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Kidney ischemia/reperfusion

Ling Hou, Gang Chen, Biao Feng, Xu-Sheng Zhang, Xiu-Fen Zheng, Ying Xiang, Guang-Yuan Zhao, Wei-Ping Min
Tumor necrosis factor-alpha (TNF-α) has been found to be centrally involved in the development of ischemia-reperfusion injury (IRI)-induced inflammation and apoptosis. Knockdown of TNF-α gene using small interfering RNA (siRNA) may protect renal IRI. Renal IRI was induced in mice by clamping the left renal pedicle for 25 or 35 min. TNF-α siRNA was administered intravenously to silence the expression of TNF-α. The therapeutic effects of siRNA were evaluated in terms of renal function, histological examination, and overall survival following lethal IRI...
October 2016: Journal of Huazhong University of Science and Technology. Medical Sciences
Ming-Zhi Zhang, Xin Wang, Yinqiu Wang, Aolei Niu, Suwan Wang, Chenhang Zou, Raymond C Harris
Cytokines IL-4 and IL-13 play important roles in polarization of macrophages/dendritic cells to an M2 phenotype, which is important for recovery from acute kidney injury. Both IL-4 and IL-13 activate JAK3/STAT6 signaling. In mice with diphtheria toxin receptor expression in proximal tubules (selective injury model), a relatively selective JAK3 inhibitor, tofacitinib, led to more severe kidney injury, delayed recovery from acute kidney injury, increased inflammatory M1 phenotype markers and decreased reparative M2 phenotype markers of macrophages/dendritic cells, and development of more severe renal fibrosis after diphtheria toxin administration...
October 10, 2016: Kidney International
I Lobb, J Jiang, D Lian, W Liu, A Haig, M N Saha, R Torregrossa, M E Wood, M Whiteman, A Sener
Ischemia-reperfusion injury (IRI) is unavoidably caused by loss and subsequent restoration of blood flow during organ procurement and prolonged IRI results in increased rates of delayed graft function and early graft loss. The endogenously produced gasotransmitter, hydrogen sulfide (H2 S), is a novel molecule that mitigates hypoxic tissue injury. The current study investigates the protective mitochondrial effects of H2 S during in vivo cold storage and subsequent renal transplantation (RTx) and in vitro cold hypoxic renal injury...
October 15, 2016: American Journal of Transplantation
Alaa E El-Sisi, Samia S Sokar, Sally E Abu-Risha, Hanaa A Ibrahim
Life threatening conditions characterized by renal ischemia/reperfusion (RIR) such as kidney transplantation, partial nephrectomy, renal artery angioplasty, cardiopulmonary bypass and aortic bypass surgery, continue to be among the most frequent causes of acute renal failure. The current study investigated the possible protective effects of tadalafil alone and in combination with diltiazem in experimentally-induced renal ischemia/reperfusion injury in rats. Possible underlying mechanisms were also investigated such as oxidative stress and inflammation...
October 10, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Niina K Palin, Johanna Savikko, Arja Pasternack, Jukka M Rintala, Bhanu Kalra, Shivani Mistry, Ajay Kumar, Marie-Paule Roth, Heikki Helin, Olli Ritvos
BACKGROUND: Activins are members of the TGF-beta superfamily of cytokines. They play critical roles in the onset of acute and chronic inflammatory responses. The aim of this study was to investigate how activin inhibition affects acute kidney injury and inflammation after transplantation. METHODS: The study was done in kidney transplantation and renal ischemia-reperfusion models in the rat. Soluble activin type 2 receptor (sActRIIB-Fc) was used to inhibit activin signaling...
October 12, 2016: Transplant International: Official Journal of the European Society for Organ Transplantation
Tanja Krainz, Michael M Gaschler, Chaemin Lim, Joshua R Sacher, Brent R Stockwell, Peter Wipf
Discovering compounds and mechanisms for inhibiting ferroptosis, a form of regulated, nonapoptotic cell death, has been of great interest in recent years. In this study, we demonstrate the ability of XJB-5-131, JP4-039, and other nitroxide-based lipid peroxidation mitigators to prevent ferroptotic cell death in HT-1080, BJeLR, and panc-1 cells. Several analogues of the reactive oxygen species (ROS) scavengers XJB-5-131 and JP4-039 were synthesized to probe structure-activity relationships and the influence of subcellular localization on the potency of these novel ferroptosis suppressors...
September 28, 2016: ACS Central Science
Gillian Balbir Singh, Soe Hee Ann, Jongha Park, Hyun Chul Chung, Jong Soo Lee, Eun-Sook Kim, Jung Il Choi, Jiho Lee, Shin-Jae Kim, Eun-Seok Shin
OBJECTIVE: Remote ischemic preconditioning (RIPC) induces transient episodes of ischemia by the occlusion of blood flow in non-target tissue, before a subsequent ischemia-reperfusion injury. When RIPC is applied before percutaneous coronary intervention (PCI), the kidneys may be protected against ischemia-reperfusion injury and subsequently contrast-induced acute kidney injury (CI-AKI). The aim of this study was to evaluate the efficacy of RIPC for the prevention of CI-AKI in patients with diabetes with pre-existing chronic kidney disease (CKD) undergoing elective PCI...
