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Tempol AND Kidney

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https://www.readbyqxmd.com/read/28203527/superoxide-increases-angiotensin-ii-at1-receptor-function-in-human-kidney-2-cells
#1
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
#2
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...
November 7, 2016: Acta Physiologica
https://www.readbyqxmd.com/read/28069660/antioxidant-treatment-attenuates-lactate-production-in-diabetic-nephropathy
#3
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
https://www.readbyqxmd.com/read/28052871/myoglobin-facilitates-angiotensin-ii-induced-constriction-of-renal-afferent-arterioles
#4
Zhi Zhao Liu, Susanne Mathia, Tamara Margit Pahlitzsch, Inggrid Christine Wennysia, Pontus B Persson, En Yin Lai, Anica Högner, Min Ze Xu, Rudolf Schubert, Christian Rosenberger, Andreas Patzak
Vasoconstriction plays an important role in the development of acute kidney injury in rhabdomyolysis. We hypothesized that myoglobin enhances the angiotensin II (Ang II) response in afferent arterioles by increasing superoxide and reducing nitric oxide (NO) bioavailability. Afferent arterioles of C57Bl6 mice were isolated perfused and vasoreactivity was analyzed using video microscopy. NO bioavailability, superoxide concentration in the vessels wall, and changes in cytosolic calcium were measured using fluorescence techniques...
January 4, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28042546/tempol-effect-on-epithelial-mesenchymal-transition-induced-by-hyperglycemia
#5
Mohammad Jafari, Farahnaz Dadras, Hamid Reza Ghadimipour, Mohamad Ali Seif Rabiei, Farhad Khoshjou
BACKGROUND: One of common mechanisms in pathophysiology of chronic kidney diseases is epithelial-mesenchymal transition (EMT). On the other hand oxidative stress has been known to participate in kidney damage of diabetic nephropathy (DN). OBJECTIVES: We studied if tempol, a well-known antioxidant agent, can ameliorate EMT in DN induced in male rats. MATERIALS AND METHODS: Twenty-seven male rats were equally divided in to 4 groups. Group I (control or C), group II (diabetic or D), group III (T) rats which was given tempol (100 mg/kg/day) by gavages for 28 days and group IV (D&T) was diabetic rats that also received same dose of tempol...
January 2017: Journal of Nephropathology
https://www.readbyqxmd.com/read/28030955/reno-cerebral-reflex-activates-the-renin-angiotensin-system-promoting-oxidative-stress-and-renal-damage-after-ischemia-reperfusion-injury
#6
Wei Cao, Aiqing Li, Jiawen Li, Chunyi Wu, Shuang Cui, Zhanmei Zhou, Youhua Liu, Christopher S Wilcox, Fan Fan Hou
AIMS: A kidney-brain interaction has been described in acute kidney injury, but the mechanisms are uncertain. Since we recently described a reno-cerebral reflex, we tested the hypothesis that renal ischemia-reperfusion injury (IRI) activates a sympathetic reflex that interlinks the renal and cerebral renin-angiotensin axis to promote oxidative stress and progression of the injury. RESULTS: Bilateral ischemia-reperfusion activated the intrarenal and cerebral, but not the circulating, renin-angiotensin system (RAS), increased sympathetic activity in the kidney and the cerebral sympathetic regulatory regions, and induced brain inflammation and kidney injury...
January 31, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/27907022/nicotine-induces-podocyte-apoptosis-through-increasing-oxidative-stress
#7
Xiqian Lan, Rivka Lederman, Judith M Eng, Seyedeh Shadafarin Marashi Shoshtari, Moin A Saleem, Ashwani Malhotra, Pravin C Singhal
BACKGROUND: Cigarette smoking plays an important role in the progression of chronic kidney disease (CKD). Nicotine, one of the major components of cigarette smoking, has been demonstrated to increase proliferation of renal mesangial cells. In this study, we examined the effect of nicotine on podocyte injury. METHODS: To determine the expression of nicotinic acetylcholine receptors (nAChR subunits) in podocytes, cDNAs and cell lysate of cultured human podocytes were used for the expression of nAChR mRNAs and proteins, respectively; and mouse renal cortical sections were subjected to immunofluorescant staining...
