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Hepatic angiotensin

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https://www.readbyqxmd.com/read/28421320/hepatocyte-specific-depletion-of-ubiquitin-regulatory-x-domain-containing-protein-8-accelerates-fibrosis-in-a-mouse-non-alcoholic-steatohepatitis-model
#1
Norihiro Imai, Michitaka Suzuki, Yoji Ishizu, Teiji Kuzuya, Takashi Honda, Kazuhiko Hayashi, Masatoshi Ishigami, Yoshiki Hirooka, Tetsuya Ishikawa, Hidemi Goto, Toyoshi Fujimoto
Ubiquitin regulatory X domain-containing protein 8 (UBXD8) is engaged in the degradation of lipidated apolipoprotein B in hepatocytes. We previously showed that hepatocyte-specific UBXD8-deficient mice (U8-HKO) fed a moderately high-fat diet (31 kcal % fat) showed periportal macrovesicular steatosis along with a decrease in very low-density lipoprotein secretion, but did not develop fibrosis. In the present study, we examined whether U8-HKO mice show NASH-like phenotypes when fed a very high-fat diet (60 kcal % fat)...
April 18, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28417439/clinical-pharmacokinetics-of-sacubitril-valsartan-lcz696-a-novel-angiotensin-receptor-neprilysin-inhibitor
#2
REVIEW
Surya Ayalasomayajula, Thomas Langenickel, Parasar Pal, Sreedevi Boggarapu, Gangadhar Sunkara
Sacubitril/valsartan (LCZ696) is indicated for the treatment of heart failure with reduced ejection fraction. Absorption of sacubitril/valsartan and conversion of sacubitril (prodrug) to sacubitrilat (neprilysin inhibitor) was rapid with maximum plasma concentrations of sacubitril, sacubitrilat, and valsartan (angiotensin receptor blocker) reaching within 0.5, 1.5-2.0, and 2.0-3.0 h, respectively. With a two-fold increase in dose, an increase in the area under the plasma concentration-time curve was proportional for sacubitril, ~1...
April 17, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28414295/high-salt-intake-reprioritizes-osmolyte-and-energy-metabolism-for-body-fluid-conservation
#3
Kento Kitada, Steffen Daub, Yahua Zhang, Janet D Klein, Daisuke Nakano, Tetyana Pedchenko, Louise Lantier, Lauren M LaRocque, Adriana Marton, Patrick Neubert, Agnes Schröder, Natalia Rakova, Jonathan Jantsch, Anna E Dikalova, Sergey I Dikalov, David G Harrison, Dominik N Müller, Akira Nishiyama, Manfred Rauh, Raymond C Harris, Friedrich C Luft, David H Wassermann, Jeff M Sands, Jens Titze
Natriuretic regulation of extracellular fluid volume homeostasis includes suppression of the renin-angiotensin-aldosterone system, pressure natriuresis, and reduced renal nerve activity, actions that concomitantly increase urinary Na+ excretion and lead to increased urine volume. The resulting natriuresis-driven diuretic water loss is assumed to control the extracellular volume. Here, we have demonstrated that urine concentration, and therefore regulation of water conservation, is an important control system for urine formation and extracellular volume homeostasis in mice and humans across various levels of salt intake...
April 17, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28356040/the-relevance-of-dietary-polyphenols-in-cardiovascular-protection
#4
Ana Gabriela Murillo, Maria Luz Fernandez
The chemical structure of polyphenols consisting of aromatic rings, capable of quenching free radicals, makes them ideal candidates to protect against oxidation. Polyphenols are present in a variety of foods including grapes, berries, dark chocolate, coffee and tea to mention a few. A number of studies have shown that dietary polyphenols exert a protective effect against hypertension, dyslipidemias, inflammation, endothelial function and atherosclerosis, conditions associated with increased risk for cardiovascular disease...
March 29, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28330766/water-metabolism-dysfunction-via-renin-angiotensin-system-activation-caused-by-liver-damage-in-mice-treated-with-microcystin-rr
#5
Qing Zhong, Feng Sun, Weiguang Wang, Wenqing Xiao, Xiaoni Zhao, Kangding Gu
Microcystins (MCs) are a group of monocyclic heptapeptide toxins that have been shown to act as potent hepatotoxins. However, the observed symptoms of water metabolism disruption induced by microcystin-RR (MC-RR) or MCs have rarely been reported, and a relatively clear mechanism has not been identified. In the present study, male mice were divided into 4 groups (A: 140μg/kg, B: 70μg/kg,C: 35μg/kg, and D: 0μg/kg) and administered MC-RR daily for a month. On day 8 of treatment, an increase in water intake and urine output was observed in the high-dose group compared with the control, and the symptoms worsened with the repeated administration of the toxin until day 30...
