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TEMPOL

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https://www.readbyqxmd.com/read/29025747/uncoupling-protein-2-inhibits-myointimal-hyperplasia-in-preclinical-animal-models-of-vascular-injury
#1
Yan Zhang, Yaolei Zhang, Wei Li, Peijian Wang, Rui Gu, Yaxing Feng, Shujie Wei, Ke Peng, Yunrong Zhang, Linan Su, Qiang Wang, De Li, Dachun Yang, Wing Tak Wong, Yongjian Yang, Shuangtao Ma
BACKGROUND: Intracoronary stent restenosis, characterized by excessive smooth muscle cell (SMC) proliferation and myointimal hyperplasia, remains a clinical challenge. Mitochondrial membrane potential has been linked to the proliferative rate of SMCs. This study aimed to screen a critical gene regulating mitochondrial potential and to confirm its effects on myointimal formation in preclinical animal models. METHODS AND RESULTS: We performed transcriptome screening for genes differentially expressed in ligated versus unligated mouse carotid arteries...
October 12, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28938336/arterial-stiffness-induced-by-carotid-calcification-leads-to-cerebral-gliosis-mediated-by-oxidative-stress
#2
Nataliya Sadekova, M Florencia Iulita, Diane Vallerand, Gervais Muhire, Mohamed Bourmoum, Audrey Claing, Hélène Girouard
BACKGROUND: Arterial stiffness is a risk factor for cognitive decline and dementia. However, its precise effects on the brain remain unexplored. Using a mouse model of carotid stiffness, we investigated its effect on glial activation and oxidative stress. METHODS: Arterial stiffness was induced by the application of calcium chloride to the adventitial region of the right carotid. Superoxide anion production, NADPH activity and levels, as well as glial activation were examined with immunohistochemical and biochemical approaches, 2-week postcalcification...
September 21, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28925291/isolation-of-a-novel-compound-mimo2-from-the-methanolic-extract-of-moringa-oleifera-leaves-protective-effects-against-vanadium-induced-cytotoxity
#3
Olumayowa O Igado, Jan Glaser, Mario Ramos-Tirado, Ezgi Eylül Bankoğlu, Foluso A Atiba, Ulrike Holzgrabe, Helga Stopper, James O Olopade
Moringa oleifera is reported to be a miracle plant, with positive effects on practically every system in the animal body. The methanolic extract of Moringa oleifera leaves was fractionated using liquid-liquid fractionation, column chromatography and preparative high-performance liquid chromatography (HPLC). Bioassay guided fractionation using Ferric Reducing Antioxidant Power (FRAP) was used to determine the fraction with the highest antioxidative power. Chemical structure was elucidated with nuclear magnetic resonance (NMR) spectroscopy...
September 19, 2017: Drug and Chemical Toxicology
https://www.readbyqxmd.com/read/28894248/chronic-treatment-with-tempol-during-acquisition-or-withdrawal-from-cpp-abolishes-the-expression-of-cocaine-reward-and-diminishes-oxidative-damage
#4
Tehila Beiser, Ran Numa, Ron Kohen, Rami Yaka
In previous studies, we reported that pretreatment with the antioxidant Tempol attenuated the development and expression of cocaine-induced psychomotor sensitization in rats and diminished cocaine-induced oxidative stress (OS) in the prefrontal cortex (PFC) and nucleus accumbens (NAc), suggesting a potential role for Tempol in interfering with cocaine-related psychomotor sensitization. The aim of the current study was to examine the role of Tempol in reward and reinforcement using the conditioned place preference (CPP) paradigm...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28890952/oxidative-stress-a-potential-therapeutic-target-in-placental-malaria
#5
Demba Sarr, Caitlin A Cooper, Tara C Bracken, Omar Martinez-Uribe, Tamas Nagy, Julie M Moore
Placental malaria, characterized by sequestration of Plasmodium falciparum in the maternal placental blood space and associated inflammatory damage, contributes to poor birth outcomes and ~200,000 infant deaths annually. Specific mechanisms that contribute to placental damage and dysfunction during malaria are not completely understood. To investigate a potential role for oxidative stress, antioxidant genes and markers for oxidative damage were assessed by quantitative PCR and immunohistochemistry in Plasmodium chabaudi AS-infected pregnant mice...
