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Tempol AND Kidney

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https://www.readbyqxmd.com/read/29870982/tempol-protects-against-acute-renal-injury-by-regulating-pi3k-akt-mtor-and-gsk3%C3%AE-signaling-cascades-and-afferent-arteriolar-activity
#1
Gensheng Zhang, Qin Wang, Wenwen Wang, Minghua Yu, Suping Zhang, Nan Xu, Suhan Zhou, Xiaoyun Cao, Xiaodong Fu, Zufu Ma, Ruisheng Liu, Jianhua Mao, En Yin Lai
BACKGROUND/AIMS: Free radical scavenger tempol is a protective antioxidant against ischemic injury. Tubular epithelial apoptosis is one of the main changes in the renal ischemia/reperfusion (I/R) injury. Meanwhile some proteins related with apoptosis and inflammation are also involved in renal I/R injury. We tested the hypothesis that tempol protects against renal I/R injury by activating protein kinase B/mammalian target of rapamycin (PKB, Akt/mTOR) and glycogen synthase kinase 3β (GSK3β) pathways as well as the coordinating apoptosis and inflammation related proteins...
May 30, 2018: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29846114/kidney-dysfunction-in-the-low-birth-weight-murine-adult-implications-of-oxidative-stress
#2
Wasan Abdulmahdi, May M Rabadi, Edson Jules, Yara Marghani, Noor Marji, Jessica Leung, Frank Fan Zhang, Avi Siani, Tamar Siskind, Kiara Vedovino, Nazrul Chowdhury, Miroslav Sekulic, Brian B Ratliff
Maternal undernutrition during pregnancy leads to low birth weight (LBW) neonates that have a reduced kidney nephron endowment and higher morbidity as adults. Using a severe combined caloric and protein restricted mouse model of MUN to generate LBW mice, we examined the progression of renal insufficiency in LBW adults. Through 6 months of age, LBW males experienced greater albuminuria (ELISA analysis), a more rapid onset of glomerular hypertrophy and a worse survival rate than LBW females. In contrast, both genders experienced a comparable progressive decline in renal vascular density (immunofluorescence analysis), renal blood flow (Laser-Doppler flowmetry analysis), glomerular filtration rate (FITC-sinistrin clearance analysis), and a progressive increase in systemic blood pressure (measured via tail-cuff method)...
May 30, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29619879/cisplatin-induced-oxidative-stress-stimulates-renal-fas-ligand-shedding
#3
Hitesh Soni, Damian Kaminski, Rajashekhar Gangaraju, Adebowale Adebiyi
Acute kidney injury (AKI), a significant complication of cisplatin chemotherapy is associated with reactive oxygen species (ROS)-dependent renal cell death, but the cellular targets of ROS in cisplatin nephrotoxicity are not fully resolved. Here, we investigated cisplatin-induced oxidative renal damage and tested the hypothesis that ROS-dependent shedding of death activator Fas ligand (FasL) occurs in cisplatin nephropathy. We show that intraperitoneal injection of sulfobutyl ether-β-cyclodextrin (Captisol™)-solubilized cisplatin elevated the level of lipid peroxidation product malondialdehyde in mouse kidneys and urinary concentration of oxidative DNA damage biomarker 8-hydroxy-2'-deoxyguanosine...
November 2018: Renal Failure
https://www.readbyqxmd.com/read/29507270/antioxidative-effects-of-tempol-on-mitochondrial-dysfunction-in-diabetic-nephropathy
#4
Akram Ranjbar, Nejat Kheiripour, Hassan Ghasemi, Mohamad Ali Seif Rabiei, Farahnaz Dadras, Farhad Khoshjou
INTRODUCTION: Oxidative stress has a well-known role in diabetic nephropathy, and mitochondria are the major source of reactive oxygen species production. This study aimed to assess the effect of tempol, a superoxide dismutase mimetic agent, on mitochondrial antioxidant enzymes and cell viability in diabetic nephropathy. MATERIALS AND METHODS: Adult male Wistar rats were divided into 4 groups of 7 animals. Diabetes mellitus was induced by injection of streptozotocin in 2 groups, the rat in one of which were also treated with tempol for 4 weeks...