March 19, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28290069/significance-of-genetic-polymorphisms-in-patients-with-nonalcoholic-fatty-liver-disease
#6
REVIEW
Hisamitsu Miyaaki, Kazuhiko Nakao
Because of recent advances in genetic research such as genome-wide association studies, the underlying genetic mechanisms of nonalcoholic fatty liver disease (NAFLD) pathophysiology have been elucidated. Here, we present a review of the current literature on the impact of genetic polymorphisms in patients with NAFLD. These genetic polymorphisms, which regulate lipid metabolism, glucose metabolism, and the renin-angiotensin system, are involved in NAFLD onset, steatosis, inflammation, fibrosis, and hepatocellular carcinoma (HCC)...
March 13, 2017: Clinical Journal of Gastroenterology
https://www.readbyqxmd.com/read/28285069/sacubitril-valsartan-the-newest-addition-to-the-toolbox-for-guideline-directed-medical-therapy-of-heart-failure
#7
REVIEW
Jo E Rodgers
Sacubitril/valsartan combines a neprilysin inhibitor with an angiotensin receptor blocker. As an inhibitor of neprilysin, an enzyme that degrades biologically active natriuretic peptides, this first-in-class therapy increases levels of circulating natriuretic peptides, resulting in natriuretic, diuretic, and vasodilatory effects. In patients with chronic New York Heart Association class II-IV heart failure with reduced ejection fraction, the PARADIGM-HF trial demonstrated that sacubitril/valsartan significantly reduced the primary endpoint of cardiovascular mortality and heart failure hospitalization, compared with enalapril...
March 9, 2017: American Journal of Medicine
https://www.readbyqxmd.com/read/28283858/combination-therapy-with-lamivudine-and-angiotensin-converting-enzyme-inhibitor-angiotensin-receptor-blocker-for-hepatitis-b-virus-associated-glomerulonephritis-with-mild-to-moderate-proteinuria-a-clinical-review-of-38-cases
#8
Li-Jing Sun, Jian-Ping Shan, Ruo-Lan Cui, Wei-Jie Yuan, Geng-Ru Jiang
PURPOSE: The treatment of HBV-associated glomerulonephritis (HBV-GN) is still a challenge in clinical practice now. The objective of this study was to report the pathological characteristics of HBV-GN presenting with mild to moderate proteinuria and to evaluate the therapeutic efficacy of lamivudine (LAM) in combination with angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) as compared to ACEI/ARB monotherapy. METHODS: We conducted a retrospective observational study in HBV-GN patients between 2005 and 2014...
March 10, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28263289/establishment-of-a-mouse-model-of-enalapril-induced-liver-injury-and-investigation-of-the-pathogenesis
#9
Yuji Shirai, Shingo Oda, Sayaka Makino, Koichi Tsuneyama, Tsuyoshi Yokoi
Drug-induced liver injury (DILI) is a major concern in drug development and clinical drug therapy. Since the underlying mechanisms of DILI have not been fully understood in most cases, elucidation of the hepatotoxic mechanisms of drugs is expected. Although enalapril (ELP), an angiotensin-converting enzyme inhibitor, has been reported to cause liver injuries with a low incidence in humans, the precise mechanisms by which ELP causes liver injury remains unknown. In this study, we established a mouse model of ELP-induced liver injury and analyzed the mechanisms of its hepatotoxicity...
March 6, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28207324/is-serum-angiotensin-converting-enzyme-level-useful-for-determining-necroinflammatory-activity-in-chronic-hepatitis-b-infection
#10
Ahmet Tay, Fatih Albayrak, Sevilay Ozmen, Ayse Albayrak, Kemalettin Ozden
AIM: The purpose of this study was to investigate the relationship between the findings from liver biopsy and the serum angiotensin-converting enzyme (ACE) level to determine whether ACE might serve as a potential noninvasive sign of necroinflammatory activity in patients with Chronic Hepatitis B (CHB) infection. METHODS: A total of 54 CHB patients referred for liver biopsy were enrolled in the study. Serum ACE levels were determined photometrically with a kinetic test...
February 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28164519/angiotensin-converting-enzyme-inhibitors-influence-on-antiplatelet-therapy-of-clopidogrel-in-acs
#11
Shuo Yang, Chanjuan Cui, Jie Zhang, Rui Qiao
BACKGROUND: Clopidogrel is a prodrug, the minority of which is converted to an active metabolite by hepatic cytochrome P450 (CYP2C19), however, most of it is metabolized to inactive substance by hepatic carboxylesterase1 (CES1). Meanwhile angiotensin-converting enzyme inhibitors (ACEIs) are mostly metabolized by CES1. We aimed to assess the impact of ACEIs on platelet inhibition by clopidogrel. METHODS: We genotyped variants CES1, CYP2C19*2 and *3 in 502 patients with acute coronary syndrome (ACS) receiving clopidogrel therapy, and analyzed the effects of ACEIs on responsiveness to clopidogrel by the vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay and ADP-stimulated impedance whole blood platelet aggregation assay...
