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Babita Shashni, Yukio Nagasaki
The critical importance of reactive oxygen species (ROS) as oncogene activators and essential secondary messengers in cancer cell survival have been widely reported. Since oxidative stress has been implicated as being pivotal in various cancers, antioxidant therapy seems an apt strategy to abrogate ROS-mediated cellular processes to attenuate cancers. We therefore synthesized ROS scavenging nitroxide radical-containing nanoparticles (RNPs); pH insensitive RNPO and pH sensitive RNPN , to impede the proliferative and metastatic characteristics of the triple negative breast cancer cell line, MDA-MB-231, both in vitro and in vivo...
May 26, 2018: Biomaterials
Anita Matic, Ivana Jukic, Ana Stupin, Lidija Baric, Zrinka Mihaljevic, Sanela Unfirer, Ivana Tartaro Bujak, Branka Mihaljevic, Julian H Lombard, Ines Drenjancevic
The goal of this study was to examine the effect of 1-week of high salt (HS) intake and the role of oxidative stress in changing the mechanisms of flow-induced dilation (FID) in isolated pressurized middle cerebral arteries (MCA) of male Sprague-Dawley rats (N=15-16/per group). Reduced FID in the HS group was restored by intake of the superoxide scavenger TEMPOL (HS+TEMPOL in vivo group). Nitric oxide synthases (NOS) inhibitor Nω -nitro-L-arginine methyl ester (L-NAME), COX inhibitor indomethacin (INDO) and selective inhibitor of microsomal CYP450 epoxidase activity N-(methylsulfonyl)-2-(2-propynyloxy)-benzenehexanamide (MS-PPOH) significantly reduced FID in the LS group, while FID in the HS group was mediated by NO only...
June 15, 2018: American Journal of Physiology. Heart and Circulatory Physiology
Ellen E Gillis, Krystal N Brinson, Olga Rafikova, Wei Chen, Jacqueline B Musall, David G Harrison, Jennifer C Sullivan
We previously published that female spontaneously hypertensive rats (SHR) have significantly greater nitric oxide (NO) bioavailability and NO synthase (NOS) enzymatic activity in the renal inner medulla compared to age-matched males, although the mechanism responsible remains unknown.  Tetrahydrobiopterin (BH4 ) is a critical cofactor required for NO generation, and decreases in BH4 as the result of increases in oxidative stress have been implicated in the pathogenesis of hypertension.  As male SHR are known to have higher levels of oxidative stress compared to female SHR, we hypothesized that relative BH4 deficiency induced by oxidative stress in male SHR results in lower levels of NOS activity in renal inner medulla compared to females...
June 13, 2018: Bioscience Reports
Lei Hou, Junjie Guo, Feng Xu, Xinyu Weng, Wenhui Yue, Junbo Ge
Asymmetric dimethylarginine (ADMA) is a risk factor for heart diseases. Dimethylarginine dimethylaminohydrolase (DDAH) enzymes are key proteins for ADMA degradation. Endothelial DDAH1 is a vital regulator of angiogenesis. DDAH1 is also expressed in cardiomyocytes. However, the role of DDAH1 in cardiomyocytes needs further clarification. Herein, we used an inducible cardiac-specific DDAH1 knockdown mouse (cardiac DDAH1-/- ) to investigate the role of cardiomyocyte DDAH1 in left-ventricular (LV) remodeling after acute myocardial infarction (AMI)...
June 11, 2018: Basic Research in Cardiology
Gensheng Zhang, Qin Wang, Wenwen Wang, Minghua Yu, Suping Zhang, Nan Xu, Suhan Zhou, Xiaoyun Cao, Xiaodong Fu, Zufu Ma, Ruisheng Liu, Jianhua Mao, En Yin Lai
BACKGROUND/AIMS: Free radical scavenger tempol is a protective antioxidant against ischemic injury. Tubular epithelial apoptosis is one of the main changes in the renal ischemia/reperfusion (I/R) injury. Meanwhile some proteins related with apoptosis and inflammation are also involved in renal I/R injury. We tested the hypothesis that tempol protects against renal I/R injury by activating protein kinase B/mammalian target of rapamycin (PKB, Akt/mTOR) and glycogen synthase kinase 3β (GSK3β) pathways as well as the coordinating apoptosis and inflammation related proteins...