2016: PloS One
Ying Zhang, Qinggang Li, Dong Liu, Qi Huang, Guangyan Cai, Shaoyuan Cui, Xuefeng Sun, Xiangmei Chen
The GDF11 expression pattern and its effect on organ regeneration after acute injury in the elderly population are highly controversial topics. In our study, GDF11/8 expression increased after kidney ischemia-reperfusion injury (IRI), and the relatively lower level of GDF11/8 in the kidneys of aged mice was associated with a loss of proliferative capacity and a decline in renal repair, compared to young mice. In vivo, GDF11 supplementation in aged mice increased vimentin and Pax2 expression in the kidneys as well as the percentage of 5-ethynyl-2'-deoxyuridine (EdU)-positive proximal tubular epithelial cells...
October 5, 2016: Scientific Reports
Lin-Na Luo, De Qiong Xie, Xiao Gang Zhang, Rong Jiang
Renal ischemia-reperfusion (I/R) injury is a major cause of acute kidney injury. The pathogenetic mechanisms underlying renal I/R injury involve inflammation, oxidative stress and apoptosis. Osthole is a coumarin derivative that exhibits potential anti-inflammatory activity. The aim of the present study was to investigate the effect of osthole in renal I/R injury and its underlying mechanism. Renal I/R injury was induced by clamping the left renal artery for 45 min followed by 24 h reperfusion with the contralateral nephrectomy...
October 2016: Experimental and Therapeutic Medicine
Timothy M Williams, Andrea F Wise, Daniel S Layton, Sharon D Ricardo
BACKGROUND AND AIM: Kidney ischemia/reperfusion (IR) injury is characterised by tubular epithelial cell (TEC) death and an inflammatory response involving cytokine production and immune cell infiltration. In various kidney diseases, increased macrophage numbers correlate with injury severity and poor prognosis. However, macrophage plasticity enables a diverse range of functions, including wound healing, making them a key target for novel therapies. This study aimed to comprehensively characterise the changes in myeloid and epithelial cells and the production of cytokines throughout the experimental IR model of acute kidney injury to aid in the identification of targets to promote and enhance kidney regeneration and repair...
October 1, 2016: Nephrology
B Barrou, N Chatauret, T Hauet, R Thuret, F Kleinclauss, M-O Timsit, R Codas, X Matillon, L Badet
AIMS: To describe ischemia-reperfusion mechanisms, the impact on kidney graft and strategies developed to minimize ischemia-reperfusion damages. MATERIAL AND METHODS: An exhaustive systematic review of the scientific literature was performed in the Medline database ( and Embase ( using different associations of the following keywords: ischemia-reperfusion; organ preservation; hypothermic machine perfusion; renal transplantation...
September 29, 2016: Progrès en Urologie
Marcel P B Jansen, Diba Emal, Gwendoline J D Teske, Mark C Dessing, Sandrine Florquin, Joris J T H Roelofs
Acute kidney injury is often the result of ischemia reperfusion injury, which leads to activation of coagulation and inflammation, resulting in necrosis of renal tubular epithelial cells. Platelets play a central role in coagulation and inflammatory processes, and it has been shown that platelet activation exacerbates acute kidney injury. However, the mechanism of platelet activation during ischemia reperfusion injury and how platelet activation leads to tissue injury are largely unknown. Here we found that renal ischemia reperfusion injury in mice leads to increased platelet activation in immediate proximity of necrotic cell casts...
September 27, 2016: Kidney International
Björn Tampe, Ulrike Steinle, Désirée Tampe, Julienne L Carstens, Peter Korsten, Elisabeth M Zeisberg, Gerhard A Müller, Raghu Kalluri, Michael Zeisberg
Acute kidney injury (AKI) and progressive chronic kidney disease (CKD) are intrinsically tied syndromes. In this regard, the acutely injured kidney often does not achieve its full regenerative capacity and AKI directly transitions into progressive CKD associated with tubulointerstitial fibrosis. Underlying mechanisms of such AKI-to-CKD progression are still incompletely understood and specific therapeutic interventions are still elusive. Because epigenetic modifications play a role in maintaining tissue fibrosis, we used a murine model of ischemia-reperfusion injury to determine whether aberrant promoter methylation of RASAL1 contributes causally to the switch between physiological regeneration and tubulointerstitial fibrogenesis, a hallmark of AKI-to-CKD progression...
September 27, 2016: Kidney International
Beatriz Prieto-Moure, José M Lloris-Carsí, Mariola Belda-Antolí, Luis H Toledo-Pereyra, Dolores Cejalvo-Lapeña
Allopurinol is a well-known antioxidant that protects tissue against ischemia and reperfusion injury, blocking purine catabolism, and possibly reducing TNF-α and other cytokines. It also plays a significant role in reducing the inflammatory processes by inhibiting chemotaxis and other inflammatory mediators. The objective of this study was to define the role of allopurinol regarding kidney ischemic injury particularly as to its effect on inflammatory molecules such as TNF-α, IL-1β, and IL-6 response. One hundred and twenty five rats were subjected to warm renal ischemia...
