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https://www.readbyqxmd.com/read/29768080/effects-of-quercetin-on-the-pharmacokinetics-of-losartan-and-its-metabolite-exp3174-in-rats
#1
Qingling Zhao, Jinlan Wei, Hongying Zhang
1. This study investigates the influence of quercetin on the pharmacokinetics of losartan and its metabolite EXP3174 in rats. 2. The pharmacokinetic profiles of losartan and EXP3174 of orally administered losartan (10 mg/kg) with or without pretreatment with quercetin (20 mg/kg/day for 7 days) were investigated. Additionally, Caco-2 cell transwell model and rat liver microsome incubation experiments were also conducted to investigate its potential mechanism. 3. The results showed that when the rats were pretreated with quercetin, the Cmax (2...
May 16, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29765495/effect-of-the-antioxidant-lipoic-acid-in-aortic-phenotype-in-a-marfan-syndrome-mouse-model
#2
Maria C Guido, Victor Debbas, Vera M Salemi, Elaine R Tavares, Thayna Meirelles, Thaís L S Araujo, Patricia Nolasco, Julio C A Ferreira-Filho, Celso K Takimura, Lygia V Pereira, Francisco R Laurindo
Marfan syndrome (MFS) cardiovascular manifestations such as aortic aneurysms and cardiomyopathy carry substantial morbidity/mortality. We investigated the effects of lipoic acid, an antioxidant, on ROS production and aortic remodeling in a MFS mgΔloxPneo mouse model. MFS and WT (wild-type) 1-month-old mice were allocated to 3 groups: untreated, treated with losartan, and treated with lipoic acid. At 6 months old, echocardiography, ROS production, and morphological analysis of aortas were performed. Aortic ROS generation in 6-month-old MFS animals was higher at advanced stages of disease in MFS...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29754503/hesperidin-suppresses-renin-angiotensin-system-mediated-nox2-over-expression-and-sympathoexcitation-in-2k-1c-hypertensive-rats
#3
Chutamas Wunpathe, Prapassorn Potue, Putcharawipa Maneesai, Sarawoot Bunbupha, Parichat Prachaney, Upa Kukongviriyapan, Veerapol Kukongviriyapan, Poungrat Pakdeechote
Hesperidin, a flavonoid derived from citrus fruits, possesses several beneficial effects including anti-oxidation and anti-inflammation. The aim of this study was to investigate the effects of hesperidin on the renin-angiotensin system (RAS) cascade that mediated oxidative stress and sympathoexcitation in two-kidney, one-clipped (2K-1C) hypertensive rats. 2K-1C hypertension was induced in male Sprague-Dawley rats. Hypertensive rats were treated with hesperidin at 20[Formula: see text]mg/kg or 40[Formula: see text]mg/kg or losartan at 10[Formula: see text]mg/kg beginning at three weeks after surgery and then continued for four weeks ([Formula: see text]/group)...
May 13, 2018: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29753374/beneficial-effects-of-pentoxifylline-plus-losartan-dual-therapy-in-type-2-diabetes-with-nephropathy
#4
Soghra Rabizadeh, Fatemeh Dehghani Firouzabadi, Sina Noshad, Sadaf Esteghamati, Mohsen Afarideh, Alireza Ghajar, Morsaleh Ganji, Mohammad Saadat, Behnam Heidari, Mohammad Taghi Najafi, Manouchehr Nakhjavani, Alireza Esteghamati
BACKGROUND: This study was designed to comparatively assess the effects of add-on pentoxifylline to losartan versus increasing the dose of losartan on serum N-terminal pro-brain natriuretic peptide (NT-proBNP), serum highly sensitive C-reactive protein (hsCRP) and the urinary albumin excretion (UAE) rate in patients with type 2 diabetes and nephropathy. METHODS: In an open-label, single-center, parallel-group, randomized clinical trial (NCT03006952), 30 patients received b...
