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Isolated liver perfusion

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https://www.readbyqxmd.com/read/28549307/thymoquinone-protects-against-the-sepsis-induced-mortality-mesenteric-hypoperfusion-aortic-dysfunction-and-multiple-organ-damage-in-rats
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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...
May 11, 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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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...
March 15, 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
#14
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
#15
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
https://www.readbyqxmd.com/read/28272754/hyperpolarized-%C3%AE-1-13-c-gluconolactone-as-a-probe-of-the-pentose-phosphate-pathway
#16
Karlos X Moreno, Crystal E Harrison, Matthew E Merritt, Zoltan Kovacs, Craig R Malloy, A Dean Sherry
The pentose phosphate pathway (PPP) is thought to be upregulated in trauma (to produce excess NADPH) and in cancer (to provide ribose for nucleotide biosynthesis), but simple methods for detecting changes in flux through this pathway are not available. MRI of hyperpolarized (13) C-enriched metabolites offers considerable potential as a rapid, non-invasive tool for detecting changes in metabolic fluxes. In this study, hyperpolarized δ-[1-(13) C]gluconolactone was used as a probe to detect flux through the oxidative portion of the pentose phosphate pathway (PPPox ) in isolated perfused mouse livers...
March 8, 2017: NMR in Biomedicine
https://www.readbyqxmd.com/read/28256298/contribution-of-mitochondria-to-injury-of-hepatocytes-and-liver-tissue-by-hyperthermia
#17
Rasa Žūkienė, Zita Naučienė, Giedrė Šilkūnienė, Tomas Vanagas, Antanas Gulbinas, Aurelijus Zimkus, Vida Mildažienė
OBJECTIVE: The aim of this study was to investigate functional changes of liver mitochondria within the experimentally modeled transition zone of radiofrequency ablation and to estimate possible contribution of these changes to the energy status of liver cells and the whole tissue. MATERIALS AND METHODS: Experiments were carried out on mitochondria isolated from the perfused liver and isolated hepatocytes of male Wistar rats. Hyperthermia was induced by changing the temperature of perfusion medium in the range characteristic for the transition zone (38-52°C)...
January 9, 2017: Medicina
https://www.readbyqxmd.com/read/28220319/cfd-assessment-of-the-effect-of-convective-mass-transport-on-the-intracellular-clearance-of-intracellular-triglycerides-in-macrosteatotic-hepatocytes
#18
Gabriel Yarmush, Lucas Santos, Joshua Yarmush, Srivathsan Koundinyan, Mubasher Saleem, Nir I Nativ, Martin L Yarmush, Francois Berthiaume, Timothy J Maguire, Chris Guaghan
Donor livers available to transplant for patients with end-stage liver disease are in severe shortage. One possible avenue to expand the donor pool is to recondition livers that would be otherwise discarded due to excessive fat content. Severely steatotic livers (also known as fatty livers) are highly susceptible to ischemia-reperfusion injury and as a result, primary liver non-function post-transplantation. Prior studies in isolated perfused rat livers suggest that "defatting" may be possible in a timeframe of a few hours; thus, it is conceivable that fatty liver grafts could be recovered by machine perfusion to clear stored fat from the organ prior to transplantation...
February 20, 2017: Biomechanics and Modeling in Mechanobiology
https://www.readbyqxmd.com/read/28188296/effect-of-garlic-gingko-and-st-john-s-wort-extracts-on-the-pharmacokinetics-of-fexofenadine-a-mechanistic-study
#19
Jasmina Turkanovic, Michael B Ward, Jacobus P Gerber, Robert W Milne
The aim of this study was to determine the effects of garlic and ginkgo herbal extracts on the pharmacokinetics of the P-glycoprotein (P-gp)/organic anion-transporting polypeptides (Oatps) substrate fexofenadine. Male rats were dosed orally with garlic (120 mg/kg), ginkgo (17 mg/kg), St. John's wort (SJW; 1000 mg/kg; positive control), or Milli-Q water for 14 days. On day 15, rats either were administered fexofenadine (orally or i.v.), had their livers isolated and perfused with fexofenadine, or had their small intestines divided into four segments (SI-SIV) and analyzed for P-gp and Oatp1a5...
May 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28178721/chemosaturation-with-percutaneous-hepatic-perfusion-in-unresectable-hepatic-metastases
#20
REVIEW
Evan S Glazer, Jonathan S Zager
BACKGROUND: In patients with hepatic metastases from solid-organ malignancies, surgical resection may be a potentially curative option, but it is not possible in most cases. Chemosaturation with percutaneous hepatic perfusion was developed for the management of unresectable metastases to the liver. METHODS: Relevant medical literature was summarized with regard to the outcomes and limitations of chemosaturation with percutaneous hepatic perfusion. RESULTS: Six articles were identified that contained data on 91 individuals who received chemosaturation with percutaneous hepatic perfusion...
January 2017: Cancer Control: Journal of the Moffitt Cancer Center
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