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Isolated Hepatic perfusion

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https://www.readbyqxmd.com/read/28918610/the-role-of-tnf-%C3%AE-in-aflatoxin-b-1-induced-hepatic-toxicity-in-isolated-perfused-rat-liver-model
#1
Kazem Koohi Mohammad, Mahmoud Ghazi-Khansari, Farzad Hayati, Hamid Staji, Morteza Keywanloo, Ebrahim Shahroozian
Aflatoxin B-1 (AFB1) is one of the major mycotoxins causing food contamination. Previous studies have shown that AFB1 can induce carcinogenicity and toxic effects in the isolated perfused rat liver and these effects are associated with its metabolites and peroxidation activity. Here we surveyed whether these pathogenic effects of AFB1 are associated with TNF-α as an inflammatory cytokine in general liver damages. In this study, we used twenty male Wistar rats (250-300 g). Rats were divided into four groups...
July 2017: Acta Medica Iranica
https://www.readbyqxmd.com/read/28836197/mouse-and-rat-models-of-induction-of-hepatic-fibrosis-and-assessment-of-portal-hypertension
#2
Sabine Klein, Robert Schierwagen, Frank Erhard Uschner, Jonel Trebicka
Portal hypertension either develops due to progressive liver fibrosis or is the consequence of vascular liver diseases such as portal vein thrombosis or non-cirrhotic portal hypertension. This chapter focuses on different rodent models of liver fibrosis with portal hypertension and also in few non-cirrhotic portal hypertension models. Importantly, after the development of portal hypertension, the proper assessment of drug effects in the portal and systemic circulation should be discussed. The last part of the chapter is dedicated in these techniques to assess the in vivo hemodynamics and the ex vivo techniques of the isolated liver perfusion and vascular contractility...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28806986/antihyperlipidaemic-and-hepatoprotective-activities-of-acidic-and-enzymatic-hydrolysis-exopolysaccharides-from-pleurotus-eryngii-si-04
#3
Chen Zhang, Juan Li, Jing Wang, Xingling Song, Jianjun Zhang, Shang Wu, Chunlong Hu, Zhiyuan Gong, Le Jia
BACKGROUND: Hyperlipidaemia is the major risk factor contributing to the development and progression of atherosclerosis, fatty liver and cerebrovascular disease. Pleurotus eryngii (P. eryngii) is rich in biologically active components, especially polysaccharides that exhibit various biological activities, including reducing blood lipids. In the present study, three novel polysaccharide types, including exopolysaccharides (EPS), enzymatic EPS (EEPS) and acidic EPS (AEPS) were isolated, and the hypolipidaemic and hepatoprotective effects were investigated to better understand possible hypolipidaemic mechanisms and their hepatoprotective effects...
August 14, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28804981/lipopolysaccharide-inhibits-hepatic-gluconeogenesis-in-rats-the-role-of-immune-cells
#4
Hiroshi Tanaka, Yoshikazu Nishikawa, Toru Fukushima, Ataru Taniguchi, Yoshihito Fujita, Kinsuke Tsuda, Nobuya Inagaki, Masaya Hosokawa
AIMS/INTRODUCTION: Bacterial septicemia has diverse clinical symptoms including severe hypoglycemia. However, sepsis-induced hypoglycemia has not yet been examined in detail. The aim of the present study is to investigate the mechanisms underlying hypoglycemia in sepsis. MATERIALS AND METHODS: We induced endotoxin shock in rats using lipopolysaccharide (LPS). After an intraperitoneal injection of LPS, we measured gluconeogenesis using the pyruvate tolerance test (PTT)...
August 14, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28755970/differences-of-first-pass-effect-in-the-liver-and-intestine-contribute-to-the-stereoselective-pharmacokinetics-of-rhynchophylline-and-isorhynchophylline-epimers-in-rats
#5
Xin Wang, Mei Zheng, Jia Liu, Zhifeng Huang, Yidan Bai, Zhuoying Ren, Ziwen Wang, Yangli Tian, Zhou Qiao, Wenyuan Liu, Feng Feng
ETHNOPHARMACOLOGICAL RELEVANCE: Uncaria rhynchophylla (Miq.) Miq. ex Havil., is a plant species used in traditional Chinese medicine to treat cardiovascular and central nervous system diseases. Rhynchophylline (RIN) and isorhynchophylline (IRN), a pair of epimers, are major alkaloids isolated from U. rhynchophylla and exhibit diverse pharmacological effects. Our previous study demonstrated that the pharmacokinetics of these epimers existed stereoselectivity after oral administration; however, the specific mechanism remains unknown and merits investigation...
