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Kidney ischemia/reperfusion

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https://www.readbyqxmd.com/read/29218078/extendin-4-protects-kidney-from-acute-ischemia-reperfusion-injury-through-upregulation-of-nrf2-signaling
#1
Yen-Yi Zhen, Chih-Chao Yang, Chi-Chih Hung, Chia-Chang Lee, Chen-Chang Lee, Chien-Hsing Wu, Yen-Ta Chen, Wei-Yu Chen, Kuan-Hung Chen, Hon-Kan Yip, Sheung-Fat Ko
This study tested the hypothesis that exendin-4 (Ex4) protects kidneys against ischemia-reperfusion (IR) injury mainly through upregulation of nuclear-factor erythroid 2-related factor 2 (Nrf2) signaling and downregulation of oxidative stress. Male-adult Sprague-Dawley rats (n=24) were equally divided into group 1 (sham-operated control), group 2 [IR only, ischemia (1 h)/reperfusion (72 h)] and group 3 (IR-Ex4, 10 μg/kg at 30 min, 24 h, 48 h after IR procedure). The in vitro study demonstrated that the protein expressions of phosphorylated (p)-Akt and Nrf2 were significantly progressively increased at time points of 0/0...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29212948/elevated-urinary-creld2-is-associated-with-endoplasmic-reticulum-stress-mediated-kidney-disease
#2
Yeawon Kim, Sun-Ji Park, Scott R Manson, Carlos Af Molina, Kendrah Kidd, Heather Thiessen-Philbrook, Rebecca J Perry, Helen Liapis, Stanislav Kmoch, Chirag R Parikh, Anthony J Bleyer, Ying Maggie Chen
ER stress has emerged as a signaling platform underlying the pathogenesis of various kidney diseases. Thus, there is an urgent need to develop ER stress biomarkers in the incipient stages of ER stress-mediated kidney disease, when a kidney biopsy is not yet clinically indicated, for early therapeutic intervention. Cysteine-rich with EGF-like domains 2 (CRELD2) is a newly identified protein that is induced and secreted under ER stress. For the first time to our knowledge, we demonstrate that CRELD2 can serve as a sensitive urinary biomarker for detecting ER stress in podocytes or renal tubular cells in murine models of podocyte ER stress-induced nephrotic syndrome and tunicamycin- or ischemia-reperfusion-induced acute kidney injury (AKI), respectively...
December 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/29207388/resveratrol-does-not-protect-from-ischemia-induced-acute-kidney-injury-in-an-in-vivo-rat-model
#3
Anja Bienholz, Rahel Mae Pang, Hana Guberina, Ursula Rauen, Oliver Witzke, Benjamin Wilde, Frank Petrat, Thorsten Feldkamp, Andreas Kribben
BACKGROUND/AIMS: The natural polyphenol resveratrol (RSV) has been shown to ameliorate ischemia/reperfusion (I/R)-induced damage. Therefore, a rat model of I/R-induced AKI equipped with intensive monitoring was utilized to examine direct renal protection by RSV in vivo. METHODS: AKI was induced by bilateral renal clamping (45 min) followed by reperfusion (3 h). Solvent-free RSV was continuously infused intravenously (0.056 and 0.28 mg/kg) in a total volume of 7 ml/kg/h starting from 30 min before renal clamping...
December 5, 2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29202871/mesenchymal-stem-cell-derived-extracellular-vesicles-for-kidney-repair-current-status-and-looming-challenges
#4
REVIEW
Arash Aghajani Nargesi, Lilach O Lerman, Alfonso Eirin
Novel therapies are urgently needed to address the rising incidence and prevalence of acute kidney injury (AKI) and chronic kidney disease (CKD). Mesenchymal stem/stromal cells (MSCs) have shown promising results in experimental AKI and CKD, and have been used in the clinic for more than a decade with an excellent safety profile. The regenerative effects of MSCs do not rely on their differentiation and ability to replace damaged tissues, but are primarily mediated by the paracrine release of factors, including extracellular vesicles (EVs), composed of microvesicles and exosomes...
