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SOD AND tempol

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
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
Kathleen M Lukaszewicz, Mahesh P Paudyal, John R Falck, Julian H Lombard
OBJECTIVE: The potential contribution of CYP4A enzymes to endothelial dysfunction in Dahl salt-sensitive (SS) rats was determined by comparison to SS-5(BN) consomic rats having chromosome 5 carrying CYP4A alleles from the Brown Norway (BN) rat introgressed into the SS genetic background. METHODS: The following experiments were performed in cerebral arteries from HS-fed SS and SS-5(BN) rats ± the SOD inhibitor DETC and/or the superoxide scavenger Tempol: 1) endothelial function was determined via video microscopy ± acute addition of the CYP4A inhibitor DDMS or Tempol; 2) vascular oxidative stress was assessed with DHE fluorescence ± acute addition of DDMS, L-NAME, or PEG-SOD; and 3) CYP4A protein levels were compared by Western blotting...
August 18, 2016: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
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
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
Peng Jin, Tao Li, Xueqi Li, Xinghua Shen, Yanru Zhao
Myocardial infarction is a major contributor to morbidity and mortality in diabetes, which is characterized by inadequate angiogenesis and consequent poor blood reperfusion in the diabetic ischemic heart. The aim of the present study was to investigate the effect that oxidative stress in endothelial progenitor cells (EPCs) has on cardiac angiogenesis in diabetic mice. EPCs derived from diabetic mice revealed reductions in superoxide dismutase (SOD) expression levels and activity compared with those from normal mice...
June 2016: Experimental and Therapeutic Medicine
Yusi Wang, Paramita Pati, Yiming Xu, Feng Chen, David W Stepp, Yuqing Huo, R Daniel Rudic, David J R Fulton
The circadian clock is a transcriptional network that functions to regulate the expression of genes important in the anticipation of changes in cellular and organ function. Recent studies have revealed that the recognition of pathogens and subsequent initiation of inflammatory responses are strongly regulated by a macrophage-intrinsic circadian clock. We hypothesized that the circadian pattern of gene expression might be influenced by inflammatory stimuli and that loss of circadian function in immune cells can promote pro-inflammatory behavior...
2016: PloS One
Ankita Salvi, Gaurav Patki, Eisha Khan, Mohammad Asghar, Samina Salim
Using a simulated oxidative stress model of hippocampus-derived immortalized cell line (HT22), we report that prooxidant buthionine sulfoximine (BSO, 1 mM, 14 h), without adversely affecting cell viability or morphology, induced oxidative stress by inhibiting glutathione synthesis. BSO treatment also significantly reduced superoxide dismutase (SOD) activity (p < 0.05) and significantly lowered total antioxidant capacity (p < 0.001) in HT22 cells when compared to vehicle treated control cells. Antioxidant tempol, a piperidine nitroxide considered a SOD mimetic, reversed BSO-induced decline in SOD activity (p < 0...
2016: Oxidative Medicine and Cellular Longevity
Alessandra A Gallina, Anna Palumbo, Raffaella Casotti
Polyunsaturated aldehydes (PUA) have recently been shown to induce reactive oxygen species (ROS) and possibly reactive nitrogen species (RNS, e.g., peroxynitrite) in the diatom Skeletonema marinoi (S. marinoi), which produces high amounts of PUA. We now are attempting to acquire better understanding of which reactive molecular species are involved in the oxidative response of S. marinoi to PUA. We used flow cytometry, the dye dihydrorhodamine 123 (DHR) as the main indicator of ROS (but which is also known to partially detect RNS), and different scavengers and inhibitors of both nitric oxide (NO) synthesis and superoxide dismutase activity (SOD)...