May 2018: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/29753173/comparative-effects-of-avocado-oil-and-losartan-on-blood-pressure-renal-vascular-function-and-mitochondrial-oxidative-stress-in-hypertensive-rats
#5
Cristian Adrián Márquez-Ramírez, José Lucio Hernández de la Paz, Omar Ortiz-Avila, Andrés Raya-Farias, Juan Carlos González-Hernández, Alain Raimundo Rodríguez-Orozco, Rafael Salgado-Garciglia, Alfredo Saavedra-Molina, Daniel Godínez-Hernández, Christian Cortés-Rojo
OBJECTIVE: Angiotensin II (Ang-II) antagonism alleviates hypertensive kidney damage by improving mitochondrial function and decreasing oxidative stress. This condition also is associated with altered renal vascular tone due to enhanced constriction by Ang-II. Thus, approaches ameliorating these events are desirable to alleviate kidney damage. Avocado oil, a source of antioxidants and oleic acid, is known to improve mitochondrial function, while oleic acid has antihypertensive effects...
March 20, 2018: Nutrition
https://www.readbyqxmd.com/read/29750475/effects-of-losartan-and-allopurinol-on-cardiorespiratory-regulation-in-obstructive-sleep-apnoea
#6
Barbara J Morgan, Mihaela Teodorescu, David F Pegelow, Emily R Jackson, Devin L Schneider, David T Plante, James P Gapinski, Scott J Hetzel, John M Dopp
Chemoreflex sensitization produced by chronic intermittent hypoxia (CIH) in rats is attenuated by angiotensin II type 1 receptor (AT1 R) blockade. AT1 R blockade and xanthine oxidase inhibition both ameliorate CIH-induced endothelial dysfunction. We hypothesized treatment with losartan and allopurinol would reduce chemoreflex sensitivity and improve hypoxic vasodilation in patients with obstructive sleep apnoea (OSA). Eighty-six hypertensive patients with apnoea-hypopnoea index ≥25 events/hr and no other cardiovascular, pulmonary, renal, or metabolic disease were randomly assigned to receive allopurinol, losartan, or placebo for 6 weeks...
May 11, 2018: Experimental Physiology
https://www.readbyqxmd.com/read/29748863/repaglinide-irbesartan-drug-interaction-effects-of-slco1b1-polymorphism-on-repaglinide-pharmacokinetics-and-pharmacodynamics-in-chinese-population
#7
Qi Pei, Jun-Yan Liu, Ji-Ye Yin, Guo-Ping Yang, Shi-Kun Liu, Yi Zheng, Pan Xie, Cheng-Xian Guo, Mi Luo, Hong-Hao Zhou, Xi Li, Zhao-Qian Liu
PURPOSE: On account of the potential inhibition of OATP1B1 (organic anion transporting polypeptide) by angiotensin II receptor blockers (ARBs) and the effects of SLCO1B1 (solute carrier organic anion transporter family member) polymorphism, the aim of current study is to assess the impact of ARBs on the pharmacokinetics (PK) and pharmacodynamics (PD) of repaglinide in Chinese healthy volunteers with different SLCO1B1 genotypes. METHODS: The in vitro study was conducted on irbesartan, valsartan, olmesartan, and losartan by using HEK293 cells transfected with OATP1B1...
May 11, 2018: European Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/29748710/critical-role-of-angiotensin-ii-type-2-receptors-in-the-control-of-mitochondrial-and-cardiac-function-in-angiotensin-ii-preconditioned-rat-hearts
#8
Rebeca E Nuñez, Sabzali Javadov, Nelson Escobales
Angiotensin II preconditioning (APC) involves an angiotensin II type 1 receptor (AT1-R)-dependent translocation of PKCε and survival kinases to the mitochondria leading to cardioprotection after ischemia-reperfusion (IR). However, the role that mitochondrial AT1-Rs and angiotensin II type 2 receptors (AT2-Rs) play in APC is unknown. We investigated whether pretreatment of Langendorff-perfused rat hearts with losartan (L, AT1-R blocker), PD 123,319 (PD, AT2-R blocker), or their combination (L + PD) affects mitochondrial AT1-R, AT2-R, PKCε, PKCδ, Akt, PKG-1, MAPKs (ERK1/2, JNK, p38), mitochondrial respiration, cardiac function, and infarct size (IS)...