June 1, 2017: Immunohorizons
https://www.readbyqxmd.com/read/28842207/central-administration-of-tert-butylhydroquinone-attenuates-hypertension-via-regulating-nrf2-signaling-in-the-hypothalamic-paraventricular-nucleus-of-hypertensive-rats
#6
Juan Bai, Xiao-Jing Yu, Kai-Li Liu, Fang-Fang Wang, Gui-Xia Jing, Hong-Bao Li, Yan Zhang, Chan-Juan Huo, Xiang Li, Hong-Li Gao, Jie Qi, Yu-Ming Kang
Reactive oxygen species (ROS) in the paraventricular nucleus (PVN) play a pivotal role in the pathogenesis of hypertension. Nuclear factor E2-related factor-2 (Nrf2) is an important transcription factor that modulates cell antioxidant defense response against oxidative stress. The present study aimed to explore the efficacy of PVN administration of tert-butylhydroquinone (tBHQ), a selective Nrf2 activator, in hypertensive rats. 16-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were used in this study...
October 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28826937/tempol-improves-lipid-profile-and-prevents-left-ventricular-hypertrophy-in-ldl-receptor-gene-knockout-ldlr-mice-on-a-high-fat-diet
#7
Igor Cândido Viana Gonçalves, Cláudio Daniel Cerdeira, Eduardo Poletti Camara, José Antônio Dias Garcia, Maísa Ribeiro Pereira Lima Brigagão, Roberta Bessa Veloso Silva, Gérsika Bitencourt Dos Santos
INTRODUCTION AND OBJECTIVE: Dyslipidemia is associated with increased risk of cardiovascular disease and atherosclerosis, and hence with high morbidity and mortality. This study investigated the effects of the nitroxide 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (Tempol) on lipid profile and cardiac morphology in low-density lipoprotein (LDL) receptor gene knockout (LDLr-/-) mice. METHODS: Male LDLr-/- mice (three months old, approximately 22 g weight) were divided into the following groups: controls, including (1) standard chow (SC, n=8) and (2) high-fat diet (HFD, n=8); and treatment, including (3) standard chow + Tempol (SC+T, n=8) (30 mg/kg administered by gavage, once daily) and (4) high-fat diet + Tempol (HFD+T, n=8) (30 mg/kg)...
August 18, 2017: Portuguese Journal of Cardiology: An Official Journal of the Portuguese Society of Cardiology
https://www.readbyqxmd.com/read/28754499/fructose-induced-neurogenic-hypertension-mediated-by-overactivation-of-p38-mapk-to-impair-insulin-signaling-transduction-caused-central-insulin-resistance
#8
Pei-Wen Cheng, Yu-Te Lin, Wen-Yu Ho, Pei-Jung Lu, Hsin-Hung Chen, Chi-Cheng Lai, Gwo-Ching Sun, Tung-Chen Yeh, Michael Hsiao, Ching-Jiunn Tseng, Chun-Peng Liu
Type 2 diabetes are at a high risk of complications related to hypertension, and reports have indicated that insulin levels may be associated with blood pressure (BP). Fructose intake has recently been reported to promote insulin resistance and superoxide formation. The aim of this study is to investigate whether fructose intake can enhance superoxide generation and impair insulin signaling in the NTS and subsequently elevate BP in rats with fructose-induced hypertension. Treatment with fructose for 4 weeks increased the BP, serum fasting insulin, glucose, homeostatic model assessment-insulin resistance, and triglyceride levels and reduced the serum direct high-density lipoprotein level in the fructose group...