December 4, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29197972/prognostic-value-of-intraoperative-measurements-of-renal-tissue-oxygenation-and-microcirculation-on-renal-function-in-partial-nephrectomy
#5
Matthias Maruschke, Katja Hagel, Oliver Hakenberg, Thomas Scheeren
BACKGROUND: Partial nephrectomy (PNx) can be associated with macrocirculatory and microcirculatory alterations, ultimately leading to acute kidney injury (AKI). Measuring kidney tissue oxygenation (μHbO2) and microcirculation during open PNx might be feasible to early detect these alterations and prevent postoperative AKI. METHODS: μHbO2 and microcirculation were measured in 45 patients undergoing PNx by reflectance spectrophotometry and laser Doppler flowmetry (O2C™, Lea, Germany), related to ischemia time and tumour size...
December 2, 2017: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/29197870/detection-of-acute-tubular-necrosis-using-blood-oxygenation-level-dependent-bold-mri
#6
Frederic Bauer, Jan Wald, Felix Jan Bauer, Lisa Maria Dahlkamp, Felix S Seibert, Nikolaos Pagonas, Egbert Gedat, Nina Babel, Walter Zidek, Christian von Bodman, Joachim Noldus, Dieter Liermann, Timm H Westhoff
BACKGROUND/AIMS: To date, there is no imaging technique to assess tubular function in vivo. Blood oxygen level-dependent magnetic resonance imaging (BOLD MRI) measures tissue oxygenation based on the transverse relaxation rate (R2*). The present study investigates whether BOLD MRI can assess tubular function using a tubule-specific pharmacological maneuver. METHODS: Cross sectional study with 28 participants including 9 subjects with ATN-induced acute kidney injury (AKI), 9 healthy controls, and 10 subjects with nephron sparing tumor resection (NSS) with clamping of the renal artery serving as a model of ischemia/reperfusion (I/R)-induced subclinical ATN (median clamping time 15 min, no significant decrease of eGFR, p=0...
December 4, 2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29197607/inflammatory-response-modulation-through-a-ppar%C3%AE-agonist-during-surgically-induced-visceral-ischemia-in-an-animal-model
#7
Bianca Pane, Valerio Gazzola, Giovanni Spinella, Paola Bagnato, Federica Grillo, Valerio Gaetano Vellone, Domenico Palombo
BACKGROUND: Ischemia / reperfusion (I/R) injury represents one of the most severe complications in vascular surgery where cross-clamping of the aorta and subsequent visceral ischemia are a recurrent issue. The literature describes a family of nuclear receptors, i.e., peroxisome-proliferator activated receptors (PPARs), in particular PPARγ isoform, which are important modulators of vascular inflammation resulting from I/R injury. The aim of our study is to evaluate how PPARγ agonist administration could reduce local and systemic inflammatory response after I/R injury during aortic supraceliac clamping in animal model...
November 29, 2017: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/29196613/protective-effect-of-luteolin-against-renal-ischemia-reperfusion-injury-via-modulation-of-pro-inflammatory-cytokines-oxidative-stress-and-apoptosis-for-possible-benefit-in-kidney-transplant
#8
Yan Liu, Baoxin Shi, Yi Li, Hui Zhang
BACKGROUND The acceptances and long-term outcomes of the renal transplantations are seriously jeopardized by inflammatory responses and damage to tissues. The present study intended to explicate the pharmacological effect of luteolin (LT) in renal ischemia/reperfusion (I/R) injury and the possible mechanism of action of LT. MATERIAL AND METHODS The effect of LT on the level of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in the homogenates of kidney tissues of male Swiss albino mice was determined after I/R injury...