July 26, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28752456/isolation-of-kupffer-cells-and-hepatocytes-from-a-single-mouse-liver
#6
Marcela Aparicio-Vergara, Michaela Tencerova, Cecilia Morgantini, Emelie Barreby, Myriam Aouadi
Liver perfusion is a common technique used to isolate parenchymal and non-parenchymal liver cells for in vitro experiments. This method allows hepatic cells to be separated based on their size and weight, by centrifugation using a density gradient. To date, other methods allow the isolation of only one viable hepatic cellular fraction from a single mouse; either parenchymal (hepatocytes) or non-parenchymal cells (i.e., Kupffer cells or hepatic stellate cells). Here, we describe a method to isolate both hepatocytes and Kupffer cells from a single mouse liver, thereby providing the unique advantage of studying different liver cell types that have been isolated from the same organism...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28683350/the-metabolic-effects-of-diuron-in-the-rat-liver
#7
Mellina da Silva Simões, Lívia Bracht, Angela Valderrama Parizotto, Jurandir Fernando Comar, Rosane Marina Peralta, Adelar Bracht
A systematic study on the effects of diuron on the hepatic metabolism was conducted with emphasis on parameters linked to energy metabolism. The experimental system was the isolated perfused rat liver. The results demonstrate that diuron inhibited biosynthesis (gluconeogenesis) and ammonia detoxification, which are dependent of ATP generated within the mitochondria. Conversely, it stimulated glycolysis and fructolysis, which are compensatory phenomena for an inhibited mitochondrial ATP generation. Furthermore, diuron diminished the cellular ATP content under conditions where the mitochondrial respiratory chain was the only source of this compound...
June 27, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28660012/angiotensin-ii-or-epinephrine-hemodynamic-and-metabolic-responses-in-the-liver-of-l-name-induced-hypertension-and-spontaneous-hypertensive-rats
#8
Debora Conte Kimura, Marcia Regina Nagaoka, Durval Rosa Borges, Maria Kouyoumdjian
AIM: To study hepatic vasoconstriction and glucose release induced by angiotensin (Ang)II or Epi in rats with pharmacological hypertension and spontaneously hypertensive rat (SHR). METHODS: Isolated liver perfusion was performed following portal vein and vena cava cannulation; AngII or epinephrine (Epi) was injected in bolus and portal pressure monitored; glucose release was measured in perfusate aliquots. RESULTS: The portal hypertensive response (PHR) and the glucose release induced by AngII of L-NAME were similar to normal rats (WIS)...
June 18, 2017: World Journal of Hepatology
https://www.readbyqxmd.com/read/28659160/inhibition-of-mirtazapine-metabolism-by-ecstasy-mdma-in-isolated-perfused-rat-liver-model
#9
Sanaz Jamshidfar, Yalda H Ardakani, Hoda Lavasani, Mohammadreza Rouini
BACKGROUND: Nowadays MDMA (3,4-methylendioxymethamphetamine), known as ecstasy, is widely abused among the youth because of euphoria induction in acute exposure. However, abusers are predisposed to depression in chronic consumption of this illicit compound. Mirtazapine (MRZ), an antidepressant agent, may be prescribed in MDMA-induced depression. MRZ is extensively metabolized in liver by CYP450 isoenzymes. 8-hydroxymirtazapine (8-OH) is mainly produced by CYP2D6. N-desmethylmirtazapine (NDES) is generated by CYP3A4...
June 28, 2017: Daru: Journal of Faculty of Pharmacy, Tehran University of Medical Sciences
https://www.readbyqxmd.com/read/28637520/citrulline-decreases-hepatic-endotoxin-induced-injury-in-fructose-induced-non-alcoholic-liver-disease-an-ex-vivo-study-in-the-isolated-perfused-rat-liver
#10
Wassila Ouelaa, Prasanthi Jegatheesan, Japhète M'bouyou-Boungou, Christelle Vicente, Samir Nakib, Esther Nubret, Jean-Pascal De Bandt
Steatosis can sensitise the liver to various challenges and favour the development of non-alcoholic fatty liver disease (NAFLD). In this context, fructose feeding promotes endotoxin translocation from the gut, contributing to disease progression via an inflammatory process. Citrulline is protective against fructose-induced NAFLD; we hypothesised that this property might be related to its anti-inflammatory and antioxidative action against endotoxin-induced hepatic injuries. This hypothesis was evaluated in a model of perfused liver isolated from NAFLD rats...