July 25, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28750563/high-dose-ascorbic-acid-induces-carcinostatic-effects-through-hydrogen-peroxide-and-superoxide-anion-radical-generation-induced-cell-death-and-growth-arrest-in-human-tongue-carcinoma-cells
#9
Ryouhei Ohwada, Yu Ozeki, Yasukazu Saitoh
High-dose ascorbic acid (AsA) treatment, known as pharmacological AsA, has been shown to exert carcinostatic effects in many types of cancer cells and in vivo tumour models. Although pharmacological AsA has potential as a complementary and alternative medicine for anticancer treatment, its effects on human tongue carcinoma have not yet been elucidated. In this study, we investigated the effect of AsA treatment on human tongue carcinoma HSC-4 cells compared with non-tumourigenic tongue epithelial dysplastic oral keratinocyte (DOK) cells...
July 2017: Free Radical Research
https://www.readbyqxmd.com/read/28712765/losartan-reverses-cox-2-dependent-vascular-dysfunction-in-offspring-of-hyperglycaemic-rats
#10
Diego Barbosa de Queiroz, Fernanda Elizabethe Ramos-Alves, Juliana Santos-Rocha, Gloria Pinto Duarte, Fabiano Elias Xavier
AIMS: This study examined whether chronic treatment with losartan, an angiotensin II type 1 receptor (AT1R) antagonist, might reverse COX-2-mediated vascular dysfunction in mesenteric resistance arteries (MRA) from offspring of hyperglycaemic rats. MATERIALS AND METHODS: Male 12-month-old offspring of hyperglycaemic (O-DR) and normoglycaemic (O-CR) rats were treated with losartan (15mg·kg·day(-1)) during 2months. Third order MRA of untreated and losartan-treated O-DR and O-CR were mounted in wire myograph for isometric tension measurements...
September 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/28684629/genetic-deletion-of-nadph-oxidase-1-rescues-microvascular-function-in-mice-with-metabolic-disease
#11
Jennifer A Thompson, Sebastian Larion, James D Mintz, Eric J Belin de Chantemèle, David J Fulton, David W Stepp
RATIONALE: Early vascular changes in metabolic disease that precipitate the development of cardiovascular complications are largely driven by reactive oxygen species accumulation, yet the extent to which excess reactive oxygen species derive from specific NADPH oxidase isoforms remains ill defined. OBJECTIVE: Identify the role of Nox1 in the development of microvascular dysfunction in metabolic disease. METHODS AND RESULTS: Four genotypes were generated by breeding Nox1 knockout mice with db/db mice: lean (HdbWnox1), lean Nox1 knockout (HdbKnox1), obese (KdbWnox1), and obese KK (KdbKnox1)...
August 18, 2017: Circulation Research
https://www.readbyqxmd.com/read/28674038/genetic-interference-with-endothelial-ppar-%C3%AE-peroxisome-proliferator-activated-receptor-%C3%AE-augments-effects-of-angiotensin-ii-while-impairing-responses-to-angiotensin-1-7
#12
T Michael De Silva, Chunyan Hu, Dale A Kinzenbaw, Mary L Modrick, Curt D Sigmund, Frank M Faraci
Pharmacological activation of PPAR-γ (peroxisome proliferator-activated receptor-γ) protects the vasculature. Much less is known on the cell-specific impact of PPAR-γ when driven by endogenous ligands. Recently, we found that endothelial PPAR-γ protects against angiotensin II-induced endothelial dysfunction. Here, we explored that concept further examining whether effects were sex dependent along with underlying mechanisms. We studied mice expressing a human dominant-negative mutation in PPAR-γ driven by the endothelial-specific vascular cadherin promoter (E-V290M), using nontransgenic littermates as controls...