December 2, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29187644/nanoparticle-targeting-to-the-endothelium-during-normothermic-machine-perfusion-of-human-kidneys
#9
Gregory T Tietjen, Sarah A Hosgood, Jenna DiRito, Jiajia Cui, Deeksha Deep, Eric Song, Jan R Kraehling, Alexandra S Piotrowski-Daspit, Nancy C Kirkiles-Smith, Rafia Al-Lamki, Sathia Thiru, J Andrew Bradley, Kourosh Saeb-Parsy, John R Bradley, Michael L Nicholson, W Mark Saltzman, Jordan S Pober
Ex vivo normothermic machine perfusion (NMP) is a new clinical strategy to assess and resuscitate organs likely to be declined for transplantation, thereby increasing the number of viable organs available. Short periods of NMP provide a window of opportunity to deliver therapeutics directly to the organ and, in particular, to the vascular endothelial cells (ECs) that constitute the first point of contact with the recipient's immune system. ECs are the primary targets of both ischemia-reperfusion injury and damage from preformed antidonor antibodies, and reduction of perioperative EC injury could have long-term benefits by reducing the intensity of the host's alloimmune response...
November 29, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29187590/selective-cannabinoid-2-receptor-stimulation-reduces-tubular-epithelial-cell-damage-following-renal-ischemia-reperfusion-injury
#10
Jeffrey D Pressly, Suni M Mustafa, Ammaar Abidi, Sahar Alghamdi, Pankaj Pandey, Kuldeep K Roy, Robert Doerksen, Bob M Moore, Frank Park
Ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury (AKI), which is an increasing problem in the clinic and has been associated with increased rates of mortality. Currently, therapies to treat AKI are not available, so identification of new targets which, upon diagnosis of AKI, can be modulated to ameliorate renal damage is essential. In this study, a novel cannabinoid receptor 2 (CB2) agonist, SMM-295, was designed, synthesized, and tested in vitro and in silico. In vivo testing of the CB2 agonist was performed using a mouse model of bilateral IRI, which is a common model to mimic human AKI...
November 29, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29187371/effects-of-erythropoietin-receptor-activity-on-angiogenesis-tubular-injury-and-fibrosis-in-acute-kidney-injury-a-u-shaped-relationship
#11
Mingjun Shi, Brianna Flores, Peng Li, Nancy Gillings, Kathryn L McMillan, Jianfeng Ye, Lily June-Shen Huang, Sachdev S Sidhu, Yong-Ping Zhong, Maria T Grompe, Philip R Streeter, Orson W Moe, Ming Chang Hu
Erythropoietin receptor (EpoR) is widely expressed but its renoprotective action is unexplored. To examine the role of EpoR in vivo in the kidney, we induced acute kidney injury (AKI) by ischemia-reperfusion in mice with different EpoR bioactivities in the kidney. EpoR bioactivity was reduced by knock-in of wild type human EpoR, which is hypo-functional relative to murine EpoR, and a renal tubule-specific EpoR knockout. These mice had lower EPO/EpoR activity and lower autophagy flux in renal tubules. Upon AKI induction, they exhibited worse renal function and structural damage, and more apoptosis at the acute stage (< 7 days), and slower recovery with more tubulointerstitial fibrosis at the subacute stage (14 days)...
November 29, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29185370/effect-of-nicotine-on-placental-ischemia-induced-complement-activation-and-hypertension-in-the-rat
#12
Connor F Laule, Cameron R Wing, Evan J Odean, Jacob A Wilcox, Jeffrey S Gilbert, Jean F Regal
Preeclampsia is a pregnancy-specific condition manifested by new-onset maternal hypertension with systemic inflammation, including increased innate immune system complement activation. While exact pathophysiology is unknown, evidence suggests that inadequate spiral artery invasion and resulting utero-placental insufficiency is the initiating event. Cigarette smoking during pregnancy decreases the risk of preeclampsia. Nicotine, a major component of cigarettes, stimulates the efferent cholinergic anti-inflammatory pathway through peripherally expressed nicotinic acetylcholine receptors (nAChR) and is known to attenuate ischemia-reperfusion injury in kidney and liver...
