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NADPH oxidase and renal

Chihiro Kaneko, Jiro Ogura, Shunichi Sasaki, Keisuke Okamoto, Masaki Kobayashi, Kaori Kuwayama, Katsuya Narumi, Ken Iseki
BACKGROUND: A high intake of fructose increases the risk for hyperuricemia. It has been reported that long-term fructose consumption suppressed renal uric acid excretion and increased serum uric acid level. However, the effect of single administration of fructose on excretion of uric acid has not been clarified. METHODS: We used male Wistar rats, which were orally administered fructose (5g/kg). Those rats were used in each experiment at 12h after administration...
November 29, 2016: Biochimica et Biophysica Acta
Rajesh K Dutta, Vinay K Kondeti, Isha Sharma, Navdeep S Chandel, Susan E Quaggin, Yashpal S Kanwar
Overexpression of the proximal tubular enzyme myo-inositol oxygenase (MIOX) induces oxidant stress in vitro However, the relevance of MIOX to tubular pathobiology remains enigmatic. To investigate the role of MIOX in cisplatin-induced tubular AKI, we generated conditional MIOX-overexpressing transgenic (MIOX-TG) mice and MIOX-knockout (MIOX(-/-)) mice with tubule-specific MIOX overexpression or knockout, respectively. Compared with cisplatin-treated wild-type (WT) mice, cisplatin-treated MIOX-TG mice had even greater increases in urea, creatinine, and KIM-1 levels and more tubular injury and apoptosis, but these effects were attenuated in cisplatin-treated MIOX(-/-) mice...
November 28, 2016: Journal of the American Society of Nephrology: JASN
Mirandy S Li, Sherry E Adesina, Jennifer L Gooch, Robert S Hoover, Clintoria R Williams
Zn(2+) deficiency (ZnD) is comorbid with chronic kidney disease (CKD) and worsens kidney complications. Oxidative stress is implicated in the detrimental effects of ZnD. However, the sources of oxidative stress continue to be identified. Since NADPH oxidases (Nox) are the primary enzymes that contribute to renal reactive oxygen species (ROS) generation, this study's objective was to determine the role of these enzymes in ZnD-induced oxidative stress. We hypothesized that ZnD promotes Nox upregulation resulting in oxidative stress and kidney damage...
November 2, 2016: American Journal of Physiology. Cell Physiology
David Harrison
Hypertension remains an enormous health care burden that affects one third of the population. Despite its prevalence the cause of most cases of hypertension remains unknown. Our laboratory has defined a novel mechanism for hypertension involving adaptive immunity. We found that mice lacking lymphocytes (RAG-1 mice) develop blunted hypertensive responses to a variety of stimuli including chronic angiotensin II infusion, DOCA-salt challenge and norepinephrine infusion. Adoptive transfer of T cells, but not B cells, restores the hypertensive responses to these stimuli...
September 2016: Journal of Hypertension
David Harrison
Hypertension remains an enormous health care burden that affects one third of the population. Despite its prevalence the cause of most cases of hypertension remains unknown. Our laboratory has defined a novel mechanism for hypertension involving adaptive immunity. We found that mice lacking lymphocytes (RAG-1 mice) develop blunted hypertensive responses to a variety of stimuli including chronic angiotensin II infusion, DOCA-salt challenge and norepinephrine infusion. Adoptive transfer of T cells, but not B cells, restores the hypertensive responses to these stimuli...
September 2016: Journal of Hypertension
Hila Roshanravan, Eun Y Kim, Stuart E Dryer
The arachidonic acid metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) regulates renal function, including changes in glomerular function evoked during tubuloglomerular feedback (TGF). This study describes the cellular actions of 20-HETE on cultured podocytes, assessed by whole-cell recordings from cultured podocytes combined with pharmacological and cell-biological manipulations of cells. Bath superfusion of 20-HETE activates cationic currents that are blocked by the pan-TRP blocker SKF-96365 and by 50 μM La(3+), and which are attenuated after siRNA knockdown of TRPC6 subunits...
2016: Frontiers in Physiology
Cheng Wan, Hua Su, Chun Zhang
Metabolic syndrome has been linked to an increased risk of chronic kidney disease. The underlying pathogenesis of metabolic disease-related renal injury remains obscure. Accumulating evidence has shown that NADPH oxidase is a major source of intrarenal oxidative stress and is upregulated by metabolic factors leading to overproduction of ROS in podocytes, endothelial cells, and mesangial cells in glomeruli, which is closely associated with the initiation and progression of glomerular diseases. This review focuses on the role of NADPH oxidase-induced oxidative stress in the pathogenesis of metabolic disease-related renal injury...
