scholarly journals Benzbromarone Attenuates Oxidative Stress in Angiotensin II- and Salt-Induced Hypertensive Model Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Nanako Muraya ◽  
Daisuke Kadowaki ◽  
Shigeyuki Miyamura ◽  
Kenichiro Kitamura ◽  
Kohei Uchimura ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Angiotensin Ii ◽  
Radical Scavenging ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Scavenging Effect ◽  
Stress Markers ◽  
Radical Scavenging Effect

Oxidative stress induced by hyperuricemia is closely associated with the renin-angiotensin system, as well as the onset and progression of cardiovascular disease (CVD) and chronic kidney disease (CKD). It is therefore important to reduce oxidative stress to treat hyperuricemia. We previously found that benzbromarone, a uricosuric agent, has a direct free radical scavenging effect in vitro. The antioxidant effects of benzbromarone were evaluated in vivo via oral administration of benzbromarone for 4 weeks to model rats with angiotensin II- and salt-induced hypertension. Benzbromarone did not alter plasma uric acid levels or blood pressure but significantly reduced the levels of advanced oxidation protein products, which are oxidative stress markers. Furthermore, dihydroethidium staining of the kidney revealed a reduction in oxidative stress after benzbromarone administration. These results suggest that benzbromarone has a direct antioxidant effect in vivo and great potential to prevent CVD and CKD.

Role of angiotensin II in endothelial dysfunction induced by lipopolysaccharide in mice

2007 ◽  
Vol 293 (6) ◽  
pp. H3726-H3731 ◽  
Author(s):  
Donald D. Lund ◽  
Robert M. Brooks ◽  
Frank M. Faraci ◽  
Donald D. Heistad
Keyword(s):  
Oxidative Stress ◽  
Angiotensin Ii ◽  
Endothelial Dysfunction ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Disease States ◽  
Vasomotor Function

Endotoxin [or lipopolysaccharide (LPS)] increases levels of superoxide in blood vessels and impairs vasomotor function. Angiotensin II plays an important role in the generation of superoxide in several disease states, including hypertension and heart failure. The goal of this study was to determine whether the activation of the renin-angiotensin system contributes to oxidative stress and endothelial dysfunction after endotoxin. We examined the effects of enalapril (an angiotensin-converting enzyme inhibitor) or L-158809 (an angiotensin receptor blocker) on increases of superoxide and vasomotor dysfunction in mice treated with LPS. C57BL/6 mice were treated with either enalapril (60 mg·kg−1·day−1) or L-158809 (30 mg·kg−1·day−1) for 4 days. After the third day, LPS (10–20 mg/kg) or vehicle was injected intraperitoneally, and one day later, vasomotor function of the aorta was examined in vitro. After precontraction with PGF2α, the maximal responses to sodium nitroprusside were similar in the aorta from normal and LPS-treated mice. In contrast, the relaxation to acetylcholine was impaired after LPS (54 ± 5% at 10−5, mean ± SE) compared with vessels treated with vehicle (88 ± 1%; P < 0.05). Enalapril improved ( P < 0.05) relaxation in response to acetylcholine to 81 ± 6% after LPS. L-158809 also improved relaxation in response to acetylcholine to 77 ± 4% after LPS. Superoxide (measured with lucigenin and hydroethidine) was increased ( P < 0.05) in aorta after LPS, and levels were reduced ( P < 0.05) following enalapril and L-158809. Thus, after LPS, enalapril and L-158809 reduce superoxide levels and improve relaxation to acetylcholine in the aorta. The findings suggest that activation of the renin-angiotensin system contributes importantly to oxidative stress and endothelial dysfunction after endotoxin.

scholarly journals In Vitro and In Vivo Antioxidant Properties of Taraxacum officinale in Nω-Nitro-l-Arginine Methyl Ester (L-NAME)-Induced Hypertensive Rats

Antioxidants ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 309
Author(s):  
Olukayode O. Aremu ◽  
Adebola O. Oyedeji ◽  
Opeoluwa O. Oyedeji ◽  
Benedicta N. Nkeh-Chungag ◽  
Constance R. Sewani Rusike
Keyword(s):  
Oxidative Stress ◽  
Free Radical ◽  
Methyl Ester ◽  
Leaf Extract ◽  
Radical Scavenging ◽  
Free Radical Scavenging ◽  
Hypertensive Rats ◽  
Total Antioxidant