September 2017: Hypertension
https://www.readbyqxmd.com/read/28673614/ros-dependent-activation-of-rhoa-rho-kinase-in-pulmonary-artery-role-of-src-family-kinases-and-arhgef1
#13
Charles E MacKay, Yasin Shaifta, Vladimir V Snetkov, Asvi A Francois, Jeremy P T Ward, Greg A Knock
The role of reactive oxygen species (ROS) in smooth muscle contraction is poorly understood. We hypothesised that G-protein coupled receptor (GPCR) activation and hypoxia induce Rho-kinase activity and contraction in rat intra-pulmonary artery (IPA) via stimulation of ROS production and subsequent Src-family kinase (SrcFK) activation. The T-type prostanoid receptor agonist U46619 induced ROS production in pulmonary artery smooth muscle cells (PASMC). U46619 also induced c-Src cysteine oxidation, SrcFK auto-phosphorylation, MYPT-1 and MLC20 phosphorylation and contraction in IPA, and all these responses were inhibited by antioxidants (ebselen, Tempol)...
September 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28666030/contribution-of-reactive-oxygen-species-to-the-pathogenesis-of-pulmonary-arterial-hypertension
#14
Nikki L Jernigan, Jay S Naik, Laura Weise-Cross, Neil D Detweiler, Lindsay M Herbert, Tracylyn R Yellowhair, Thomas C Resta
Pulmonary arterial hypertension is associated with a decreased antioxidant capacity. However, neither the contribution of reactive oxygen species to pulmonary vasoconstrictor sensitivity, nor the therapeutic efficacy of antioxidant strategies in this setting are known. We hypothesized that reactive oxygen species play a central role in mediating both vasoconstrictor and arterial remodeling components of severe pulmonary arterial hypertension. We examined the effect of the chemical antioxidant, TEMPOL, on right ventricular systolic pressure, vascular remodeling, and enhanced vasoconstrictor reactivity in both chronic hypoxia and hypoxia/SU5416 rat models of pulmonary hypertension...
2017: PloS One
https://www.readbyqxmd.com/read/28659507/pressor-response-to-angiotensin-ii-is-enhanced-in-aged-mice-and-associated-with-inflammation-vasoconstriction-and-oxidative-stress
#15
Quynh Nhu Dinh, Grant R Drummond, Barbara K Kemp-Harper, Henry Diep, T Michael De Silva, Hyun Ah Kim, Antony Vinh, Avril A B Robertson, Matthew A Cooper, Ashley Mansell, Sophocles Chrissobolis, Christopher G Sobey
Aging is commonly associated with chronic low-grade inflammation and hypertension but it is unknown whether a cause-effect relationship exists between them. We compared the sensitivity of young adult (8-12 w) and aged (23-31 mo) male C57Bl6J mice to develop hypertension in response to a slow-pressor dose of angiotensin II (Ang II; 0.28 mg/kg/d; 28 d). In young mice, the pressor response to Ang II was gradual and increased to 142±8 mmHg over 28 d. However, in aged mice, Ang II promptly increased SBP and reached 155±12 mmHg by 28 d...
June 28, 2017: Aging
https://www.readbyqxmd.com/read/28655717/deletion-of-ucp1-enhances-ex-vivo-aortic-vasomotor-function-in-female-but-not-male-mice-despite-similar-susceptibility-to-metabolic-dysfunction
#16
Nathan C Winn, Zachary I Grunewald, Michelle L Gastecki, Makenzie L Woodford, Rebecca J Welly, Stephanie L Clookey, James R Ball, T'Keaya L Gaines, Natalia G Karasseva, Jill A Kanaley, Harold S Sacks, Victoria J Vieira-Potter, Jaume Padilla
Females are typically more insulin sensitive than males, which may be partly attributed to greater brown adipose tissue (BAT) activity and uncoupling protein 1 (UCP1) content. Accordingly, we tested the hypothesis that UCP1 deletion would abolish sex differences in insulin sensitivity and that whitening of thoracic periaortic BAT caused by UCP1 loss would be accompanied with impaired thoracic aortic function. Furthermore, because UCP1 exerts antioxidant effects, we examined whether UCP1 deficiency-induced metabolic dysfunction was mediated by oxidative stress...