May 30, 2018: Kidney & Blood Pressure Research
Wasan Abdulmahdi, May M Rabadi, Edson Jules, Yara Marghani, Noor Marji, Jessica Leung, Frank Fan Zhang, Avi Siani, Tamar Siskind, Kiara Vedovino, Nazrul Chowdhury, Miroslav Sekulic, Brian B Ratliff
Maternal undernutrition during pregnancy leads to low birth weight (LBW) neonates that have a reduced kidney nephron endowment and higher morbidity as adults. Using a severe combined caloric and protein restricted mouse model of MUN to generate LBW mice, we examined the progression of renal insufficiency in LBW adults. Through 6 months of age, LBW males experienced greater albuminuria (ELISA analysis), a more rapid onset of glomerular hypertrophy and a worse survival rate than LBW females. In contrast, both genders experienced a comparable progressive decline in renal vascular density (immunofluorescence analysis), renal blood flow (Laser-Doppler flowmetry analysis), glomerular filtration rate (FITC-sinistrin clearance analysis), and a progressive increase in systemic blood pressure (measured via tail-cuff method)...
May 30, 2018: American Journal of Physiology. Renal Physiology
Bambang Setiohadji, Irawati Irfani, Maula Rifada, Rova Virgana, Arief S Kartasasmita
INTRODUCTION: The incidence of blindness due to methanol intoxication is higher in males of productive age. The management of methanol-induced toxic optic neuropathy is yet to produce satisfactory results. Antioxidant therapy is now used as an alternative method of preventing methanol intoxication. The aim of this study was to observe the effect of TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidinyl-1-oxyl), a superoxide dismutase (SOD) mimetic, on retinal ganglion cells in methanol-intoxicated rats...
May 24, 2018: Ophthalmology and Therapy
Filipe Martinuzo Filetti, Dalton Valentim Vassallo, Mirian Fioresi, Maylla Ronacher Simões
Copper is an essential metal for homeostasis and the functioning of living organisms. We investigated the effects of a high copper concentration on the myocardial mechanics, investigating the reactive oxygen species (ROS) mediated effects. The developed force of papillary muscles was reduced after acute exposure to a high copper concentration and was prevented by co-incubation with tempol, DMSO and catalase. The reuptake of calcium by the sarcoplasmic reticulum was reduced by copper and restored by tempol. The contractile response to Ca2+ was reduced and reversed by antioxidants...
May 14, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Pablo Llévenes, Gloria Balfagón, Javier Blanco-Rivero
We aimed to determine the influence of nitrergic innervation function on the decreased mesenteric arterial tone induced by high levels of triiodothyronine (T3), as a model of acute thyroiditis, as well as the mechanism/s implicated. We analysed in mesenteric segments from male Wistar rats the effect of 10 nmol/L T3 (2 h) on the vasomotor response to electrical field stimulation (EFS) in the presence/absence of specific neuronal NOS (nNOS) inhibitor L-NPA, or superoxide anion scavenger tempol. Nitric oxide (NO) release was measured in the presence/absence of tempol or PI3K inhibitor LY294002...
May 8, 2018: Vascular Pharmacology
Corbin A Shields, Maggie McCalmon, Tarek Ibrahim, Dakota L White, Jan Michael Williams, Babbette D LaMarca, Denise C Cornelius
Previous studies have demonstrated that T-helper 17 cells (TH 17s) and cytolytic NK cells (cNKs) are increased in women with preeclampsia (PE). In this study, we investigated the role of placental ischemia-stimulated TH 17s to induce cNKs in pregnancy. We further assessed the role of TH 17-mediated oxidative stress to facilitate cNK activation in pregnancy by treating with the SOD mimetic tempol. CD4+ /CD25- cells were isolated from reduced uterine perfusion pressure (RUPP) rats and differentiated into TH 17 cells in vitro...