June 2017: British Journal of Nutrition
https://www.readbyqxmd.com/read/28542610/gpr40-partial-agonist-mk-2305-lower-fasting-glucose-in-the-goto-kakizaki-rat-via-suppression-of-endogenous-glucose-production
#11
Corin Miller, Michele J Pachanski, Melissa E Kirkland, Daniel T Kosinski, Joel Mane, Michelle Bunzel, Jin Cao, Sarah Souza, Brande Thomas-Fowlkes, Jerry Di Salvo, Adam B Weinglass, Xiaoyan Li, Robert W Myers, Kevin Knagge, Paul E Carrington, William K Hagmann, Maria E Trujillo
GPR40 (FFA1) is a fatty acid receptor whose activation results in potent glucose lowering and insulinotropic effects in vivo. Several reports illustrate that GPR40 agonists exert glucose lowering in diabetic humans. To assess the mechanisms by which GPR40 partial agonists improve glucose homeostasis, we evaluated the effects of MK-2305, a potent and selective partial GPR40 agonist, in diabetic Goto Kakizaki rats. MK-2305 decreased fasting glucose after acute and chronic treatment. MK-2305-mediated changes in glucose were coupled with increases in plasma insulin during hyperglycemia and glucose challenges but not during fasting, when glucose was normalized...
2017: PloS One
https://www.readbyqxmd.com/read/28535976/organic-anion-transporting-polypeptide-and-efflux-transporter-mediated-hepatic-uptake-and-biliary-excretion-of-cilostazol-and-its-metabolites-in-rats-and-humans
#12
Chong Wang, Xiaokui Huo, Changyuan Wang, Qiang Meng, Zhihao Liu, Pengyuan Sun, Jian Cang, Huijun Sun, Kexin Liu
Cilostazol undergoes extensive liver metabolism. However, the transporter-mediated hepatic disposition of cilostazol remains unknown. The present study was performed to investigate the hepatic uptake and biliary excretion of cilostazol and its metabolites (OPC-13015 and OPC-13213) using rat liver and human transporter-transfected cells in vitro. Cilostazol uptake by rat liver slices and isolated rat hepatocytes exhibited time-, concentration-, and temperature dependency and was decreased by Oatp inhibitors, which suggested that Oatp was involved in the hepatic uptake of cilostazol...
May 20, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28535778/exosomes-from-mesenchymal-stem-cells-induce-the-conversion-of-hepatocytes-into-progenitor-oval-cells
#13
Hao-Hsiang Wu, Oscar K Lee
BACKGROUND: We previously reported that mesenchymal stem cells (MSCs) possess therapeutic effects in a murine model of carbon tetrachloride-induced acute liver failure. In the study, we observed that the majority of repopulated hepatocytes were of recipient origin and were adjacent to transplanted MSCs; only a low percentage of repopulated hepatocytes were from transplanted MSCs. The findings indicate that MSCs guided the formation of new hepatocytes. Exosomes are important messengers for paracrine signaling delivery...
May 23, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28412881/glutathione-s-transferase-a1-gsta1-as-a-marker-of-acetaminophen-induced-hepatocyte-injury-in-vitro
#14
Rui Li, Fangping Liu, Yicong Chang, Xin Ma, Minmin Li, Changwen Li, Chenxi Shi, Jingshan He, Ying Li, Zhi Li, Yuexia Lin, Qing Han, Yulin Zhao, Dening Wang
Acetaminophen (APAP) overdose causes serious hepatocyte injury, and new markers are needed to predict APAP-induced hepatic injury. Glutathione S-transferase A1 (GSTA1) plays a significant role in the metabolism of APAP. Primary mouse hepatocytes were isolated by a two-step perfusion in situ. An APAP-induced hepatocyte injury model was used to characterize GSTA1 in APAP treated cells and determine whether GSTA1 could be a prognostic marker in vitro. A significant increase (p < .05) in GSTA1 in cell culture supernatant was detected at 6 h after APAP treatment, while alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH) showed marked differences (p < ...
May 2, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28412296/impact-of-higher-order-heme-degradation-products-on-hepatic-function-and-hemodynamics
#15
Raphael A Seidel, Thierry Claudel, Franziska A Schleser, Navin K Ojha, Matthias Westerhausen, Sandor Nietzsche, Christoph Sponholz, Frans Cuperus, Sina M Coldewey, Stefan H Heinemann, Georg Pohnert, Michael Trauner, Michael Bauer
BACKGROUND & AIMS: Biliverdin and bilirubin were previously considered end products of heme catabolism; now, however, there is evidence for further degradation to diverse bioactive products. Z-BOX A and Z-BOX B arise upon oxidation with unknown implications for hepatocellular function and integrity. We studied the impact of Z-BOX A and B on hepatic functions and explored their alterations in health and cholestatic conditions. METHODS: Functional implications and mechanisms were investigated in rats, hepatocytic HepG2 and HepaRG cells, human immortalized hepatocytes, and isolated perfused livers...