December 2017: Journal of Immunotoxicology
https://www.readbyqxmd.com/read/29181415/endothelial-stat3-modulates-protective-mechanisms-in-a-mouse-ischemia-reperfusion-model-of-acute-kidney-injury
#13
Shataakshi Dube, Tejasvi Matam, Jessica Yen, Henry E Mang, Pierre C Dagher, Takashi Hato, Timothy A Sutton
STAT3 is a transcriptional regulator that plays an important role in coordinating inflammation and immunity. In addition, there is a growing appreciation of the role STAT3 signaling plays in response to organ injury following diverse insults. Acute kidney injury (AKI) from ischemia-reperfusion injury is a common clinical entity with devastating consequences, and the recognition that endothelial alterations contribute to kidney dysfunction in this setting is of growing interest. Consequently, we used a mouse with a genetic deletion of Stat3 restricted to the endothelium to examine the role of STAT3 signaling in the pathophysiology of ischemic AKI...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/29180395/tamm-horsfall-protein-regulates-mononuclear-phagocytes-in-the-kidney
#14
Radmila Micanovic, Shehnaz Khan, Danielle Janosevic, Maya E Lee, Takashi Hato, Edward F Srour, Seth Winfree, Joydeep Ghosh, Yan Tong, Susan E Rice, Pierre C Dagher, Xue-Ru Wu, Tarek M El-Achkar
Tamm-Horsfall protein (THP), also known as uromodulin, is a kidney-specific protein produced by cells of the thick ascending limb of the loop of Henle. Although predominantly secreted apically into the urine, where it becomes highly polymerized, THP is also released basolaterally, toward the interstitium and circulation, to inhibit tubular inflammatory signaling. Whether, through this latter route, THP can also regulate the function of renal interstitial mononuclear phagocytes (MPCs) remains unclear, however...
November 27, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29180394/redirecting-tgf-%C3%AE-signaling-through-the-%C3%AE-catenin-foxo-complex-prevents-kidney-fibrosis
#15
Xi Qiao, Padmashree Rao, Yun Zhang, Lixin Liu, Min Pang, Hailong Wang, Min Hu, Xinrui Tian, Jianlin Zhang, Ye Zhao, Xin Maggie Wang, Chengshi Wang, Hong Yu, Fei Guo, Qi Cao, Yiping Wang, Yuan Min Wang, Geoff Yu Zhang, Vincent W Lee, Stephen I Alexander, Guoping Zheng, David C H Harris
TGF-β is a key profibrotic factor, but targeting TGF-β to prevent fibrosis also abolishes its protective anti-inflammatory effects. Here, we investigated the hypothesis that we can redirect TGF-β signaling by preventing downstream profibrotic interaction of β-catenin with T cell factor (TCF), thereby enhancing the interaction of β-catenin with Foxo, a transcription factor that controls differentiation of TGF-β induced regulatory T cells (iTregs), and thus, enhance anti-inflammatory effects of TGF-β In iTregs derived from EL4 T cells treated with recombinant human TGF-β1 (rhTGF-β1) in vitro, inhibition of β-catenin/TCF transcription with ICG-001 increased Foxp3 expression, interaction of β-catenin and Foxo1, binding of Foxo1 to the Foxp3 promoter, and Foxo transcriptional activity...
November 27, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29172924/pink1-prkn-park2-pathway-of-mitophagy-is-activated-to-protect-against-renal-ischemia-reperfusion-injury
#16
Chengyuan Tang, Hailong Han, Mingjuan Yan, Shiyao Zhu, Jing Liu, Zhiwen Liu, Liyu He, Jieqiong Tan, Yu Liu, Hong Liu, Lin Sun, Shaobin Duan, Youming Peng, Fuyou Liu, Xiao-Ming Yin, Zhuohua Zhang, Zheng Dong
Damaged or dysfunctional mitochondria are toxic to the cell by producing reactive oxygen species and releasing cell death factors. Therefore, timely removal of these organelles is critical to cellular homeostasis and viability. Mitophagy is the mechanism of selective degradation of mitochondria via autophagy. The significance of mitophagy in kidney diseases, including ischemic acute kidney injury (AKI), has yet to be established, and the involved pathway of mitophagy remains poorly understood. Here, we show that mitophagy is induced in renal proximal tubular cells in both in vitro and in vivo models of ischemic AKI...