May 2, 2018: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Tian-Zhi Guo, Tzuping Wei, Ting-Ting Huang, Wade S Kingery, John David Clark
Clinical evidence suggests vitamin C (Vit C) may protect against the development of complex regional pain syndrome (CRPS) after fracture and/or surgery. Tibia fracture followed by 4 weeks cast immobilization (fracture/cast) in rats results in nociceptive, vascular, and bone changes resembling clinical CRPS. In the present study, fracture/cast rats were treated with the oxidative stress inhibitors Vit C, N-acetyl cysteine (NAC) or 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPOL) to examine their effects on CRPS-related nociceptive and vascular changes...
April 28, 2018: Journal of Pain: Official Journal of the American Pain Society
Xi Chen, Wei-Bin Shen, Penghua Yang, Daoyin Dong, Winny Sun, Peixin Yang
Maternal diabetes induces neural tube defects by suppressing neurogenesis in the developing neuroepithelium. Our recent study further revealed that high glucose inhibited embryonic stem cell differentiation into neural lineage cells. However, the mechanism whereby high glucose suppresses neural differentiation is unclear. To investigate whether high glucose-induced oxidative stress and endoplasmic reticulum stress (ER stress) lead to the inhibition of neural differentiation, the effect of high glucose on neural stem cell (the C17...
April 26, 2018: Stem Cells and Development
Fangchao Xue, Yuquan Wang, Qixiong Zhang, Songling Han, Fuzhong Zhang, Taotao Jin, Chenwen Li, Houyuan Hu, Jianxiang Zhang
There has been increasing interest in constructing affinity-based drug delivery systems via different non-covalent interactions. Herein we report a host-guest interaction-based strategy to develop effective drug delivery systems using cyclodextrin-containing copolymers. Hydrophilic copolymers with one polyethylene glycol block and another block containing either α-cyclodextrin or β-cyclodextrin were synthesized. Using poly(β-benzyl l-aspartate) and pyrene as model guest compounds, we demonstrated the nanoparticle formation by host-guest interaction-mediated self-assembly...
April 23, 2018: Nanoscale
Rooban B Nahomi, Sruthi Sampathkumar, Angela M Myers, Lynda Elghazi, Dawn G Smith, Jie Tang, C Allen Lee, Timothy S Kern, Ram H Nagaraj, Patrice E Fort
Purpose: Loss of retinal capillary endothelial cells and pericytes through apoptosis is an early event in diabetic retinopathy (DR). Inflammatory pathways play a role in early DR, yet the biochemical mechanisms are poorly understood. In this study, we investigated the role of indoleamine 2,3-dioxygenase (IDO), an inflammatory cytokine-inducible enzyme, on retinal endothelial apoptosis and capillary degeneration in the diabetic retina. Methods: IDO was detected in human and mouse retinas by immunohistochemistry or Western blotting...
April 1, 2018: Investigative Ophthalmology & Visual Science
Shigefumi Morioka, Hirofumi Sakaguchi, Taro Yamaguchi, Yuzuru Ninoyu, Hiroaki Mohri, Takashi Nakamura, Yasuo Hisa, Kiyokazu Ogita, Naoaki Saito, Takehiko Ueyama
Previous studies have convincingly argued that reactive oxygen species (ROS) contribute to the development of several major types of sensorineural hearing loss, such as noise-induced hearing loss (NIHL), drug-induced hearing loss, and age-related hearing loss. However, the underlying molecular mechanisms induced by ROS in these pathologies remain unclear. To resolve this issue, we established an in vivo model of ROS overproduction by generating a transgenic (TG) mouse line expressing the human NADPH oxidase 4 (NOX4, NOX4-TG mice), which is a constitutively active ROS-producing enzyme that does not require stimulation or an activator...