Oxidative stress has gained attention as one of the fundamental mechanisms responsible for the development of hypertension. The present study investigated in vitro and in vivo antioxidant effects of 70% ethanol-water (v/v) leaf and root extracts of T. officinale (TOL and TOR, respectively). Total phenolic and flavonoid content of plant extracts were assessed using Folin Ciocalteau and aluminium chloride colorimetric methods; while, 2,2-diphenyl-1-picrlhydrazyl (DPPH), 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and ferric reducing antioxidant power (FRAP) protocols were used to determine the free radical scavenging and total antioxidant capacities (TAC), respectively. The in vivo total antioxidant capacity and malondialdehyde acid (MDA) levels for lipid peroxidation tests were performed on organ homogenate samples from Nω-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats treated with leaf extract, TOL (500 mg/kg/day) and TOR (500 mg/kg/day) for 21 days. Results showed that compared to TOR, TOL possessed significantly higher (p < 0.01) polyphenol (4.35 ± 0.15 compared to 1.14 ± 0.01) and flavonoid (23.17 ± 0.14 compared to 3 ± 0.05) content; free radical scavenging activity (EC50 0.37 compared to 1.34 mg/mL) and total antioxidant capacities (82.56% compared to 61.54% ABTS, and 156 ± 5.28 compared to 40 ± 0.31 FRAP) and both extracts showed no toxicity (LD50 > 5000 mg/kg). TOL and TOR significantly (p < 0.01) elevated TAC and reduced MDA levels in targets organs. In conclusion, T. officinale leaf extract possesses significant anti-oxidant effects which conferred significant in vivo antioxidant protection against free radical-mediated oxidative stress in L-NAME-induced hypertensive rats.

scholarly journals Accelerated Repurposing and Drug Development of Pulmonary Hypertension Therapies for COVID-19 Treatment Using an AI-Integrated Biosimulation Platform

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1912
Author(s):  
Kaushik Chakravarty ◽  
Victor G. Antontsev ◽  
Maksim Khotimchenko ◽  
Nilesh Gupta ◽  
Aditya Jagarapu ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Renin Angiotensin System ◽  
Mechanistic Modeling ◽  
Channel Blockers ◽  
Angiotensin System ◽  
In Silico Modeling ◽  
Site Of Action ◽  
Line Of Therapy

The COVID-19 pandemic has reached over 100 million worldwide. Due to the multi-targeted nature of the virus, it is clear that drugs providing anti-COVID-19 effects need to be developed at an accelerated rate, and a combinatorial approach may stand to be more successful than a single drug therapy. Among several targets and pathways that are under investigation, the renin-angiotensin system (RAS) and specifically angiotensin-converting enzyme (ACE), and Ca2+-mediated SARS-CoV-2 cellular entry and replication are noteworthy. A combination of ACE inhibitors and calcium channel blockers (CCBs), a critical line of therapy for pulmonary hypertension, has shown therapeutic relevance in COVID-19 when investigated independently. To that end, we conducted in silico modeling using BIOiSIM, an AI-integrated mechanistic modeling platform by utilizing known preclinical in vitro and in vivo datasets to accurately simulate systemic therapy disposition and site-of-action penetration of the CCBs and ACEi compounds to tissues implicated in COVID-19 pathogenesis.

Androgens augment proximal tubule transport

2004 ◽  
Vol 287 (3) ◽  
pp. F452-F459 ◽  
Author(s):  
Albert Quan ◽  
Sumana Chakravarty ◽  
Jian-Kang Chen ◽  
Jian-Chun Chen ◽  
Samer Loleh ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Specific Binding ◽  
Extracellular Volume ◽  
Renin Angiotensin System ◽  
Angiotensin Receptors ◽  
Sprague Dawley ◽  
Angiotensin System ◽  
Renin Angiotensin

The proximal tubule contains an autonomous renin-angiotensin system that regulates transport independently of circulating angiotensin II. Androgens are known to increase expression of angiotensinogen, but the effect of androgens on proximal tubule transport is unknown. In this in vivo microperfusion study, we examined the effect of androgens on proximal tubule transport. The volume reabsorptive rate in Sprague-Dawley rats given dihydrotestosterone (DHT) injections was significantly higher than in control rats given vehicle injections (4.57 ± 0.31 vs. 3.31 ± 0.23 nl·min−1·mm−1, P < 0.01). Luminally perfusing with either enalaprilat (10−4 M) to inhibit production of angiotensin II or losartan (10−8 M) to block the angiotensin receptor decreased the proximal tubule volume reabsorptive rate in DHT-treated rats to a significantly greater degree than in control vehicle-injected rats. The renal expression of angiotensinogen was shown to be higher in the DHT-treated animals, using Northern blot analysis. The expression of angiotensin receptors, determined by specific binding of angiotensin II, was not different in the two groups of animals. Brush-border membrane protein abundance of the Na/H exchanger, a membrane transport protein under angiotensin II regulation, was also higher in DHT-treated rats vs. control rats. Rats that received DHT had higher blood pressures than the control rats but had no change in their glomerular filtration rate. In addition, serum angiotensin II levels were lower in DHT-treated vs. control rats. These results suggest that androgens may directly upregulate the proximal tubule renin-angiotensin system, increase the volume reabsorptive rate, and thereby increase extracellular volume and blood pressure and secondarily decrease serum angiotensin II levels.