August 2016: Journal of Phycology
Anita Cosic, Ivana Jukic, Ana Stupin, Martina Mihalj, Zrinka Mihaljevic, Sanja Novak, Rosemary Vukovic, Ines Drenjancevic
KEY POINTS: Recent studies have shown that high salt (HS) intake leads to endothelial dysfunction and impaired vascular reactivity in different vascular beds in both animal and human models, due to increased oxidative stress. The objective of this study was to assess vascular response to flow-induced dilatation (FID) and to elucidate the role of vascular oxidative stress/antioxidative capacity in middle cerebral arteries (MCAs) of HS-fed rats in vitro. The novelty of this study is in demonstrating impaired flow-induced dilatation of MCAs and down-regulation of vascular antioxidant genes with HS intake, leading to increased levels of oxidative stress in blood vessels and peripheral lymph organs, which together contribute to impaired FID...
September 1, 2016: Journal of Physiology
Mohammed Ragab Abdel-Aziz Ali, Amira Morad Hussein Abo-Youssef, Basim Anwar Shehata Messiha, Mahmoud Mohamed Khattab
We aim to evaluate the protective role of the central angiotensin-converting enzyme (ACE) inhibitor perindopril, compared with the standard reactive oxygen species (ROS) scavenger tempol, against lipopolysaccharide (LPS)-induced cognition impairment and amyloidogenesis in a simulation to Alzheimer's disease (AD). Mice were allocated into a control group, an LPS control group (0.8 mg/kg, i.p., once), a tempol (100 mg/kg/day, p.o., 7 days) treatment group, and two perindopril (0.5 and 1 mg/kg/day, p.o., 7 days) treatment groups...
June 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
Jingwen Yu, Yanqing Wu, Peixin Yang
Aberrant epigenetic modifications are implicated in maternal diabetes-induced neural tube defects (NTDs). Because cellular stress plays a causal role in diabetic embryopathy, we investigated the possible role of the stress-resistant sirtuin (SIRT) family histone deacetylases. Among the seven sirtuins (SIRT1-7), pre-gestational maternal diabetes in vivo or high glucose in vitro significantly reduced the expression of SIRT 2 and SIRT6 in the embryo or neural stem cells, respectively. The down-regulation of SIRT2 and SIRT6 was reversed by superoxide dismutase 1 (SOD1) over-expression in the in vivo mouse model of diabetic embryopathy and the SOD mimetic, tempol and cell permeable SOD, PEGSOD in neural stem cell cultures...
May 2016: Journal of Neurochemistry
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
Xiaolin Zhu, Qinqin Gao, Qing Tu, Yuan Zhong, Di Zhu, Caiping Mao, Zhice Xu
Toxic factors could cause in utero hypoxia, and prenatal hypoxia (PH) increased incidence of cardiovascular diseases in late life. It is unclear whether/how PH causes vascular injury during fetal life. This study found that PH significantly increased angiotensin II (Ang II)-mediated vessel contractions in fetal thoracic aortas, which was blocked by losartan, not PD123319, indicating that AT1 receptors played a dominant role in the enhanced fetal vasoconstriction following hypoxia. Prenatal hypoxia increased superoxide production and decreased superoxide dismutase (SOD) expression, associated with the enhanced NADPH oxidase (Nox) 4, but not Nox1 or Nox2 in fetal aortas...
April 2016: Reproductive Toxicology
Hariane Côco, Larissa Pernomian, Katia C Marchi, Mayara S Gomes, Cláudia R de Andrade, Leandra N Z Ramalho, Carlos R Tirapelli, Ana M de Oliveira
OBJECTIVES: Our main objective was to investigate the mechanisms underlying the effects of hyperhomocysteinaemia (HHcy) on contractile response mediated by α1-adrenoceptors in the rat corpus cavernosum. METHODS: Concentration-response curves for phenylephrine (PE) were obtained in strips of corpus cavernosum, in absence or after incubation with tiron, tempol or polyethylene glycol (PEG)-catalase combined or not with tempol. We also measured the superoxide anion (O2(-)) and hydrogen peroxide (H2O2) generation, superoxide dismutase (SOD) and catalase activity and α-actin expression in rat corpus cavernosum from both groups...
