzia S Sampaio, Fabio A Iannotti, Luciana Veneziani, Rosa T Borelli-Tôrres, Fabrizia De Maio, Fabiana Piscitelli, Ricardo A M Reis, Vincenzo Di Marzo, Marcelo Einicker-Lamas
LLC-PK1 cells, an immortalized epithelial cell line derived from pig renal proximal tubules, express all the major players of the endocannabinoid system (ECS) such as CB1, CB2 and TRPV1 receptor, as well as the main enzymes involved in the biosynthesis and degradation of the major endocannabinoids named 2-arachidonoylglycerol, 2-AG and anandamide, AEA. Here we investigated whether the damages caused by ischemic insult either in vitro using LLC-PK1 cells exposed to antimycin A (an inductor of ATP-depletion) or in vivo using Wistar rats in a classic renal ischemia and reperfusion (IR) protocol, lead to changes in AEA and 2-AG levels, as well as altered expression of genes from the main enzymes involved in the regulation of the ECS...
June 8, 2018: Biochemical Pharmacology
Zhiyu He, Haoyu Tang, Xinru You, Keqing Huang, Arvind Dhinakar, Yang Kang, Qiaoli Yu, Jun Wu
Ischemia-reperfusion (I/R) is a major cause of acute kidney injury (AKI), which is associated with unacceptably high mortality rates in ICU. This research was designed to explore the therapeutic effect of BAPTA-AM (1,2-Bis(2-aminophenoxy) ethane-N,N,N,N-tetraacetic acid tetrakis(acetoxymethyl ester)) nanoparticle (BA-N) on AKI. BA-N was developed by liposome strategy and characterized by standard methods. The rat model was selected and the rats were randomly allocated into four groups: (1) Normal group; (2) Sham-operated group; (3) Model group (I/R + NS); (4) BA-N treatment group (I/R + BA-N)...
May 1, 2018: Journal of Biomedical Nanotechnology
Robert A Kloner, Kevin S King, Michael Harrington
The no-reflow phenomenon refers to the observation that when an organ is made ischemic by occlusion of a large artery supplying it, restoration of patency in that artery does not restore perfusion to the microvasculature supplying the parenchyma of that organ. This has been observed following prolonged arterial occlusions in the heart (30 to 90 minutes), brain, skin, and kidney. In experimental models, zones of no-reflow in the heart are characterized by ultrastructural microvascular damage, including focal endothelial swelling obstructing the lumen of small vessels...
June 8, 2018: American Journal of Physiology. Heart and Circulatory Physiology
Mahshid Tahamtan, Vahid Sheibani, Seyed Mostafa Shid Moosavi, Majid Asadi-Shekaari, Saeed Esmaeili-Mahani, Iraj Aghaei, Mohammad Shabani
One of the most common causes of mortality in acute kidney injury is brain dysfunction. Here we investigated the possible protective effect of erythropoietin (EPO) on cognitive impairments induced by bilateral renal ischemia (BRI). Eighty male Wistar rats were allocated into 8 groups: 1, 2) Sham +V (Vehicle), 3, 4) Sham+EPO, 5, 6) BRI+V, 7, 8) BRI+EPO. The groups followed by the reperfusion periods of 24hours (24 h) and 1week (1w). EPO or saline was administrated 30 min before surgery (1000 IU/kg, i.p). The cognitive function was assessed by passive avoidance learning and Morris water maze tests...
2018: Iranian Journal of Pharmaceutical Research: IJPR
Y Chen, L Zhao, S Jiang, Z Hu, B Hu, F Tong, R Shen
BACKGROUND: The aim of this study was to determine whether the protective effects of brief and repeated ischemic postconditioning (IPoC) are associated with the modulation of cystathionine γ-lyase (CSE) expression after renal ischemia/reperfusion (I/R) injury in diabetes mellitus (DM). METHODS: We subjected diabetic rats to 45 minutes of ischemia followed by reperfusion at 24 hours. Before reperfusion, diabetic rats were treated with 3 cycles of 6 seconds of reperfusion, followed by 6 seconds of ischemia...
June 2018: Transplantation Proceedings
Héloïse Cardinal, Mélanie Dieudé, Marie-Josée Hébert
Kidney transplantation entails a high likelihood of endothelial injury. The endothelium is a target of choice for injury by ischemia-reperfusion, alloantibodies, and autoantibodies. A certain degree of ischemia-reperfusion injury inevitably occurs in the immediate posttransplant setting and can manifest as delayed graft function. Acute rejection episodes, whether T-cell or antibody-mediated, can involve the graft micro- and macrovasculature, leading to endothelial injury and adverse long-term consequences on graft function and survival...
2018: Frontiers in Immunology
Giuseppe Castellano, Rossana Franzin, Alessandra Stasi, Chiara Divella, Fabio Sallustio, Paola Pontrelli, Giuseppe Lucarelli, Michele Battaglia, Francesco Staffieri, Antonio Crovace, Giovanni Stallone, Marc Seelen, Mohamed R Daha, Giuseppe Grandaliano, Loreto Gesualdo
Pericytes are one of the principal sources of scar-forming myofibroblasts in chronic kidneys disease. However, the modulation of pericyte-to-myofibroblast transdifferentiation (PMT) in the early phases of acute kidney injury is poorly understood. Here, we investigated the role of complement in inducing PMT after transplantation. Using a swine model of renal ischemia/reperfusion (I/R) injury, we found the occurrence of PMT after 24 h of I/R injury as demonstrated by reduction of PDGFRβ+ /NG2+ cells with increase in myofibroblasts marker αSMA...
2018: Frontiers in Immunology
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