October 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28144388/hepatic-structural-enhancement-and-insulin-resistance-amelioration-due-to-at1-receptor-blockade
#12
EDITORIAL
Vanessa Souza-Mello
Over the last decade, the role of renin-angiotensin system (RAS) on the development of obesity and its comorbidities has been extensively addressed. Both circulating and local RAS components are up-regulated in obesity and involved in non-alcoholic fatty liver disease onset. Pharmacological manipulations of RAS are viable strategies to tackle metabolic impairments caused by the excessive body fat mass. Renin inhibitors rescue insulin resistance, but do not have marked effects on hepatic steatosis. However, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ARB) yield beneficial hepatic remodeling...
January 18, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28029729/combined-treatment-with-dipeptidyl-peptidase-4-inhibitor-sitagliptin-and-angiotensin-ii-type-1-receptor-blocker-losartan-suppresses-progression-in-a-non-diabetic-rat-model-of-steatohepatitis
#13
Yasushi Okura, Tadashi Namisaki, Kei Moriya, Mitsuteru Kitade, Kosuke Takeda, Kosuke Kaji, Ryuichi Noguchi, Norihisa Nishimura, Kenichiro Seki, Hideto Kawaratani, Hiroaki Takaya, Shinya Sato, Yasuhiko Sawada, Naotaka Shimozato, Masanori Furukawa, Keisuke Nakanishi, Soichiro Saikawa, Takuya Kubo, Kiyoshi Asada, Hitoshi Yoshiji
AIM: Dipeptidyl peptidase-4 (DPP4) inhibitors (DPP4-I) are oral glucose-lowering drugs for type 2 diabetes mellitus. Previously, we reported that DPP4-I (sitagliptin) exerted suppressive effects on experimental liver fibrosis in rats. Blockade of the renin-angiotensin system by angiotensin-II type 1 receptor blocker (losartan), commonly used in the management of hypertension, has been shown to significantly alleviate hepatic fibrogenesis and carcinogenesis. We aimed to elucidate the effects and possible mechanisms of a sitagliptin + losartan combination on the progression of non-diabetic non-alcoholic steatohepatitis (NASH) in a rat model...
December 28, 2016: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/27976638/effect-of-angiotensin-converting-enzyme-inhibitor-lisinopril-on-morphological-and-biochemical-aspects-of-fibrotic-liver-regeneration
#14
Aysha Ambreen, Sarwat Jahan, Satwat Malik
BACKGROUND/AIMS: Hepatic fibrosis results in defective liver regeneration following partial hepatectomy. Angiotensin converting enzyme (ACE) inhibitors can enhance liver regeneration and are also involved in the reduction of hepatic fibrosis. The present study has been conducted to evaluate the potential effect of an ACE inhibitor, lisinopril, on the morphological and biochemical aspects of fibrotic liver regeneration. MATERIALS AND METHODS: Eight-week old female Sprague Dawley rats were made fibrotic by intragastric carbon tetrachloride treatment...
November 2016: Saudi Journal of Gastroenterology: Official Journal of the Saudi Gastroenterology Association
https://www.readbyqxmd.com/read/27919004/irbesartan-ameliorates-hyperlipidemia-and-liver-steatosis-in-type-2-diabetic-db-db-mice-via-stimulating-ppar-%C3%AE-ampk-akt-mtor-signaling-and-autophagy
#15
Juan Zhong, Wangqiu Gong, Lu Lu, Jing Chen, Zibin Lu, HongYu Li, Wenting Liu, Yangyang Liu, Mingqing Wang, Rong Hu, Haibo Long, Lianbo Wei
Irbesartan (Irb), a unique subset of angiotensin II receptor blockers (ARBs) with PPAR-γ activation function, has been reported to play a role in renal dysfunction, glucose metabolism, and abnormal lipid profile in diabetic animal models and humans. However, the underlying mechanisms that improve hyperlipidemia and liver steatosis are unclear. This study investigated the effects of Irb on lipid metabolism and hepatic steatosis using the spontaneous type 2 diabetic db/db mouse model. The results demonstrated body and liver weight, food consumption, lipid content in serum and liver tissue, and liver dysfunction as well as hepatic steatosis were increased in db/db mice compared with db/m mice, whereas the increases were reversed by Irb treatment...