May 10, 2018: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29746595/insights-into-molecular-mechanisms-of-drug-metabolism-dysfunction-of-human-cyp2c9-30
#9
Maxime Louet, Céline M Labbé, Charline Fagnen, Cassiano M Aono, Paula Homem-de-Mello, Bruno O Villoutreix, Maria A Miteva
Cytochrome P450 2C9 (CYP2C9) metabolizes about 15% of clinically administrated drugs. The allelic variant CYP2C9*30 (A477T) is associated to diminished response to the antihypertensive effects of the prodrug losartan and affected metabolism of other drugs. Here, we investigated molecular mechanisms involved in the functional consequences of this amino-acid substitution. Molecular dynamics (MD) simulations performed for the active species of the enzyme (heme in the Compound I state), in the apo or substrate-bound state, and binding energy analyses gave insights into altered protein structure and dynamics involved in the defective drug metabolism of human CYP2C9...
2018: PloS One
https://www.readbyqxmd.com/read/29746172/pharmacological-decrease-of-liver-stiffness-is-pressure-related-and-predicts-long-term-clinical-outcome
#10
Felix Piecha, Mattias Mandorfer, Teresa Peccerella, Ann-Kathrin Ozga, Tanja Poth, Anna Vonbank, Helmut Karl Seitz, Vanessa Rausch, Thomas Reiberger, Sebastian Mueller
Liver stiffness (LS) as measured by transient elastography is increasingly used to non-invasively assess liver fibrosis. However, LS is efficiently modulated by confounders like arterial and portal pressure (PP). We here study the effect of acute hemodynamic changes on LS (measured by µFibroscan) in a rodent model of cirrhosis in response to pharmacological modulation of PP by losartan, NO-donors and propranolol. Additionally, changes of LS and the hepatic venous pressure gradient (HVPG) under propranolol therapy were assessed with regard to clinical outcomes in a human cohort of n=38 cirrhotic patients...
May 10, 2018: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/29744294/synergistic-effects-of-hmg-coa-reductase-inhibitor-and-angiotensin-ii-receptor-blocker-on-load-induced-heart-failure
#11
Yusuke Ito, Yasuhiro Maejima, Natsuko Tamura, Yuka Shiheido-Watanabe, Masanori Konishi, Takashi Ashikaga, Kenzo Hirao, Mitsuaki Isobe
5-Hydroxy-3-methylglutaryl-CoA reductase inhibitors (statins) have beneficial effects in patients with heart failure (HF), regardless of serum cholesterol levels. However, their synergic effects with angiotensin II receptor blocker (ARB) remain to be established. We assessed the existence and potential underlying mechanisms of the effects of combined ARB [losartan (LOS)] and statin [simvastatin (SIM)] on cardiac function in rats and mice with load-induced HF. Salt-loaded Dahl salt-sensitive (DS) rats were treated with vehicle, LOS, SIM, or LOS + SIM for 8 weeks...
May 2018: FEBS Open Bio
https://www.readbyqxmd.com/read/29731445/synthesis-characterization-and-antihypertensive-activity-of-2-phenyl-substituted-benzimidazoles
#12
Muhammad Tariq Khan, Muhammad Tahir Razi, Syed Umer Jan, Muhammad Mukhtiar, Rahman Gul, - IzharUllah, Abid Hussain, Asif Mehmood Hashmi, Muhammad Taufiq Ahmad, Nisar Ahmed Shahwani, Imran Rabbani
Hypertension is one of cardiovascular disease that is not sufficiently prevented and controlled at both hospital and community levels. Hypertension resulted in significant morbidity and mortality. The benz-imidazole ring is very important pharmacophore in modern drug discovery. The substituted benzimidazoles are the important for medicinal research. Researchers have reported that substituted Benzimidazoles are the structural isosteres of nucleotides, and easily allow them to interact with the different biopolymers, possess pharmacological activity especially antihypertensive activity...