April 20, 2018: Journal of Neurochemistry
Qian Wang, Xin Sui, Rui Chen, Peiyong Ma, Tao Ding, Dianjun Sui, Ping Yang
This study aims to investigate whether the molecular mechanisms by which Ghrelin inhibits cardiac fibrosis are linked to the NADPH oxidase-ROS signaling pathway. Adult male Sprague Dawley (SD) rats were randomly divided into 4 groups: sham, myocardial infarction (MI), MI + Ghrelin (100 μg/kg, twice daily, subcutaneous for 4 weeks beginning 24 h post-MI), or Ghrelin alone. Adult rat cardiac fibroblasts (CFs) were isolated and pretreated with or without Ghrelin for 24 h, followed by stimulation with or without angiotensin II (Ang II) for another 24 h...
April 17, 2018: Clinical and Experimental Pharmacology & Physiology
Hany M El-Bassossy, Thikryat Neamatallah, Khadijah S Balamash, Amani T Abushareb, Malcolm L Watson
BACKGROUND: Advanced glycation endproducts (AGEs) play a major role in the development of many vascular complications that are mediated by endothelial dysfunction. The present work aimed to investigate the mechanism by which AGEs impair vasodilation. METHODS: The effect of AGEs on vasodilation induced by acetylcholine or D NONOate was examined by incubating isolated rat aortae with different AGEs concentrations. ACh-induced nitric oxide generation was assessed using the fluorescent probe diaminofluorecein (DAF-FM)...
May 23, 2018: Biochemical and Biophysical Research Communications
Hitesh Soni, Damian Kaminski, Rajashekhar Gangaraju, Adebowale Adebiyi
Acute kidney injury (AKI), a significant complication of cisplatin chemotherapy is associated with reactive oxygen species (ROS)-dependent renal cell death, but the cellular targets of ROS in cisplatin nephrotoxicity are not fully resolved. Here, we investigated cisplatin-induced oxidative renal damage and tested the hypothesis that ROS-dependent shedding of death activator Fas ligand (FasL) occurs in cisplatin nephropathy. We show that intraperitoneal injection of sulfobutyl ether-β-cyclodextrin (Captisol™)-solubilized cisplatin elevated the level of lipid peroxidation product malondialdehyde in mouse kidneys and urinary concentration of oxidative DNA damage biomarker 8-hydroxy-2'-deoxyguanosine...
November 2018: Renal Failure
Kristy L Jackson, Francine Z Marques, Kyungjoon Lim, Pamela J Davern, Geoffrey A Head
Objective: Genetically hypertensive BPH/2J mice are recognized as a neurogenic model of hypertension, primarily based on sympathetic overactivity and greater neuronal activity in cardiovascular regulatory brain regions. Greater activity of the central renin angiotensin system (RAS) and reactive oxygen species (ROS) reportedly contribute to other models of hypertension. Importantly the peripheral RAS contributes to the hypertension in BPH/2J mice, predominantly during the dark period of the 24 h light cycle...
2018: Frontiers in Physiology
Zhengmeng Ye, Xi Lu, Yi Deng, Xinquan Wang, Shuo Zheng, Hongmei Ren, Miao Zhang, Tingting Chen, Pedro A Jose, Jian Yang, Chunyu Zeng
BACKGROUND/AIMS: Adverse environment in utero can modulate adult phenotypes including blood pressure. Fine particulate matter (PM2.5) exposure in utero causes hypertension in the offspring, but the exact mechanisms are not clear. Renal dopamine D1 receptor (D1R), regulated by G protein-coupled receptor kinase type 4 (GRK4), plays an important role in the regulation of renal sodium transport and blood pressure. In this present study, we determined if renal D1R dysfunction is involved in PM2...
2018: Cellular Physiology and Biochemistry
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