March 2018: Iranian Journal of Kidney Diseases
https://www.readbyqxmd.com/read/29465305/glomerular-hyperpermeability-after-acute-unilateral-ureteral-obstruction-effects-of-tempol-nos-rhoa-and-rac-1-inhibition
#5
Julia Dolinina, Anna Rippe, Peter Bentzer, Carl M Öberg
It is well known that proteinuria following urinary tract obstruction is mainly of a tubular nature. Whether there are also changes in glomerular permeability is however unknown. In this study we compared glomerular sieving coefficients (θ) of polydisperse fluorescein isothiocyanate (FITC)-Ficoll 70/400 following 120 or 180 min unilateral ureteral obstruction (UUO) in anesthetized Sprague-Dawley rats. Samples were collected from the obstructed kidney at 5, 15 and 30 minutes post-release and analyzed by means of high pressure size-exclusion chromatography (HP-SEC)...
February 21, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29359965/tempol-a-superoxide-dismutase-mimetic-drug-prevents-chronic-ischemic-renal-injury-in-two-kidney-one-clip-hypertensive-rats
#6
Douglas Vq Nunes, Cristiane A Costa, Graziele F De Bem, Viviane Sc Cordeiro, Izabelle B Santos, Lenize Crm Carvalho, Alessandro K Jordão, Anna C Cunha, Vitor F Ferreira, Roberto S Moura, Angela C Resende, Dayane T Ognibene
Tempol, a superoxide dismutase-mimetic drug, has been shown to attenuate radical-induced damage, exerting beneficial effects in the animal models of oxidative stress and hypertension. This study evaluated the effect of Tempol on renal structural and functional alterations in two-Kidney, one-Clip hypertensive rats. In this study, young male Wistar rats had the left kidney clipped (2K1C), and sham-operated animals (Sham) were used as controls. Animals received Tempol (1mmol/L in drinking water) or vehicle for 5 weeks...
January 23, 2018: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/29207011/astragaloside-iv-prevents-kidney-injury-caused-by-iatrogenic-hyperinsulinemia-in-a-streptozotocin%C3%A2-induced-diabetic-rat-model
#7
Ke-Qiang He, Wei-Zu Li, Xiao-Qing Chai, Yan-Yan Yin, Yan Jiang, Wei-Ping Li
Diabetic patients are able to manage their blood glucose with exogenous insulin but, ultimately, remain at risk of diabetic nephropathy (DN). Long‑term use of insulin may lead to iatrogenic hyperinsulinemia, which has been suggested to cause kidney injury. However, there are no effective interventions for iatrogenic hyperinsulinemia leading to kidney damage. In the present paper, the hypothesis that astragaloside IV (AS‑IV), a novel saponin purified from Astragalus membranaceus (Fisch) Bunge, may prevent DN in iatrogenic hyperinsulinemic diabetic rats through antioxidative and anti‑inflammatory mechanisms was investigated...
February 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29158353/blood-pressure-control-by-a-secreted-fgfbp1-fibroblast-growth-factor-binding-protein
#8
Elena Tassi, En Yin Lai, Lingli Li, Glenn Solis, Yifan Chen, William E Kietzman, Patricio E Ray, Anna T Riegel, William J Welch, Christopher S Wilcox, Anton Wellstein
Fibroblast growth factors (FGFs) participate in organ development and tissue maintenance, as well as the control of vascular function. The paracrine-acting FGFs are stored in the extracellular matrix, and their release is controlled by a secreted FGF-binding protein (FGF-BP, FGFBP1, and BP1) that modulates FGF receptor signaling. A genetic polymorphism in the human FGFBP1 gene was associated with higher gene expression and an increased risk of familial hypertension. Here, we report on the effects of inducible BP1 expression in a transgenic mouse model...