2016: PloS One
https://www.readbyqxmd.com/read/27754002/js-ish-isn-1-oxidative-stress-the-kidney-and-hypertension-clinical-implications
#8
Christopher Wilcox
OBJECTIVE: CKD progression is accelerated by hypertension and impaired myogenic responses (MRs) of renal afferent arterioles leading to renal barotrauma. We tested the hypothesis that reactive oxygen species (ROS) underlie both these processes and that ROS metabolism by tempol would thereby protect kidneys. DESIGN AND METHODS: Rat and mouse 5/6 nephrectomy models of reduced renal mass (RRM) vs sham were fed high salt for 3 months during BP telemetry. Individual afferent arterioles were isolated and perfused...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27753890/ish-nia-os-05-interleukin-6-transactivation-of-the-mineralocorticoid-receptor
#9
Brandi Wynne, Trinity Kronk, Otor Al-Khalili, Benjamin Ko, Franziska Theilig, Douglas Eaton, Robert Hoover
OBJECTIVE: Hypertension is characterized by increased sodium reabsorption along the aldosterone-sensitive distal nephron (ASDN) and systemic inflammation. Interleukin-6 (IL-6) is a possible mediator, signaling via the transmembrane IL-6 receptor alpha (IL-6Rα); however, whether IL-6Rα is present in the distal convoluted tubule (DCT) is unknown. Increased sodium reabsorption is not always correlated with increased aldosterone (Aldo). Thus, understanding how Aldo-independent sodium reabsorption occurs is critical...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27643236/ish-nia-os-05-interleukin-6-transactivation-of-the-mineralocorticoid-receptor
#10
Brandi Wynne, Trinity Kronk, Otor Al-Khalili, Benjamin Ko, Franziska Theilig, Douglas Eaton, Robert Hoover
OBJECTIVE: Hypertension is characterized by increased sodium reabsorption along the aldosterone-sensitive distal nephron (ASDN) and systemic inflammation. Interleukin-6 (IL-6) is a possible mediator, signaling via the transmembrane IL-6 receptor alpha (IL-6Rα); however, whether IL-6Rα is present in the distal convoluted tubule (DCT) is unknown. Increased sodium reabsorption is not always correlated with increased aldosterone (Aldo). Thus, understanding how Aldo-independent sodium reabsorption occurs is critical...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27642913/js-ish-isn-1-oxidative-stress-the-kidney-and-hypertension-clinical-implications
#11
Christopher Wilcox
OBJECTIVE: CKD progression is accelerated by hypertension and impaired myogenic responses (MRs) of renal afferent arterioles leading to renal barotrauma. We tested the hypothesis that reactive oxygen species (ROS) underlie both these processes and that ROS metabolism by tempol would thereby protect kidneys. DESIGN AND METHODS: Rat and mouse 5/6 nephrectomy models of reduced renal mass (RRM) vs sham were fed high salt for 3 months during BP telemetry. Individual afferent arterioles were isolated and perfused...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27630759/lower-superoxide-dismutase-2-sod2-protein-content-in-mononuclear-cells-is-associated-with-better-survival-in-patients-with-hemodialysis-therapy
#12
Katharina Krueger, Jianlin Shen, Alexandra Maier, Martin Tepel, Alexandra Scholze
Mitochondrial superoxide dismutase 2 (SOD2) converts superoxide anions to hydrogen peroxide and oxygen. Human data on SOD2 protein content in chronic kidney disease (CKD) are sparse and mortality data are lacking. We investigated SOD2 protein content in monocytes from patients with hemodialysis therapy (n = 81), CKD stage 1-5 (n = 120), and healthy controls (n = 13) using in-cell Western assays. SOD2 protein decreased from CKD stage 1 until stage 4 whereas it increased again in stage 5 with and without hemodialysis...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/27560781/effects-of-single-and-combined-losartan-and-tempol-treatments-on-oxidative-stress-kidney-structure-and-function-in-spontaneously-hypertensive-rats-with-early-course-of-proteinuric-nephropathy
#13
Danijela Karanovic, Jelica Grujic-Milanovic, Zoran Miloradovic, Milan Ivanov, Djurdjica Jovovic, Una-Jovana Vajic, Maja Zivotic, Jasmina Markovic-Lipkovski, Nevena Mihailovic-Stanojevic
Oxidative stress has been widely implicated in both hypertension and chronic kidney disease (CKD). Hypertension is a major risk factor for CKD progression. In the present study we have investigated the effects of chronic single tempol (membrane-permeable radical scavenger) or losartan (angiotensin II type 1 receptor blocker) treatment, and their combination on systemic oxidative status (plasma thiobarbituric acid-reactive substances (pTBARS) production, plasma antioxidant capacity (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid, pABTS), erythrocyte antioxidant enzymes activities) and kidney oxidative stress (kTBARS, kABTS, kidney antioxidant enzymes activities), kidney function and structure in spontaneously hypertensive rats (SHR) with the early course of adriamycin-induced nephropathy...
