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Isolated liver perfusion

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https://www.readbyqxmd.com/read/28646428/effects-of-carvacrol-on-survival-mesenteric-blood-flow-aortic-function-and-multiple-organ-injury-in-a-murine-model-of-polymicrobial-sepsis
#1
Erdem Kamil Ozer, Mustafa Tugrul Goktas, Aysun Toker, Hulagu Bariskaner, Ceyhan Ugurluoglu, Alper Bektas Iskit
Carvacrol (CRV) has strong cytoprotective, antioxidant, and anti-inflammatory properties. We aimed to demonstrate the possible protective effects of CRV on survival, mesenteric artery blood flow (MBF), vascular reactivity, and oxidative and inflammatory injuries in a murine model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). Wistar rats were allocated into the following four groups: Sham, CLP, Sham + CRV, and CLP + CRV. The animals were orally administered with CRV (80 mg/kg/day) or vehicle (corn oil; 1 mL/kg/day) for 7 days...
June 23, 2017: Inflammation
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
#2
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 22, 2017: British Journal of Nutrition
https://www.readbyqxmd.com/read/28624444/distribution-lipid-bilayer-affinity-and-kinetics-of-the-metabolic-effects-of-dinoseb-in-the-liver
#3
Gabriela Bueno Franco Salla, Lívia Bracht, Anacharis Babeto de Sá-Nakanishi, Angela Valderrama Parizotto, Fabrício Bracht, Rosane Marina Peralta, Adelar Bracht
Dinoseb is a highly toxic pesticide of the dinitrophenol group. Its use has been restricted, but it can still be found in soils and waters in addition to being a component of related pesticides that, after ingestion by humans or animals, can originate the compound by enzymatic hydrolysis. As most dinitrophenols, dinoseb uncouples oxidative phosphorylation. In this study, distribution, lipid bilayer affinity and kinetics of the metabolic effects of dinoseb were investigated, using mainly the isolated perfused rat liver, but also isolated mitochondria and molecular dynamics simulations...
June 15, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28585911/transplant-of-hepatocytes-undifferentiated-mesenchymal-stem-cells-and-in-vitro-hepatocyte-differentiated-mesenchymal-stem-cells-in-a-chronic-liver-failure-experimental-model-a-comparative-study
#4
Hanan El Baz, Zeinab Demerdash, Manal Kamel, Shimaa Atta, Faten Salah, Salwa Hassan, Olfat Hammam, Heba Khalil, Safa Meshaal, Inas Raafat
OBJECTIVES: Liver transplant is the cornerstone line of treatment for chronic liver diseases; however, the long list of complications and obstacles stand against this operation. Searching for new modalities for treatment of chronic liver illness is a must. In the present research, we aimed to compare the effects of transplant of undifferentiated human mesenchymal stem cells, in vitro differentiated mesenchymal stem cells, and adult hepatocytes in an experimental model of chronic liver failure...
June 5, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28557337/a-reappraisal-of-the-proposed-metabolic-and-antioxidant-actions-of-butylated-hydroxytoluene-bht-in-the-liver
#5
Lorena Dos Santos Castro, Lívia Bracht, Jurandir Fernando Comar, Rosane Marina Peralta, Adelar Bracht
Butylated hydroxytoluene (BHT) was investigated for its metabolic actions in the perfused rat liver. Contrary to what is expected from an uncoupler, BHT up to 500 μM did not stimulate oxygen uptake nor did it inhibit gluconeogenesis from lactate. Transformation of fructose into glucose was also not affected by BHT; only lactate production was slightly increased at the concentration of 100 μM. The uncoupling effect of BHT in isolated mitochondria was confirmed, but only at concentrations above 10 μM; uncoupling at lower concentrations, 10(-9) to 10(-6)  M, could not be confirmed...
May 29, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/28549307/thymoquinone-protects-against-the-sepsis-induced-mortality-mesenteric-hypoperfusion-aortic-dysfunction-and-multiple-organ-damage-in-rats
#6
Erdem Kamil Ozer, Mustafa Tugrul Goktas, Aysun Toker, Sultan Pehlivan, Hulagu Bariskaner, Ceyhan Ugurluoglu, Alper Bektas Iskit
BACKGROUND: Thymoquinone (TQ) is a potent cytoprotective, antioxidant and anti-inflammatory agent. We aimed to investigate the possible protective effects of TQ on survival, mesenteric artery blood flow (MABF), vascular reactivity, oxidative and inflammatory injuries in a murine sepsis model induced by cecal ligation and puncture (CLP). METHODS: Wistar rats were divided into the following four groups: Sham, CLP, Sham+TQ and CLP+TQ. TQ (1mg/kg/day) or vehicle (dimethyl sulfoxide, 1mL/kg/day) was intraperitoneally injected for 3 days...