April 12, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28364696/differential-effects-of-liver-steatosis-on-pharmacokinetic-profile-of-two-closely-related-hepatoselective-no-donors-v-pyrro-no-and-v-proli-no
#16
Kamil Kus, Edyta Kus, Agnieszka Zakrzewska, Wojciech Jawien, Barbara Sitek, Maria Walczak, Stefan Chlopicki
PURPOSE: To analyze the effect of liver steatosis and obesity on pharmacokinetic profile of two structurally-related liver-selective NO-donors - V-PYRRO/NO and V-PROLI/NO. METHODS: C57BL/6 mice were fed control or high-fat diet for 15 weeks to induced liver steatosis and obesity (HFD mice). Pharmacokinetics and renal elimination studies were conducted in vivo following iv dosing of V-PYRRO/NO and V-PROLI/NO (0.03mmol/kg). Hepatic clearance was evaluated ex vivo in the isolated perfused mice liver and in vitro with the use of liver microsomes...
June 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28337244/rat-liver-enzyme-release-depends-on-blood-flow-bearing-physical-forces-acting-in-endothelium-glycocalyx-rather-than-on-liver-damage
#17
Julieta A Díaz-Juárez, Rolando Hernández-Muñoz
We have found selective elevation of serum enzyme activities in rats subjected to partial hepatectomy (PH), apparently controlled by hemodynamic flow-bearing physical forces. Here, we assess the involvement of stretch-sensitive calcium channels and calcium mobilization in isolated livers, after chemical modifications of the endothelial glycocalyx and changing perfusion directionality. Inhibiting in vivo protein synthesis, we found that liver enzyme release is influenced by de novo synthesis of endothelial glycocalyx components, and released enzymes are confined into a liver "pool...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28328586/percutaneous-isolated-hepatic-perfusion-hemodynamic-monitoring-and-goal-directed-anesthetic-management-a-case-report
#18
Oscar Martin-Delgado, Miguel Rodriguez, Andres Lopez, Miguel A Reina, Emilio De Vicente, Yolanda Quijano, Antonio Echenagusia, Juan A Martinez
The percutaneous isolated hepatic perfusion utilizes a venovenous bypass to administer high-dose chemotherapy exclusively in the liver, getting depurated through a hemofilter before returning to the systemic circulation. The hepatic perfusion is managed under general anesthesia and invasive monitoring as a result of very abrupt changes in venous return and vascular resistances because of the isolation of the hepatic territory and absorption of circulating catecholamines by the hemofilter. We report a case in which we describe the technique, physiologic implications, anesthetic, and goal-directed hemodynamic management for this procedure...
June 1, 2017: A & A Case Reports
https://www.readbyqxmd.com/read/28317117/comparative-pharmacokinetic-evaluation-of-lopinavir-and-lopinavir-loaded-solid-lipid-nanoparticles-in-hepatic-impaired-rat-model
#19
Punna Rao Ravi, Rahul Vats
OBJECTIVE: Drug-induced hepatotoxicity is a major cause of concern in patients receiving HIV/TB co-treatment. Lopinavir (LPV), an anti-HIV drug, shows poor plasma exposure due to hepatic first-pass metabolism. In this study, we investigated the effect of hepatotoxicity on pharmacokinetics of free LPV and LPV-loaded solid lipid nanoparticles (LPV SLNs) in male Wistar rats. METHODS: Hepatic impairment model in rats was developed by injecting CCl4 (i.p., 2 ml/kg). Comparative pharmacokinetic (n = 5) and tissue distribution studies (n = 3) were conducted following oral administration (20 mg/kg) of free LPV and LPV SLNs in normal and hepatic impaired rats...
March 19, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28277163/predictions-of-bisphenol-a-hepatic-clearance-in-the-isolated-perfused-rat-liver-iprl-impact-of-albumin-binding-and-of-co-administration-with-naproxen
#20
Sara Bounakta, Michel Bteich, Marc Mantha, Patrick Poulin, Sami Haddad
1. This study aimed (i) to characterise hepatic clearance (CL) of bisphenol A (BPA) and naproxen (NAP) administered alone or in binary mixtures to highlight the influence of a binding to albumin (ALB) using an isolated perfused rat liver (IPRL) system; and (ii) to compare results of prediction algorithms with measured clearance rates. 2. The IPRL system and liver microsomes were used to determine the metabolic constants of BPA and NAP either in the presence or absence of ALB. In this study, the IPRL was used as proxy for the in vivo situation...
March 3, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
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