2016: Oxidative Medicine and Cellular Longevity
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
Huibin Nie, Xia Xue, Gang Liu, Guangju Guan, Haiying Liu, Lina Sun, Long Zhao, Xueling Wang, Zhixin Chen
Nitroalkene derivative of oleic acid (OA-NO2), due to its ability to mediate revisable Michael addition, has been demonstrated to have various biological properties and become a therapeutic agent in various diseases. Though its antioxidant properties have been reported in different models of acute kidney injury (AKI), the mechanism by which OA-NO2 attenuates intracellular oxidative stress is not well investigated. Here, we elucidated the anti-oxidative mechanism of OA-NO2 in an in vitro model of renal ischemia/reperfusion (I/R) injury...
2016: Free Radical Research
Shan Gao, Byung M Park, Seung A Cha, Ui J Bae, Byung H Park, Woo H Park, Suhn H Kim
Hypertension often occurs in conjunction with insulin resistance. The purpose of this study was to evaluate whether sustained renal hypertension increases the risk of diabetes mellitus in rats, and to define the underlying mechanisms. Two-kidney, one-clip hypertensive (2K1C) rats received captopril (50 mg/kg/day), α-lipoic acid (100 mg/kg/day), or vehicle treatment for 3 months after surgery. Blood pressure was measured by tail cuff plethysmography. Oral glucose tolerance test (OGTT), immunohistochemistry, and western blotting were performed...
August 2016: Physiological Reports
Indira Pokkunuri, Quaisar Ali, Mohammad Asghar
We examined the effects and mechanism of grape powder- (GP-) mediated improvement, if any, on aging kidney function. Adult (3-month) and aged (21-month) Fischer 344 rats were treated without (controls) and with GP (1.5% in drinking water) and kidney parameters were measured. Control aged rats showed higher levels of proteinuria and urinary kidney injury molecule-1 (KIM-1), which decreased with GP treatment in these rats. Renal protein carbonyls (protein oxidation) and gp (91phox) -NADPH oxidase levels were high in control aged rats, suggesting oxidative stress burden in these rats...
2016: Oxidative Medicine and Cellular Longevity
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
Michael Hezel, Maria Peleli, Ming Liu, Christa Zollbrecht, Boye L Jensen, Antonio Checa, Alessia Giulietti, Craig E Wheelock, Jon O Lundberg, Eddie Weitzberg, Mattias Carlström
Advanced age is associated with increased risk for cardiovascular disease and type 2 diabetes. A proposed central event is diminished amounts of nitric oxide (NO) due to reduced generation by endothelial NO synthase (eNOS) and increased oxidative stress. In addition, it is widely accepted that increased angiotensin II (ANG II) signaling is also implicated in the pathogenesis of endothelial dysfunction and hypertension by accelerating formation of reactive oxygen species. This study was designed to test the hypothesis that dietary nitrate supplementation could reduce blood pressure and improve glucose tolerance in aged rats, via attenuation of NADPH oxidase activity and ANG II receptor signaling...
July 26, 2016: Free Radical Biology & Medicine
Nirlep Chhiber, Tanzeer Kaur, Surinder Singla
BACKGROUND: Oxalate and/or calcium oxalate, is known to induce free radical production, subsequently leading to renal epithelial injury. Oxidative stress and mitochondrial dysfunction have emerged as new targets for managing oxalate induced renal injury. HYPOTHESIS: Plant products and antioxidants have gained tremendous attention in the prevention of lithiatic disease. Rottlerin, a polyphenolic compound from the fruits of Mallotus phillipensis (Lam.) Müll.Arg., has shown free radical scavenging, antioxidant activity and has been reported to interfere in signaling pathways leading to inflammation and apoptosis...
September 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Abdalla M El-Mowafy, Mohamed M Katary, Chelsey Pye, Ahmed S Ibrahim, Ahmed A Elmarakby
BACKGROUND/AIM: Hepatic injury is a hallmark adverse reaction to Valproate (VPA), a common used drug in the management of numerous CNS disorders, including epilepsy. DHA has a myriad of health benefits, including renal- and hepato-protective effects. Unfortunately, however, the underpinnings of such liver-pertinent VPA- and DHA-actions remain largely undefined. Accordingly, this study attempted to unveil the cellular and molecular triggers whereby VPA evokes, while DHA abates, hepatotoxicity...