2016: PloS One
https://www.readbyqxmd.com/read/27489120/oxidative-stress-is-involved-in-the-renal-dysfunction-induced-by-sinoaortic-denervation-in-rats
#14
Yan Sun, Jiao Fan, Dong Chai, Minghua Zhang
The hypothesis that oxidative stress contributes to renal dysfunction in sinoaortically denervated (SAD) rats was investigated. Rats were sinoaortically denervated and received treatment with tempol (0.5 mmol/L in drinking water) for 8 weeks. Although the tempol treatment of the SAD rats had no significant effect on blood pressure or blood pressure viability, it significantly ameliorated the renal dysfunction as indicated by increases in renal blood flow (RBF) and the glomerular filtration rate (GFR) and reductions in plasma creatinine, blood urea nitrogen (BUN), the urine albumin excretion rate (UAE), and the glomerular sclerosis score (GSS)...
October 1, 2016: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27471738/tempol-effects-on-diabetic-nephropathy-in-male-rats
#15
Akram Ranjbar, Hassan Ghasemi, Mahdi Hatami, Farahanaz Dadras, Tavakol Heidary Shayesteh, Farhad Khoshjou
INTRODUCTION: Diabetic nephropathy (DN) is the most common cause of the chronic kidney disease in the world. Oxidative stress on the other hand has a major and well known role in its pathophysiology. OBJECTIVES: The aim of the study is to figure out if tempol, a synthetic antioxidant agent, modifies DN and to determine its relevance to changes of serum oxidative biomarkers. MATERIALS AND METHODS: Twenty-seven male rats were equally divided in to 4 groups (7 rats for each group)...
2016: Journal of Renal Injury Prevention
https://www.readbyqxmd.com/read/27454938/high-salt-diet-induces-outward-remodelling-of-efferent-arterioles-in-mice-with-reduced-renal-mass
#16
L Zhao, Y Gao, X Cao, D Gao, S Zhou, S Zhang, X Cai, F Han, C S Wilcox, L Li, E Y Lai
AIM: The glomerular filtration rate (GFR) falls progressively in chronic kidney disease (CKD) which is caused by a reduction in the number of functional nephrons. The dysfunctional nephron exhibits a lower glomerular capillary pressure that is induced by an unbalance between afferent and efferent arteriole. Therefore, we tested the hypothesis that oxidative stress induced by CKD differentially impairs the structure or function of efferent vs. afferent arterioles. METHODS: C57BL/6 mice received sham operations (sham) or 5/6 nephrectomy (RRM) and three months of normal- or high-salt diet or tempol...