January 2018: Hypertension
https://www.readbyqxmd.com/read/29146611/smooth-muscle-selective-nuclear-factor-%C3%AE%C2%BAb-inhibition-reduces-phosphate-induced-arterial-medial-calcification-in-mice-with-chronic-kidney-disease
#9
Tadashi Yoshida, Maho Yamashita, Chihiro Horimai, Matsuhiko Hayashi
BACKGROUND: Hyperphosphatemia is a major factor promoting the formation of arterial medial calcification in chronic kidney disease (CKD). However, arterial medial calcification begins to occur during the early stages of CKD, when hyperphosphatemia is not yet apparent. It is predicted that other factors also play a role. The aim of the present study was to determine the role of pro-inflammatory nuclear factor-κB (NF-κB) signaling in smooth muscle cells (SMCs) for phosphate-induced arterial medial calcification in CKD mice...
November 16, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29070570/hypoxia-reoxygenation-enhances-murine-afferent-arteriolar-vasoconstriction-by-angiotensin-ii
#10
Tamara Pahlitzsch, Zhi Zhao Liu, Amira Al-Masri, Diana Braun, Stefanie Dietze, Pontus B Persson, Wolf-Hagen Schunck, Maximilian Blum, Eckehardt Kupsch, Marion Ludwig, Andreas Patzak
We tested the hypothesis that hypoxia-reoxygenation (H/R) augments vasoreactivity to angiotensin II (ANG II). In particular, we compared an in situ live kidney slice model with isolated afferent arterioles (C57Bl6 mice) to assess the impact of tubules on microvessel response. Hematoxylin and eosin staining was used to estimate slice viability. Arterioles in the slices were located by differential interference contrast microscopy, and responses to vasoactive substances were assessed. Cytosolic calcium transients and NADPH oxidase (NOX) mRNA expression were studied in isolated afferent arterioles...
March 1, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28544543/acute-toll-like-receptor-4-activation-impairs-rat-renal-microvascular-autoregulatory-behaviour
#11
J P Van Beusecum, S Zhang, A K Cook, E W Inscho
AIM: Little is known about how toll-like receptor 4 (TLR4) influences the renal microvasculature. We hypothesized that acute TLR4 stimulation with lipopolysaccharide (LPS) impairs afferent arteriole autoregulatory behaviour, partially through reactive oxygen species (ROS). METHODS: We assessed afferent arteriole autoregulatory behaviour after LPS treatment (1 mg kg(-1) ; i.p.) using the in vitro blood-perfused juxtamedullary nephron preparation. Autoregulatory behaviour was assessed by measuring diameter responses to stepwise changes in renal perfusion pressure...
November 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28438648/the-superoxide-dismutase-mimetic-tempol-blunts-diabetes-induced-upregulation-of-nadph-oxidase-and-endoplasmic-reticulum-stress-in-a-rat-model-of-diabetic-nephropathy
#12
Miles J De Blasio, Anand Ramalingam, Anh H Cao, Darnel Prakoso, Ji-Ming Ye, Raelene Pickering, Anna M D Watson, Judy B de Haan, David M Kaye, Rebecca H Ritchie
Endoplasmic reticulum (ER) stress contributes to progression of diabetic nephropathy, which promotes end-stage renal failure in diabetic patients. This study was undertaken to investigate the actions of tempol and ramipril, pharmacological agents that target the consequences of NADPH oxidase, on diabetic nephropathy in a rat model of type 1 diabetes, with an emphasis on markers of ER stress. Male Sprague-Dawley rats were injected intravenously with a single bolus of streptozotocin (55mg/kg) to induce type 1 diabetes...