March 24, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28542705/a-pump-free-microfluidic-3d-perfusion-platform-for-the-efficient-differentiation-of-human-hepatocyte-like-cells
#7
Louis Jun Ye Ong, Lor Huai Chong, Lin Jin, Pawan Kumar Singh, Poh Seng Lee, Hanry Yu, Abhishek Ananthanarayanan, Hwa Liang Leo, Yi-Chin Toh
The practical application of microfluidic liver models for in vitro drug testing is partly hampered by their reliance on human primary hepatocytes, which are limited in number and have batch-to-batch variation. Human stem cell-derived hepatocytes offer an attractive alternative cell source, although their 3D differentiation and maturation in a microfluidic platform have not yet been demonstrated. We develop a pump-free microfluidic 3D perfusion platform to achieve long-term and efficient differentiation of human liver progenitor cells into hepatocyte-like cells (HLCs)...
May 20, 2017: Biotechnology and Bioengineering
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
#8
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/oatp-and-efflux-transporter-mediated-hepatic-uptake-and-biliary-excretion-of-cilostazol-and-its-metabolites-in-rats-and-humans
#9
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
#10
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/28501779/coenzyme-q10-improves-the-survival-mesenteric-perfusion-organs-and-vessel-functions-in-septic-rats
#11
Erdem Kamil Ozer, Mustafa Tugrul Goktas, Ibrahim Kilinc, Sultan Pehlivan, Hulagu Bariskaner, Ceyhan Ugurluoglu, Alper Bektas Iskit
BACKGROUND: Coenzyme Q10 (CoQ10) is a naturally occurring, lipid-soluble antioxidant and an essential electron carrier in the mitochondrial respiratory chain. In sepsis, CoQ10 deficiency induced by mitochondrial failure can lead to hypoxia, hypoperfusion, oxidative organ damage and finally death. We aimed to investigate the effects of CoQ10 on survival, mesenteric artery blood flow (MABF), vascular reactivity, oxidative and inflammatory injuries in cecal ligation and puncture (CLP)-induced sepsis...
July 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28459157/infliximab-alleviates-the-mortality-mesenteric-hypoperfusion-aortic-dysfunction-and-multiple-organ-damage-in-septic-rats
#12
Erdem Kamil Ozer, Mustafa Tugrul Goktas, Ibrahim Kilinc, Aysun Toker, Hulagu Bariskaner, Ceyhan Ugurluoglu, Alper Bektas Iskit
Tumor necrosis factor-alpha (TNF-α) is a pivotal mediator that triggers inflammatory process, oxidative stress and multiple organ injury in sepsis. We investigated the effects of infliximab on survival, mesenteric artery blood flow (MBF), vascular reactivity, oxidative and inflammatory injuries in cecal ligation and puncture (CLP) induced sepsis. Wistar rats were divided into Sham, CLP, Sham+infliximab, CLP+infliximab subgroups. 24 hours before the operations rats were injected intraperitoneally with infliximab (7 mg/kg) or vehicle (saline; 1 mL/kg)...
April 29, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28412881/glutathione-s-transferase-a1-gsta1-as-a-marker-of-acetaminophen-induced-hepatocyte-injury-in-vitro
#13
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
#14
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: While, traditionally, biliverdin and bilirubin are considered end products of heme catabolism, there is evidence for further degradation to diverse bioactive products. As such, 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/28408319/deriving-and-testing-of-dysplastic-murine-hepatocytes-a-new-platform-in-liver-cancer-research
#15
Sharon Pok, Harpreet Vohra, Charbel Wehbe, Vanessa A Barn, Evi Arfianti, Yock-Young Dan, Geoffrey C Farrell, Narci C Teoh
Dysplastic hepatocytes (DH) represent altered hepatocytes with potential for malignant transformation. To date, most research on pathways to hepatocarcinogenesis has focused on use of "hepatoma" cell lines derived from hepatocellular carcinoma (HCC). We describe a novel technique for deriving/culturing DH and demonstrate their utility for functional studies in vitro, compared to primary hepatocytes (PH) and HCC. PH and DH were prepared by portal vein collagenase perfusion from C57BL/6J mice. DH were subsequently subjected to FACS...
April 10, 2017: Experimental Cell Research
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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