March 2017: Acta Physiologica
https://www.readbyqxmd.com/read/27383506/aliskiren-and-l-arginine-treatments-restore-depressed-baroreflex-sensitivity-and-decrease-oxidative-stress-in-renovascular-hypertension-rats
#17
Vinicius Mengal, Paulo Hm Silva, Renata V Tiradentes, Cintia H Santuzzi, Simone A de Almeida, Gabriela C Sena, Nazare S Bissoli, Glaucia R Abreu, Sonia A Gouvea
Renovascular hypertension is characterized by increased angiotensin II and oxidative stress, and by endothelial dysfunction. The purpose of this study was to test whether the administration of aliskiren (ALSK) and l-arginine (l-ARG) would restore impaired baroreflex sensitivity and reduce oxidative stress in a rat renovascular hypertension model. Hypertension was induced by clipping the left renal artery, and the following five groups were created: SHAM; two-kidney, 1-clip (2K1C); 2K1C plus ALSK (ALSK); 2K1C plus l-ARG (l-ARG); and 2K1C plus ALSK+l-ARG (ALSK+l-ARG)...
November 2016: Hypertension Research: Official Journal of the Japanese Society of Hypertension
https://www.readbyqxmd.com/read/27112166/zomepirac-acyl-glucuronide-is-responsible-for-zomepirac-induced-acute-kidney-injury-in-mice
#18
Atsushi Iwamura, Katsuhito Watanabe, Sho Akai, Tsubasa Nishinosono, Koichi Tsuneyama, Shingo Oda, Toshiyuki Kume, Tsuyoshi Yokoi
Glucuronidation, an important phase II metabolic route, is generally considered to be a detoxification pathway. However, acyl glucuronides (AGs) have been implicated in the toxicity of carboxylic acid drugs due to their electrophilic reactivity. Zomepirac (ZP) was withdrawn from the market because of adverse effects such as renal toxicity. Although ZP is mainly metabolized to acyl glucuronide (ZP-AG) by UDP-glucuronosyltransferase, the role of ZP-AG in renal toxicity is unknown. In this study, we established a ZP-induced kidney injury mouse model by pretreatment with tri-o-tolyl phosphate (TOTP), a nonselective esterase inhibitor, and l-buthionine-(S,R)-sulfoximine (BSO), a glutathione synthesis inhibitor...
July 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/27078869/tempol-improves-xanthine-oxidoreductase-mediated-vascular-responses-to-nitrite-in-experimental-renovascular-hypertension
#19
Gustavo H Oliveira-Paula, Lucas C Pinheiro, Danielle A Guimaraes, Sandra O Conde Tella, Ana L Furlan Blanco, Celio D Angelis, Alan N Schechter, Jose E Tanus-Santos
Upregulation of xanthine oxidoreductase (XOR) increases vascular reactive oxygen species (ROS) levels and contributes to nitroso-redox imbalance. However, XOR can generate nitric oxide (NO) from nitrite, and increased superoxide could inactivate NO formed from nitrite. This study tested the hypothesis that XOR contributes to the cardiovascular effects of nitrite in renovascular hypertension, and that treatment with the antioxidant tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl) improves XOR-mediated effects of nitrite...
August 2016: Redox Biology
https://www.readbyqxmd.com/read/27032566/impact-of-pamam-delivery-systems-on-signal-transduction-pathways-in-vivo-modulation-of-erk1-2-and-p38-map-kinase-signaling-in-the-normal-and-diabetic-kidney
#20
Saghir Akhtar, Bashayer Al-Zaid, Ahmed Z El-Hashim, Bindu Chandrasekhar, Sreeja Attur, Ibrahim F Benter
The in vivo impact of two generation 6 cationic polyamidoamine (PAMAM) dendrimers on cellular signaling via extracellular-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (p38 MAPK), as well as their relationship to epidermal growth factor receptor (EGFR), were studied in the normal and/or diabetic rat kidney. A single 10mg/kg/i.p administration of Polyfect (PF; with an intact branching architecture) or Superfect (SF; with a fragmented branching architecture) modulated renal ERK1/2 and p38 MAPK phosphorylation in a dendrimer-specific and animal model-dependent manner...
December 5, 2016: International Journal of Pharmaceutics
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