Effects of Tokishakuyakusan, Keishibukuryogan, Shakuyakukanzoto and Unkeito on Ovarian Endothelin, Renin and Angiotensin II in Pregnant Mare's Serum Gonadotropin-treated Immature Rats

1992 ◽  
Vol 20 (02) ◽  
pp. 175-179 ◽  
Author(s):  
Satoshi Usuki ◽  
Yoshie Usuki ◽  
Junko Tanaka ◽  
Yuko Kawakura
Keyword(s):  
Angiotensin Ii ◽  
Herbal Medicines ◽  
Renin Angiotensin System ◽  
Concomitant Treatment ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Immature Rats ◽  
Serum Gonadotropin ◽  
Peptide System

We have previously proposed the ovarian ERAANPS (endothelin-renin-angiotensin-atrial natriuretic peptide system). The present study was undertaken to examine in vivo the effects of herbal medicines [Tokishakuyakusan (TS), Keishibukuryogan (KB), Shakuyakukanzoto (SK) and Unkeito (UT)] on endothelin-l (ET), renin and angiotensin II (A II) in the ovaries, of immature rats treated with 10 IU PMS for 48 h. ET and all components of renin-angiotensin system (RAS) were found at high levels in the ovary. Concomitant treatment with PMS plus TS, KB, SK or UT, especially TS and UT, tended to decrease the ET levels in ovary, while components of RAS tended to increase. However, ET, renin and A II levels in plasma were not at all affected after treatment with TS, KB, SK or UT. These results suggest that TS, KB, SK or UT may regulate the ovarian ERAANPS.

scholarly journals A novel mitochondrial enriched antioxidant protects neurons against acute oxidative stress

2017 ◽  
Author(s):  
Nicola J. Drummond ◽  
Nick O. Davies ◽  
Janet E. Lovett ◽  
Mark R. Miller ◽  
Graeme Cook ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Damage ◽  
Radical Scavenging ◽  
Head Group ◽  
Neural Cells ◽  
Zebrafish Model ◽  
Free System ◽  
Age Related

AbstractExcessive reactive oxygen species (ROS) can damage proteins, lipids, and DNA, which result in cell damage and death. The outcomes can be acute, as seen in stroke, or more chronic as observed in age-related diseases such as Parkinson’s disease. Here we investigate the antioxidant ability of a novel synthetic flavonoid, Proxison (7-decyl-3-hydroxy-2-(3,4,5-trihydroxyphenyl)-4-chromenone), using a range of in vitro and in vivo approaches. We show that, while it has radical scavenging ability on par with other flavonoids in a cell-free system, Proxison is orders of magnitude more potent than natural flavonoids at protecting neural cells against oxidative stress and is capable of rescuing damaged cells. The unique combination of a lipophilic hydrocarbon tail with a modified polyphenolic head group promotes efficient cellular uptake and mitochondrial localisation of Proxison. Importantly, in vivo administration of Proxison demonstrated effective and well tolerated neuroprotection against oxidative stress in a zebrafish model of dopaminergic neuronal loss.

IN-SILICO AND IN VITRO ASSESSMENT OF SYNTHESIZED DIAZENYLSULFONAMIDES AS APOPTOSIS INDUCERS AND RADICAL SCAVENGERS

INDIAN DRUGS ◽  
2020 ◽  
Vol 57 (06) ◽  
pp. 49-59
Author(s):  
Priyambada Kshiroda Nandini Sarangi ◽  
Jyotirmaya Sahoo ◽  
Chita Ranjan Sahoo ◽  
Sudhir Kumar Paidesetty ◽  
Guru Prasad Mohanta
Keyword(s):  
Cell Line ◽  
Cancer Cell ◽  
Radical Scavenging ◽  
Cancer Cell Line ◽  
Scavenging Effect ◽  
Ic50 Values ◽  
Radical Scavenging Effect ◽  
The Individual ◽  
Mcf 7

