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Tempol AND Kidney

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https://www.readbyqxmd.com/read/27907022/nicotine-induces-podocyte-apoptosis-through-increasing-oxidative-stress
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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-remodeling-of-efferent-arterioles-in-mice-with-reduced-renal-mass
#10
Liang Zhao, Yufang Gao, Xiaoyun Cao, Danchen Gao, Suhan Zhou, Suping Zhang, Xiaoxia Cai, Feng Han, Christopher S Wilcox, Lingli Li, En Yin 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 versus afferent arterioles. METHODS: C57BL/6 mice received sham operations (sham) or 5/6 nephrectomy (RRM) and 3 months of normal or high salt diet or tempol...
July 25, 2016: 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
#11
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)...
July 7, 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
#12
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
#13
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
#14
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...
March 23, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27001421/augmentation-of-phosphate-induced-osteo-chondrogenic-transformation-of-vascular-smooth-muscle-cells-by-homoarginine
#15
Ioana Alesutan, Martina Feger, Rashad Tuffaha, Tatsiana Castor, Katharina Musculus, Salvatore S Buehling, Christian L Heine, Makoto Kuro-O, Burkert Pieske, Kurt Schmidt, Andreas Tomaschitz, Winfried Maerz, Stefan Pilz, Andreas Meinitzer, Jakob Voelkl, Florian Lang
AIMS: Reduced homoarginine plasma levels are associated with unfavourable cardiovascular outcome in chronic kidney disease (CKD). Cardiovascular events in CKD are fostered by vascular calcification, an active process promoted by hyperphosphatemia and involving osteo-/chondrogenic transformation of vascular smooth muscle cells (VSMCs). The present study explored the effect of homoarginine on phosphate-induced osteo-/chondrogenic signalling and vascular calcification. METHODS AND RESULTS: Experiments were performed in hyperphosphatemic klotho-hypomorphic mice (kl/kl), in subtotal nephrectomy and vitamin D3-overload mouse calcification models and in primary human aortic smooth muscle cells (HAoSMCs)...
June 1, 2016: Cardiovascular Research
https://www.readbyqxmd.com/read/26894882/protective-effect-of-tempol-on-acute-kidney-injury-through-pi3k-akt-nrf2-signaling-pathway
#16
Gensheng Zhang, Qiaoling Wang, Qin Zhou, Renjun Wang, Minze Xu, Huiping Wang, Lei Wang, Christopher S Wilcox, Ruisheng Liu, En Yin Lai
BACKGROUND/AIMS: Tempol is a protective antioxidant against ischemic injury in many animal models. The molecular mechanisms are not well understood. Nuclear factor erythroid 2-related factor (Nrf2) is a master transcription factor during oxidative stress, which is enhanced by activation of protein kinase C (PKC) pathway. Another factor, tubular epithelial apoptosis, is mediated by activation of phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB, Akt) signaling pathway during renal ischemic injury...
2016: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/26823282/modulation-of-the-myogenic-mechanism-concordant-effects-of-no-synthesis-inhibition-and-o2-dismutation-on-renal-autoregulation-in-the-time-and-frequency-domains
#17
Nicholas G Moss, Tayler K Gentle, William J Arendshorst
Renal blood flow autoregulation was investigated in anesthetized C57Bl6 mice using time- and frequency-domain analyses. Autoregulation was reestablished by 15 s in two stages after a 25-mmHg step increase in renal perfusion pressure (RPP). The renal vascular resistance (RVR) response did not include a contribution from the macula densa tubuloglomerular feedback mechanism. Inhibition of nitric oxide (NO) synthase [N(G)-nitro-l-arginine methyl ester (l-NAME)] reduced the time for complete autoregulation to 2 s and induced 0...
May 1, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/26279424/tempol-a-superoxide-dismutase-mimetic-drug-ameliorates-progression-of-renal-disease-in-ckd-mice
#18
Wei Ding, Bin Wang, Minmin Zhang, Yong Gu
BACKGROUND: Oxidative stress has been implicated in the pathogenesis of chronic kidney disease (CKD) and antioxidants may ameliorate disease progression. We investigate the beneficial effect of Tempol, a superoxide dismutase-mimetic drug, on progression of disease in a mouse model of CKD. METHODS: CKD was surgically induced in c57BL/6 mice by 5/6 nephrectomy. Mice were randomly divided into 3 groups: sham group, 5/6 nephrectomized group (Nx) and Nx+Tempol (2 mmol/l in drinking water)...
2015: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/26215821/scavenging-reactive-oxygen-species-using-tempol-in-the-acute-phase-of-renal-ischemia-reperfusion-and-its-effects-on-kidney-oxygenation-and-nitric-oxide-levels
#19
Ugur Aksu, Bulent Ergin, Rick Bezemer, Asli Kandil, Dan M J Milstein, Cihan Demirci-Tansel, Can Ince
BACKGROUND: Renal ischemia/reperfusion (I/R) injury is commonly seen in kidney transplantation and affects the allograft survival rates. We aimed to test our hypothesis that scavenging reactive oxygen species (ROS) with tempol would protect renal oxygenation and nitric oxide (NO) levels in the acute phase of renal I/R. METHODS: Rats were randomly divided: (1) no I/R, no tempol; (2) no I/R, but with tempol; (3) I/R without tempol; and (4) I/R with tempol. I/R was induced by 30-min clamping of the renal artery...
December 2015: Intensive Care Medicine Experimental
https://www.readbyqxmd.com/read/26180238/predicted-effects-of-nitric-oxide-and-superoxide-on-the-vasoactivity-of-the-afferent-arteriole
#20
Anita T Layton, Aurélie Edwards
We expanded a published mathematical model of an afferent arteriole smooth muscle cell in rat kidney (Edwards A, Layton, AT. Am J Physiol Renal Physiol 306: F34-F48, 2014) to understand how nitric oxide (NO) and superoxide (O(2)(-)) modulate the arteriolar diameter and its myogenic response. The present model includes the kinetics of NO and O(2)(-) formation, diffusion, and reaction. Also included are the effects of NO and its second messenger cGMP on cellular Ca²⁺ uptake and efflux, Ca²⁺-activated K⁺ currents, and myosin light chain phosphatase activity...
October 15, 2015: American Journal of Physiology. Renal Physiology
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