January 2016: Journal of Pharmacy and Pharmacology
J A Troiano, S R Potje, M E Graton, P Cavalari, A A F Pereira, G T Vale, A C M S Nakamune, D H Sumida, C R Tirapelli, C Antoniali
AIMS: We determined whether decreased reactive oxygen species (ROS) production in the aorta of pregnant spontaneously hypertensive rats (SHR) resulted in increased nitric oxide (NO) bioavailability and hyporeactivity to phenylephrine (PE). MAIN METHODS: Systemic and aortic oxidative stress were measured in pregnant and non-pregnant Wistar rats and SHR. Furthermore, the hypotensive effects of apocynin (30 mg/kg) and Tempol (30 mg/kg) were analyzed. Intact aortic rings of pregnant and non-pregnant rats were stimulated with PE in the absence of or after incubation (30 min) with apocynin (100 μmol/L)...
January 1, 2016: Life Sciences
Jorge Camargo Oishi, Tereza Cristina Buzinnari, Cezar Rangel Pestana, Thiago Francisco De Moraes, Izabela Pereira Vatanabe, David Anderson Wink, Roberto Santana da Silva, Lusiane Maria Bendhack, Gerson Jhonatan Rodrigues
PURPOSE: The ruthenium complex cis-[Ru(H-dcbpy-)2(Cl)(NO)] (DCBPY) is a nitric oxide (NO) donor and studies suggested that the ruthenium compounds can inactivate O2-. The aim of this study is to test if DCBPY can revert and/or prevent the endothelial dysfunction. METHODS: Normotensive (2K) and hypertensive (2K-1C) wistar rats were used. To vascular reactivity study, thoracic aortas were isolated, rings with intact endothelium were incubated with: DCBPY: 0.1; 1 and 10μM, DCBPY plus hydroxocobalin (NO scavenger) or tempol during 30 minutes, and concentration effect curves to acetylcholine were performed...
2015: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
Karem H Alzoubi, Omar F Khabour, Amal S Albawaana, Farah H Alhashimi, Rabaa Y Athamneh
Sleep deprivation is associated with oxidative stress that causes learning and memory impairment. Tempol is a nitroxide compound that promotes the metabolism of many reactive oxygen species (ROS) and has antioxidant and neuroprotective effect. The current study investigated whether chronic administration of tempol can overcome oxidative stress and prevent learning and memory impairment induced by sleep deprivation. Sleep deprivation was induced in rats using multiple platform model. Tempol was administered to rats via oral gavages...
January 2016: Brain Research Bulletin
Jing Wu, Mohamed A Saleh, Annet Kirabo, Hana A Itani, Kim Ramil C Montaniel, Liang Xiao, Wei Chen, Raymond L Mernaugh, Hua Cai, Kenneth E Bernstein, Jörg J Goronzy, Cornelia M Weyand, John A Curci, Natalia R Barbaro, Heitor Moreno, Sean S Davies, L Jackson Roberts, Meena S Madhur, David G Harrison
Vascular oxidative injury accompanies many common conditions associated with hypertension. In the present study, we employed mouse models with excessive vascular production of ROS (tg(sm/p22phox) mice, which overexpress the NADPH oxidase subunit p22(phox) in smooth muscle, and mice with vascular-specific deletion of extracellular SOD) and have shown that these animals develop vascular collagen deposition, aortic stiffening, renal dysfunction, and hypertension with age. T cells from tg(sm/p22phox) mice produced high levels of IL-17A and IFN-γ...
January 2016: Journal of Clinical Investigation
Masashi Mukohda, Madeliene Stump, Pimonrat Ketsawatsomkron, Chunyan Hu, Frederick W Quelle, Curt D Sigmund
Loss of peroxisome proliferator-activated receptor (PPAR)-γ function in the vascular endothelium enhances atherosclerosis and NF-κB target gene expression in high-fat diet-fed apolipoprotein E-deficient mice. The mechanisms by which endothelial PPAR-γ regulates inflammatory responses and protects against atherosclerosis remain unclear. To assess functional interactions between PPAR-γ and inflammation, we used a model of IL-1β-induced aortic dysfunction in transgenic mice with endothelium-specific overexpression of either wild-type (E-WT) or dominant negative PPAR-γ (E-V290M)...
January 1, 2016: American Journal of Physiology. Heart and Circulatory Physiology
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