A series of eight quinoline-thiazole hybrid-bearing diazenylsulfonamides, 4a-4h, were synthesized and characterized by UV-Vis, FT/IR, 1H NMR and lC-MS. These compounds were formed when two prepared intermediate precursors of Schiff-base compounds, (E)-N-((2-chloroquinolin-3-yl)methylene)-4phenylthiazol-2-amine (3a) and (E)-N-((2-chloroquinolin-3-yl)methylene)-4-chlorophenylthiazol-2-amine (3b) were converted to the corresponding diazenyl compounds 4a-4h by treating and coupling with the individual diazonium salts of sulfa-drugs. The results of in vitro cytotoxic activity of the synthesized compounds in two cancer cell lines MCF 7 (human breast cancer cell line) and K562 (myelogenousleukemia cell line) have shown the IC50 values as given: 4b against MCF 7 19.52 and against K562 20.55µM; 4d against MCF 7 15.96 and against K562 13.05µM. Moreover, the compound 4-(((Z)-(2-chloroquinolin-3yl)(4-phenylthiazol-2-ylimino)methyl)diazenyl)benzenesulfonic acid (4d) induced maximum percentage of apoptosis. Furthermore, the in vitro antioxidant activity study revealed that among all the synthesized compounds, compound 4d has an excellent radical scavenging effect. Molecular docking was additionally performed to investigate the binding affinity of H-bonding interaction of synthesized compounds with a targeted enzyme and to compare it with the anticancer drugs, dasatinib, bosutinib and dacarbazine.

The Role of the Renin–Angiotensin System in the Cancer Stem Cell Niche

2021 ◽  
pp. 002215542110262
Author(s):  
Ethan J. Kilmister ◽  
Swee T. Tan
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Signaling Pathways ◽  
Renin Angiotensin System ◽  
Epidemiological Data ◽  
Malignant Cells ◽  
Angiotensin System ◽  
Renin Angiotensin

Cancer stem cells (CSCs) drive metastasis, treatment resistance, and tumor recurrence. CSCs reside within a niche, an anatomically distinct site within the tumor microenvironment (TME) that consists of malignant and non-malignant cells, including immune cells. The renin–angiotensin system (RAS), a critical regulator of stem cells and key developmental processes, plays a vital role in the TME. Non-malignant cells within the CSC niche and stem cell signaling pathways such as the Wnt, Hedgehog, and Notch pathways influence CSCs. Components of the RAS and cathepsins B and D that constitute bypass loops of the RAS are expressed on CSCs in many cancer types. There is extensive in vitro and in vivo evidence showing that RAS inhibition reduces tumor growth, cell proliferation, invasion, and metastasis. However, there is inconsistent epidemiological data on the effect of RAS inhibitors on cancer incidence and survival outcomes, attributed to different patient characteristics and methodologies used between studies. Further mechanistic studies are warranted to investigate the precise effects of the RAS on CSCs directly and/or the CSC niche. Targeting the RAS, its bypass loops, and convergent signaling pathways participating in the TME and other key stem cell pathways that regulate CSCs may be a novel approach to cancer treatment:

scholarly journals In Vitro and In Vivo Antioxidant Activity of the New Magnetic-Cerium Oxide Nanoconjugates

Nanomaterials ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 1565 ◽  
Author(s):  
Turin-Moleavin ◽  
Fifere ◽  
Lungoci ◽  
Rosca ◽  
Coroaba ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activity ◽  
Iron Oxide ◽  
Cerium Oxide ◽  
Chemical Activation ◽  
Radical Scavenging ◽  
Cerium Oxide Nanoparticles ◽  
Oxide Nanoparticles

Background. Cerium oxide nanoparticles present the mimetic activity of superoxide dismutase, being able to inactivate the excess of reactive oxygen species (ROS) correlated with a large number of pathologies, such as stents restenosis and the occurrence of genetic mutations that can cause cancer. This study presents the synthesis and biological characterisation of nanoconjugates based on nanoparticles of iron oxide interconnected with cerium oxide conjugates. Methods. The synthesis of magnetite-nanoceria nanoconjugates has been done in several stages, where the key to the process is the coating of nanoparticles with polyethyleneimine and its chemical activation-reticulation with glutaraldehyde. The nanoconjugates are characterised by several techniques, and the antioxidant activity was evaluated in vitro and in vivo. Results. Iron oxide nanoparticles interconnected with cerium oxide nanoparticles were obtained, having an average diameter of 8 nm. Nanoconjugates prove to possess superparamagnetic properties and the saturation magnetisation varies with the addition of diamagnetic components in the system, remaining within the limits of biomedical applications. In vitro free-radical scavenging properties of nanoceria are improved after the coating of nanoparticles with polyethylenimine and conjugation with magnetite nanoparticles. In vivo studies reveal increased antioxidant activity in all organs and fluids collected from mice, which demonstrates the ability of the nanoconjugates to reduce oxidative stress. Conclusion. Nanoconjugates possess magnetic properties, being able to scavenge free radicals, reducing the oxidative stress. The combination of the two properties mentioned above makes them excellent candidates for theranostic applications.

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