November 26, 2017: Autophagy
https://www.readbyqxmd.com/read/29161807/intravenous-dextran-70-infusion-has-protective-effects-on-ischemia-reperfusion-injury-of-kidney-an-experimental-study
#17
Atilla Semercioz, Mustafa Z Temiz, Ipek Erbarut, Ugur Izol, Serdar Aykan, Murat Tuken, Engin Kandirali
BACKGROUND: Renal ischemia-reperfusion (IR) leads to alterations of tubular epithelial cells, interstitial microvasculopathy and endothelial cell dysfunction in peritubular capillaries. Although dextrans have deteriorative effects on healthy kidney, their favorable effects on post-ischemic microvascular disturbances have been demonstrated. Therefore, we aimed to investigate in vivo effects of systemic Dextran 70 administration in kidney tissue with ischemia-reperfusion injury. METHODS: Twenty-one rats were allocated as sham, IR and IR+ Dextran 70 treatment groups...
November 21, 2017: Minerva Urologica e Nefrologica, the Italian Journal of Urology and Nephrology
https://www.readbyqxmd.com/read/29160368/the-effects-of-local-ischemic-preconditioning-and-topical-hypothermia-in-renal-ischemia-reperfusion-injury-in-rats
#18
Guilherme Behrend Ribeiro, Emanuel Burck Dos Santos, Silvia Regina Bona, Pedro Guilherme Schaefer, Tuane Alves Garcez, Eduardo Brasil Rabolini, Guilherme Pereira Smaniotto, Norma Possa Marroni, Carlos Otávio Corso
PURPOSE: Topical hypothermia and local ischemic preconditioning have been shown to reduce renal ischemia-reperfusion (I/R) injury individually. We examined whether combination of both strategies lessens renal I/R injury. METHODS: Post right nephrectomy, 40 male Wistar rats were randomly assigned to five experimental protocols performed in the left kidney: topical hypothermia without ischemia (TH), warm ischemia (IR), ischemic preconditioning followed by warm ischemia (IPC+IR), cold ischemia (TH+IR), and ischemic preconditioning followed by cold ischemia (IPC+TH+IR)...
October 2017: Acta Cirúrgica Brasileira
https://www.readbyqxmd.com/read/29155898/protective-effect-of-malva-sylvestris-l-extract-in-ischemia-reperfusion-induced-acute-kidney-and-remote-liver-injury
#19
Houshang Najafi, Zeynab Mohamadi Yarijani, Saeed Changizi-Ashtiyani, Kamran Mansouri, Masoud Modarresi, Seyed Hamid Madani, Bahar Bastani
Mallow (Malva sylvestris L.) has had medicinal and therapeutic uses in addition to its oral consumption. The present study was conducted to examine the protective effect of Malva sylvestris L. extract on ischemia-reperfusion-induced kidney injury and remote organ injuries in the liver. Before ischemia-reperfusion, rats in the different groups received intraperitoneal normal saline or mallow extract at the doses of 200, 400 or 600 mg/kg of body weight. After 30-minutes of bilateral renal ischemia followed by 24-hours of reperfusion, tissue damage in the kidney and liver samples were determined through studying H&E-stained slides under a light microscope...
2017: PloS One
https://www.readbyqxmd.com/read/29150436/microvesicles-derived-from-human-wharton-s-jellymesenchymal-stem-cells-ameliorate-ischemia-reperfusion-induced-renal-fibrosis-by-releasing-from-g2-m-cell-cycle-arrest
#20
Wenxia Chen, Yongbin Yan, Chundong Song, Ying Ding, Tao Du
Studies have demonstrated that microvesicles (MVs) derived from human Wharton's Jelly mesenchymal stromal cells (hWJMSCs) could ameliorate renal ischemia/reperfusion injury (IRI), however, the underlying mechanisms were not clear yet. Here, MVs were isolated and injected intravenously into rats immediately after ischemia of the left kidney, and Erk1/2 activator HGF or inhibitor U0126 was administrated, respectively. Tubular cell proliferation and apoptosis were identified by Ki67 or TUNEL immunostaining. Masson's tri-chrome straining and alpha-smooth muscle actin (α -SMA) staining were used for assessing renal fibrosis...
November 17, 2017: Biochemical Journal
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