January 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/27917265/novel-non-invasive-biological-predictive-index-for-liver-fibrosis-in-hepatitis-c-virus-genotype-4-patients
#16
Mahmoud Khattab, Mohamed Amin Sakr, Mohamed Abdel Fattah, Youssef Mousa, Elwy Soliman, Ashraf Breedy, Mona Fathi, Salwa Gaber, Ahmed Altaweil, Ashraf Osman, Ahmed Hassouna, Ibrahim Motawea
AIM: To investigate the diagnostic ability of a non-invasive biological marker to predict liver fibrosis in hepatitis C genotype 4 patients with high accuracy. METHODS: A cohort of 332 patients infected with hepatitis C genotype 4 was included in this cross-sectional study. Fasting plasma glucose, insulin, C-peptide, and angiotensin-converting enzyme serum levels were measured. Insulin resistance was mathematically calculated using the homeostasis model of insulin resistance (HOMA-IR)...
November 18, 2016: World Journal of Hepatology
https://www.readbyqxmd.com/read/27904945/-sarcoidosis-and-uveitis-an-update
#17
REVIEW
J G Garweg
Ocular involvement in sarcoidosis is present in up to one third of patients and is frequently manifested before the underlying systemic disease has been diagnosed. With a view to the therapeutic consequences an early diagnosis of the underlying disease is advantageous. In cases of visual loss early diagnostic measures include invasive procedures, such as ultrasound-guided bronchoalveolar lavage and transbronchial biopsy, if nodular conjunctival or cutaneous manifestations which would confirm the diagnosis are not present...
November 30, 2016: Der Ophthalmologe: Zeitschrift der Deutschen Ophthalmologischen Gesellschaft
https://www.readbyqxmd.com/read/27889753/renal-denervation-attenuates-multi-organ-fibrosis-and-improves-vascular-remodeling-in-rats-with-transverse-aortic-constriction-induced-cardiomyopathy
#18
Kai Wang, Dasheng Lu, Bin Zhang, Shengchan Wang, Qian Liu, Qi Zhang, Jie Geng, Qijun Shan
BACKGROUND/AIMS: To investigate the effects of renal denervation (RDN) on multi-organ fibrosis and vascular remodeling in cardiomyopathy. METHODS: Thirty-six male Sprague-Dawley rats underwent transverse aortic constriction (TAC). Five weeks later, 28 surviving TAC rats were randomly assigned to three groups: (1) RDN, (2) Sham, (3) Carvedilol. Six male Sham TAC rats served as the Control. Ten weeks after TAC, samples were collected. RESULTS: TAC rats showed an increased diastolic interventricular septal thickness at week 5...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27879415/the-angiotensin-converting-enzyme-inhibitor-captopril-rescues-mice-from-endotoxin-induced-lethal-hepatitis
#19
Pu Ge, Rong Jiang, Xin Yao, Jing Li, Jie Dai, Li Zhang, Bin Ye
The renin-angiotensin system is classically regarded as a crucial regulator of circulatory homeostasis, but recent studies also revealed its pro-inflammatory roles. The beneficial effects of the angiotensin-converting enzyme inhibitor (ACEI) in severe inflammatory injury in the lung and heart have been previously reported, but its potential effects on lethal hepatitis were unknown. In this study, a mouse model with LPS/d-galactosamine (GalN)-induced fulminant hepatitis were used to test the protective potential of captopril, a representative ACEI...
November 22, 2016: Innate Immunity
https://www.readbyqxmd.com/read/27853271/foetal-programming-by-methyl-donor-deficiency-produces-steato-hepatitis-in-rats-exposed-to-high-fat-diet
#20
Anaïs Bison, Aude Marchal-Bressenot, Zhen Li, Ilef Elamouri, Eva Feigerlova, Lu Peng, Remi Houlgatte, Bernard Beck, Gregory Pourié, Jean-Marc Alberto, Remy Umoret, Guillaume Conroy, Jean-Pierre Bronowicki, Jean-Louis Guéant, Rosa-Maria Guéant-Rodriguez
Non-alcoholic steatohepatitis (NASH) is a manifestation of metabolic syndrome, which emerges as a major public health problem. Deficiency in methyl donors (folate and vitamin B12) during gestation and lactation is frequent in humans and produces foetal programming effects of metabolic syndrome, with small birth weight and liver steatosis at day 21 (d21), in rat pups. We investigated the effects of fetal programming on liver of rats born from deficient mothers (iMDD) and subsequently subjected to normal diet after d21 and high fat diet (HF) after d50...
November 17, 2016: Scientific Reports
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