May 2018: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29729681/up-regulation-of-renal-renin-angiotensin-system-and-inflammatory-mechanisms-in-the-prenatal-programming-by-low-protein-diet-beneficial-effect-of-the-post-weaning-losartan-treatment
#13
I K M Watanabe, Z P Jara, R A Volpini, M D C Franco, F F Jung, D E Casarini
Previous studies have shown that the renin-angiotensin system (RAS) is affected by adverse maternal nutrition during pregnancy. The aim of this study was to investigate the effects of a maternal low-protein diet on proinflammatory cytokines, reactive oxygen species and RAS components in kidney samples isolated from adult male offspring. We hypothesized that post-weaning losartan treatment would have beneficial effects on RAS activity and inflammatory and oxidative stress markers in these animals. Pregnant Sprague-Dawley rats were fed with a control (20% casein) or low-protein diet (LP) (6% casein) throughout gestation...
May 6, 2018: Journal of Developmental Origins of Health and Disease
https://www.readbyqxmd.com/read/29727629/losartan-prevents-the-imbalance-between-renal-dopaminergic-and-renin-angiotensin-systems-induced-by-fructose-overload-l-dopa-dopamine-index-as-new-potential-biomarker-of-renal-dysfunction
#14
Natalia Lucía Rukavina Mikusic, Nicolás Martín Kouyoumdzian, Ana Uceda, Julieta Sofía Del Mauro, Marcela Pandolfo, Mariela Mercedes Gironacci, Ana María Puyó, Jorge Eduardo Toblli, Belisario Enrique Fernández, Marcelo Roberto Choi
BACKGROUND: The renin angiotensin system (RAS) and the renal dopaminergic system (RDS) act as autocrine and paracrine systems to regulate renal sodium management and inflammation and their alterations have been associated to hypertension and renal damage. Nearly 30-50% of hypertensive patients have insulin resistance (IR), with a strong correlation between hyperinsulinemia and microalbuminuria. OBJECTIVE: The aim of this study was to demonstrate the existence of an imbalance between RAS and RDS associated to IR, hypertension and kidney damage induced by fructose overload (FO), as well as to establish their prevention, by pharmacological inhibition of RAS with losartan...
May 1, 2018: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29723078/-evaluation-of-the-losartan-solubility-in-the-biowaiver-context-by-shake-flask-method-and-intrinsic-dissolution
#15
Janine Braga de Souza, Jacqueline de Souza, Lara Maria Lopes de Castro, Melissa Fabíola Siqueira, Ranylson Marcello Leal Savedra, Neila Márcia Silva-Barcellos
This study aimed at evaluating the shake-flask use as a universal method to evaluate drug solubility in a biowaiver context as proposed by FDA, EMA and ANVISA. The solubility of losartan was determined in three buffers using the shake-flask method, intrinsic dissolution (ID) and Quantum Chemistry. Moreover, the evaluation of a losartan dissolution profile from coated tablets was conducted. The losartan low solubility in pH 1.2 and high solubility in pH 6.8 was observed using the shake-flask method. However, the solubility results using ID demonstrated its high solubility in pH1...
May 3, 2018: Pharmaceutical Development and Technology
https://www.readbyqxmd.com/read/29709898/angiotensin-ii-aggravates-lipopolysaccharide-induced-human-pulmonary-microvascular-endothelial-cells-permeability-in-high-glucose-status
#16
Min Chen, Chang Chen, Xiaohui Yuan, Xiaoqi Chen, Feng Zheng, Liang Shao, Zongze Zhang
Lung infection is one of the most common infections in diabetes mellitus and is characterized by increased pulmonary microvascular endothelial permeability. Local Angiotensin II (AngII) plays an important role in the pathogenesis of lung diseases. However, whether AngII can aggravate diabetic infectious lung injury is not clear. Therefore, we investigated the effects of AngII on the permeability of human pulmonary microvascular endothelial cells (HPMVECs) challenged by lipopolysaccharide (LPS) in high glucose states in vitro...