October 3, 2016: Journal of Investigative Surgery: the Official Journal of the Academy of Surgical Research
Juan Zhan, Kun Wang, Conghui Zhang, Chunxiu Zhang, Yueqiang Li, Ying Zhang, Xiaoyan Chang, Qiaodan Zhou, Ying Yao, Yanyan Liu, Gang Xu
Grape seed proanthocyanindin extract (GSPE) is a polyphenolic bioflavonoid derived from grape seeds and has been widely studied for its potent antioxidant, anti-inflammatory and antitumor activities. HMGB1 is a newly discovered danger-associated molecular pattern (DAMP) that has potent proinflammatory effects once released by necrotic cells. However, the effect of GSPE on the HMGB1, and the relationship of those two with acute kidney injury and chronic kidney fibrosis are unknown. This study aimed to investigate the impact of GSPE on acute kidney injury and chronic fibrosis...
2016: International Journal of Molecular Sciences
Fatemeh Moslemi, Pegah Taheri, Mahdis Azimipoor, Sina Ramtin, Mostafa Hashemianfar, Ali Momeni-Ashjerdi, Fatemeh Eshraghi-Jazi, Ardeshir Talebi, Hamid Nasri, Mehdi Nematbakhsh
BACKGROUND: Renal ischemia/reperfusion (I/R) injury may be related to activity of reninangiotensin system (RAS), which is gender-related. In this study, it was attempted to compare the effect of angiotensin II (Ang II) receptor type 1 (AT1R) blockade; losartan in I/R injury in male and female rats. MATERIALS AND METHODS: Male and female Wistar rats were assigned as sham surgery, control I/R groups treated with vehicle, and case I/R groups treated with losartan (30 mg/kg)...
2016: Journal of Renal Injury Prevention
Peter Onody, Peter Aranyi, Zsolt Turoczi, Rita Stangl, Andras Fulop, Emese Dudas, Gabor Lotz, Attila Szijarto
AIMS AND OBJECTIVES: Acute renal failure is a severe complication of lower extremity major arterial reconstructions, which could even be fatal. Levosimendan is a dual-acting positive inotropic and vasodilatory agent, which is suspected to have protective effects against cardiac ischemia. However, there is no data available on lower limb or remote organ ischemic injuries therefore the aim of the study was to investigate the effect of levosimendan on lower limb ischemia-reperfusion injury and the corollary renal dysfunction...
2016: PloS One
Xialian Xu, Nana Song, Xue Zhang, Xiaoyan Jiao, Jiachang Hu, Mingyu Liang, Jie Teng, Xiaoqiang Ding
BACKGROUND: Angiogenesis contributes to the repair process after renal ischemia/reperfusion (I/R) injury. In the present study, we tested the role of miR-21 in the angiogenesis induced by hypoxia inducible factor (HIF) -1α through inhibiting a predicted target gene thrombospondin 1(TSP-1). METHODS: To stabilize HIF-1α, hypoxia (1% O2 for 24h) was performed in human umbilical vein endothelial cells (HUVECs) and cobalt chloride (CoCl2) was pretreated intraperitoneally 24h prior to renal I/R in mice...
September 27, 2016: Transplantation
Janka Bábíčková, Barbara M Klinkhammer, Eva M Buhl, Sonja Djudjaj, Mareike Hoss, Felix Heymann, Frank Tacke, Jürgen Floege, Jan U Becker, Peter Boor
Progressive renal diseases are associated with rarefaction of peritubular capillaries, but the ultrastructural and functional alterations of the microvasculature are not well described. To study this, we analyzed different time points during progressive kidney damage and fibrosis in 3 murine models of different disease etiologies. These models were unilateral ureteral obstruction, unilateral ischemia-reperfusion injury, and Col4a3-deficient mice, we analyzed ultrastructural alterations in patient biopsy specimens...
September 24, 2016: Kidney International
Shun-Yang Cheng, Yu-Hsiang Chou, Fang-Ling Liao, Chi-Chun Lin, Fan-Chi Chang, Chia-Hao Liu, Tao-Min Huang, Chun-Fu Lai, Yu-Feng Lin, Vin-Cent Wu, Tzong-Shinn Chu, Ming-Shiou Wu, Shuei-Liong Lin
Acute kidney injury (AKI) is an important risk factor for incident chronic kidney disease (CKD). Clinical studies disclose that ensuing CKD progresses after functional recovery from AKI, but the underlying mechanisms remain illusive. Using a murine model representing AKI-CKD continuum, we show angiotensin II type 1a (AT1a) receptor signaling as one of the underlying mechanisms. Male adult CD-1 mice presented severe AKI with 20% mortality within 2 weeks after right nephrectomy and left renal ischemia-reperfusion injury...
September 28, 2016: Scientific Reports
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