July 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28397867/oxidative-stress-causes-hypertension-and-activation-of-nuclear-factor-%C3%AE%C2%BAb-after-high-fructose-and-salt-treatments
#13
Waleska C Dornas, Leonardo M Cardoso, Maísa Silva, Natália L S Machado, Deoclécio A Chianca, Andréia C Alzamora, Wanderson G Lima, Vincent Lagente, Marcelo E Silva
There is evidence that diets rich in salt or simple sugars as fructose are associated with abnormalities in blood pressure regulation. However, the mechanisms underlying pathogenesis of salt- and fructose-induced kidney damage and/or consequent hypertension yet remain largely unexplored. Here, we tested the role of oxidative state as an essential factor along with high salt and fructose treatment in causing hypertension. Fischer male rats were supplemented with a high-fructose diet (20% in water) for 20 weeks and maintained on high-salt diet (8%) associate in the last 10 weeks...
April 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28396118/superoxide-and-hydrogen-peroxide-counterregulate-myogenic-contractions-in-renal-afferent-arterioles-from-a-mouse-model-of-chronic-kidney-disease
#14
Lingli Li, En Yin Lai, Zaiming Luo, Glenn Solis, Kathy K Griendling, W Robert Taylor, Pedro A Jose, Anton Wellsten, William J Welch, Christopher S Wilcox
Myogenic contractions protect kidneys from barotrauma but are impaired in chronic kidney disease (CKD). Since myogenic contractions are enhanced by superoxide but impaired by hydrogen peroxide, we tested the hypothesis that they are counterregulated by superoxide and H2O2 from NOX2/p47phox and/or NOX4/POLDIP2 in CKD. Myogenic contraction in isolated perfused afferent arterioles from mice with surgical 5/6 nephrectomy or sham operations fed a 6% sodium chloride diet was measured directly while superoxide and H2O2 were measured by fluorescence microscopy...
April 7, 2017: Kidney International
https://www.readbyqxmd.com/read/28337250/podocyte-injury-and-albuminuria-in-experimental-hyperuricemic-model-rats
#15
Shinichiro Asakawa, Shigeru Shibata, Chikayuki Morimoto, Takeshi Shiraishi, Takashi Nakamura, Yoshifuru Tamura, Takanori Kumagai, Makoto Hosoyamada, Shunya Uchida
Although hyperuricemia is shown to accelerate chronic kidney disease, the mechanisms remain unclear. Accumulating studies also indicate that uric acid has both pro- and antioxidant properties. We postulated that hyperuricemia impairs the function of glomerular podocytes, resulting in albuminuria. Hyperuricemic model was induced by oral administration of 2% oxonic acid, a uricase inhibitor. Oxonic acid caused a twofold increase in serum uric acid levels at 8 weeks when compared to control animals. Hyperuricemia in this model was associated with the increase in blood pressure and the wall-thickening of afferent arterioles as well as arcuate arteries...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28277985/indoxyl-sulfate-potentiates-endothelial-dysfunction-via-reciprocal-role-for-reactive-oxygen-species-and-rhoa-rock-signaling-in-5-6-nephrectomized-rats
#16
Shuang Chu, Xiaodong Mao, Hengjiang Guo, Li Wang, Zezheng Li, Yang Zhang, Yunman Wang, Hao Wang, Xuemei Zhang, Wen Peng
Accumulative indoxyl sulfate (IS) retained in chronic kidney disease (CKD) can potentiate vascular endothelial dysfunction, and herein, we aim at elucidating the underlying mechanisms from the perspective of possible association between reactive oxygen species (ROS) and RhoA/ROCK pathway. IS-treated nephrectomized rats are administered with antioxidants including NADPH oxidase inhibitor apocynin, SOD analog tempol, and mitochondrion-targeted SOD mimetic mito-TEMPO to scavenge ROS, or ROCK inhibitor fasudil to obstruct RhoA/ROCK pathway...