October 1, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28633109/endothelial-nlrp3-inflammasome-activation-and-arterial-neointima-formation-associated-with-acid-sphingomyelinase-during-hypercholesterolemia
#17
Saisudha Koka, Min Xia, Yang Chen, Owais M Bhat, Xinxu Yuan, Krishna M Boini, Pin-Lan Li
The NLRP3 inflammasome has been reported to be activated by atherogenic factors, whereby endothelial injury and consequent atherosclerotic lesions are triggered in the arterial wall. However, the mechanisms activating and regulating NLRP3 inflammasomes remain poorly understood. The present study tested whether acid sphingomyelinase (ASM) and ceramide associated membrane raft (MR) signaling platforms contribute to the activation of NLRP3 inflammasomes and atherosclerotic lesions during hypercholesterolemia. We found that 7-ketocholesterol (7-Keto) or cholesterol crystal (ChC) markedly increased the formation and activation of NLRP3 inflammasomes in mouse carotid arterial endothelial cells (CAECs), as shown by increased colocalization of NLRP3 with ASC or caspase-1, enhanced caspase-1 activity and elevated IL-1β levels, which were markedly attenuated by mouse Asm siRNA, ASM inhibitor- amitriptyline, and deletion of mouse Asm gene...
June 15, 2017: Redox Biology
https://www.readbyqxmd.com/read/28630313/targeting-reactive-nitrogen-species-suppresses-hereditary-pancreatic-cancer
#18
Mo Li, Qian Chen, Teng Ma, Xiaochun Yu
Germline mutation of BRCA2 induces hereditary pancreatic cancer. However, how BRCA2 mutation specifically induces pancreatic tumorigenesis remains elusive. Here, we have examined a mouse model of Brca2-deficiency-induced pancreatic tumors and found that excessive reactive nitrogen species (RNS), such as nitrite, are generated in precancerous pancreases, which induce massive DNA damage, including DNA double-strand breaks. RNS-induced DNA lesions cause genomic instability in the absence of Brca2. Moreover, with the treatment of antioxidant tempol to suppress RNS, not only are DNA lesions significantly reduced, but also the onset of pancreatic cancer is delayed...
July 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28626074/a-type-k-channels-contribute-to-the-prorenin-increase-of-firing-activity-in-hypothalamic-vasopressin-neurosecretory-neurons
#19
Soledad Pitra, Javier E Stern
Recent studies have supported an important contribution of prorenin (PR) and its receptor (PRR) to the regulation of hypothalamic, sympathetic, and neurosecretory outflows to the cardiovascular system, including systemic release of vasopressin (VP), both under physiological and cardiovascular disease conditions. Still, the identification of precise cellular mechanisms and neuronal/molecular targets remain unknown. We have recently shown that PRR is expressed in VP neurons and that their activation increases neuronal activity...
September 1, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28603016/rapid-repeatable-in%C3%A2-vivo-detection-of-retinal-reactive-oxygen-species
#20
Ning Fan, Sean M Silverman, Yang Liu, Xizhen Wang, Byung-Jin Kim, Liping Tang, Abbot F Clark, Xuyang Liu, Iok-Hou Pang
Oxidative injuries, such as those related to reactive oxygen species (ROS), have been implicated in various retinal and optic nerve disorders. Many ROS detection methods have been developed. Although widely utilized, many of these methods are useful only in post mortem tissues, or require relatively expensive equipment, or involve intraocular injection. In the present study, we demonstrated and characterized a chemiluminescent probe L-012 as a noninvasive, in vivo ROS detection agent in the mouse retina. Using optic nerve crush (ONC) and retinal ischemia/reperfusion (I/R) as injury models, we show that L-012 produced intensive luminescent signals specifically in the injured eyes...
August 2017: Experimental Eye Research
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