April 28, 2018: Endocrine Journal
https://www.readbyqxmd.com/read/29704812/%C3%B0-theoretical-study-on-ionization-of-sartans-in-aqueous-media-and-on-interactions-with-surfactant-micelles
#17
Marija R Popović-Nikolić, Gordana V Popović, Maja Grujić, Katarina M Nikolić, Danica D Agbaba
The ionization order of sartans in aqueous media and possible way of interactions between their equilibrium forms and surfactant micelles have been theoretically investigated. The examined sartans are ampholytes (irbesartan and losartan) and a diacid (valsartan) with the close values of ionization constants. In order to get a better insight in the overlapped protolytic equilibria of sartans and to predict an affinity of the equilibrium forms interacting with micelles as biomembrane mimetic systems, the theoretical study was performed...
April 20, 2018: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/29702076/prevention-of-progression-of-diabetic-nephropathy-by-the-sglt2-inhibitor-ipragliflozin-in-uninephrectomized-type-2-diabetic-mice
#18
Atsuo Tahara, Toshiyuki Takasu
Diabetic nephropathy is the leading cause of end-stage renal disease in the world. Although recent development of sodium-glucose cotransporter (SGLT) 2 inhibitors offers a new antidiabetic therapeutic strategy, it remains unclear whether such treatments are beneficial for limiting the progression of type 2 diabetic overt nephropathy. This study examined the effect of the SGLT2 inhibitor ipragliflozin on the progression of nephropathy in uninephrectomized KK/Ay type 2 diabetic mice, which exhibit not only typical diabetic symptoms such as hyperglycemia, hyperinsuemia, glucose intolerance, insulin resistance, hyperlipidemia, inflammation, and obesity, but also moderate hypertension and overt nephropathy with decline in renal function...
April 24, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29689561/urate-lowering-agents-in-asymptomatic-hyperuricemia-role-of-urine-sediment-analysis-and-musculoskeletal-ultrasound
#19
Davide Viggiano, Giuseppe Gigliotti, Gianfranco Vallone, Anna Giammarino, Michelangelo Nigro, Giovambattista Capasso
Current urate-lowering therapy (ULT) includes three direct acting drugs (allopurinol, febuxostat, Rasburicase) and at least four 'indirect' drugs with other important targets (canagliflozin, losartan, fenofibrate and sevelamer). Moreover, the alcalinization of urines using bicarbonate can be used to dissolve urate crystals and the clinician may discontinue several drugs are known to increase serum levels of uric acid, such as diuretics, aspirin, cyclosporine, theophylline, mycophenolate and ACE inhibitors. While there is a consensus to start ULT in cases of symptomatic hyperuricemia (gout, urate-nephrolithiasis), the very frequent conditions of asymptomatic hyperuricemia remains a major conundrum...
April 19, 2018: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29685075/synergistic-effect-of-cranberry-extract-and-losartan-against-aluminium-chloride-induced-hepatorenal-damage-associated-cardiomyopathy-in-rats
#20
Shereen Mohamed Galal, Hesham Farouk Hasan, Mohamed Khairy Abdel-Rafei, Shereen Mohamed El Kiki
The present study was designed to evaluate the effect of cranberry extract (CRAN) and/or losartan (LOS) against aluminium chloride (AlCl3 ) induced hepatorenal damage associated cardiomyopathy in rats. To induce hepatorenal and cardiotoxicity, animals were received (AlCl3 ; 70 mg/kg i.p.) for 8 weeks day after day and treated with CRAN (100 mg/kg b.wt.) orally daily for 4 weeks started after 4 weeks from AlCl3 injection accompanied with an administration of LOS (5 mg/kg i.p.) three times weekly for 4 weeks...
April 23, 2018: Archives of Physiology and Biochemistry
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