July 2016: Heliyon
Ting Yang, Christa Zollbrecht, Malin E Winerdal, Zhengbing Zhuge, Xing-Mei Zhang, Niccolo Terrando, Antonio Checa, Johan Sällström, Craig E Wheelock, Ola Winqvist, Robert A Harris, Erik Larsson, A Erik G Persson, Bertil B Fredholm, Mattias Carlström
BACKGROUND: Early-life reduction in nephron number (uninephrectomy [UNX]) and chronic high salt (HS) intake increase the risk of hypertension and chronic kidney disease. Adenosine signaling via its different receptors has been implicated in modulating renal, cardiovascular, and metabolic functions as well as inflammatory processes; however, the specific role of the A3 receptor in cardiovascular diseases is not clear. In this study, gene-modified mice were used to investigate the hypothesis that lack of A3 signaling prevents the development of hypertension and attenuates renal and cardiovascular injuries following UNX in combination with HS (UNX-HS) in mice...
July 2016: Journal of the American Heart Association
Leopoldo Raij, Runxia Tian, Jenny S Wong, John C He, Kirk N Campbell
Podocytes are the key target for injury in proteinuric glomerular diseases that result in podocyte loss, progressive focal segmental glomerular sclerosis (FSGS), and renal failure. Current evidence suggests that the initiation of podocyte injury and associated proteinuria can be separated from factors that drive and maintain these pathogenic processes leading to FSGS. In nephrotic urine aberrant glomerular filtration of plasminogen (Plg) is activated to the biologically active serine protease plasmin by urokinase-type plasminogen activator (uPA)...
December 1, 2016: American Journal of Physiology. Renal Physiology
Nadezhda N Zheleznova, Chun Yang, Allen W Cowley
Nox4 and Nox2 are the most abundant NADPH oxidases (Nox) in the kidney and have been shown to contribute to hypertension, renal oxidative stress, and injury in Dahl salt-sensitive (SS) hypertensive rats. The present study focused on the role of Nox4 and p67phox/Nox2 in the generation of H2O2 and O2 (·-) in the renal medullary thick ascending limb of Henle (mTAL) of SS rats in response to increasing luminal flow (from 5 to 20 nl/min). Nox4 and p67phox/Nox2 genes were found to be expressed in the mTAL of SS rats...
August 1, 2016: American Journal of Physiology. Renal Physiology
Xiao-Qiang Li, Wen Tian, Xiao-Xiao Liu, Kai Zhang, Jun-Cheng Huo, Wen-Juan Liu, Ping Li, Xiong Xiao, Ming-Gao Zhao, Wei Cao
Diabetic nephropathy (DN) is one of the major complications of diabetes mellitus (DM). This study aimed to explore the effects of corosolic acid (CA) on the renal damage of DM and the mechanisms behind these effects. The renoprotective effect of CA was investigated in type 1 diabetic rats and db/db mice. The kidneys and glomerular mesangial cells (GMCs) were used to study the proliferation of GMCs by immunostaining and MTT assay. Further immunoblotting, siRNA, qPCR analysis, and detecting of NADPH oxidase activity and reactive oxygen species (ROS) generation were performed to explore relevant molecular mechanisms...
2016: Scientific Reports
Kyong-Jin Jung, Kyoung-Jin Min, Jeen-Woo Park, Kwon Moo Park, Taeg Kyu Kwon
Fibrosis represents a common pathway to end-stage renal disease. Transforming growth factor-β (TGF-β) plays a critical role in the progression of kidney fibrosis. In the present study, we explored the effect of carnosic acid (CA) against TGF-β-induced fibroblast activation in vitro and unilateral ureteral obstruction (UUO)-induced kidney fibrosis in vivo. CA attenuated TGF-β-induced up-regulation of profibrogenic proteins, α-smooth muscle actin (α-SMA), collagen I (COLI), fibronectin (FN), and plasminogen activator inhibitor-1 (PAI-1) in kidney fibroblast cells (NRK-49F)...
August 2016: Free Radical Biology & Medicine
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