March 2017: Free Radical Research
https://www.readbyqxmd.com/read/28263291/iron-suppresses-erythropoietin-expression-via-oxidative-stress-dependent-hypoxia-inducible-factor-2-alpha-inactivation
#17
Keisuke Oshima, Yasumasa Ikeda, Yuya Horinouchi, Hiroaki Watanabe, Hirofumi Hamano, Yoshitaka Kihira, Seiji Kishi, Yuki Izawa-Ishizawa, Licht Miyamoto, Tasuku Hirayama, Hideko Nagasawa, Keisuke Ishizawa, Koichiro Tsuchiya, Toshiaki Tamaki
Renal anemia is a major complication in chronic kidney disease (CKD). Iron supplementation, as well as erythropoiesis-stimulating agents, are widely used for treatment of renal anemia. However, excess iron causes oxidative stress via the Fenton reaction, and iron supplementation might damage remnant renal function including erythropoietin (EPO) production in CKD. EPO gene expression was suppressed in mice following direct iron treatment. Hypoxia-inducible factor-2 alpha (HIF-2α), a positive regulator of the EPO gene, was also diminished in the kidney of mice following iron treatment...
May 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28203527/superoxide-increases-angiotensin-ii-at1-receptor-function-in-human-kidney-2-cells
#18
Mohammad Saleem, Indira Pokkunuri, Mohammad Asghar
The redox-sensitive Sp family transcription factor has been linked to the regulation of angiotensin II type 1 receptor (AT1R). However, the exact mechanism of AT1R regulation in renal cells is poorly understood. We tested the specificity of reactive oxygen species (ROS), superoxide vs. hydrogen peroxide (H2O2), and the specific role of Sp3 transcription factor, if any, in the regulation of AT1R in human kidney cells (HK2 cells). Superoxide dismutase (SOD) inhibitor diethyldithiocarbamate (DETC), but not H2O2 treatment, increased fluorescence levels of superoxide probe dihydroethidium (DHE)...
December 2016: FEBS Open Bio
https://www.readbyqxmd.com/read/28168814/targeting-multiple-pathways-reduces-renal-and-cardiac-fibrosis-in-rats-with-subtotal-nephrectomy-followed-by-coronary-ligation
#19
N R Oosterhuis, L G Bongartz, M C Verhaar, C Cheng, Y J Xu, A van Koppen, M J Cramer, R Goldschmeding, C A Gaillard, P A Doevendans, B Braam, J A Joles
AIM: Multiple interacting pathways contribute to progression of renal and cardiac damage in chronic kidney disease followed by chronic heart failure (renocardiac syndrome). We hypothesized that simultaneous pharmacological modulation of critical pathways implicated in renocardiac syndrome would effectively reduce fibrosis in and preserve function of heart and kidney. METHODS: Rats were subjected to subtotal nephrectomy followed 9 weeks later by coronary artery ligation...
July 2017: Acta Physiologica
https://www.readbyqxmd.com/read/28069660/antioxidant-treatment-attenuates-lactate-production-in-diabetic-nephropathy
#20
Christoffer Laustsen, Per Mose Nielsen, Thomas Stokholm Nørlinger, Haiyun Qi, Uffe Kjærgaard Pedersen, Lotte Bonde Bertelsen, Jakob Appel Østergaard, Allan Flyvbjerg, Jan Henrik Ardenkjær-Larsen, Fredrik Palm, Hans Stødkilde-Jørgensen
The early progression of diabetic nephropathy is notoriously difficult to detect and quantify before the occurrence of substantial histological damage. Recently, hyperpolarized [1-(13)C]pyruvate has demonstrated increased lactate production in the kidney early after the onset of diabetes, implying increased lactate dehydrogenase activity as a consequence of increased nicotinamide adenine dinucleotide substrate availability due to upregulation of the polyol pathway, i.e., pseudohypoxia. In this study, we investigated the role of oxidative stress in mediating these metabolic alterations using state-of-the-art hyperpolarized magnetic resonance (MR) imaging...
January 1, 2017: American Journal of Physiology. Renal Physiology
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