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Rat Liver Slices (rat + liver_slice)

Distribution by Scientific Domains
Life Sciences60%
Medical Sciences40%

Selected Abstracts

Gliotoxin non-selectively induces apoptosis in fibrotic and normal livers

LIVER INTERNATIONAL, Issue 2 2006
Werner I. Hagens
Abstract: Background: Liver fibrosis is the common response to chronic liver injury, ultimately leading to cirrhosis. Several lines of evidence indicate that inducing apoptosis of hepatic stellate cells (HSC) may lead to regression of liver fibrosis. Recently, it was shown that gliotoxin (GTX) induces apoptosis of HSC. However, the clinical use of GTX may be limited because of the lack of cell and tissue specificity, causing a high risk of potentially severe adverse effects. The aim of this study, therefore, was to study the effect of GTX on different cells of the liver. Methods: We used normal and fibrotic precision-cut rat liver slices to study the effect of GTX on the various resident liver cell types. In these slices, the complex cell,cell interactions are preserved, which closely mimics the in vivo situation. Results: GTX exhibited a potent apoptosis-inducing activity in these slices. Both immunohistochemical stainings and real-time mRNA techniques showed that this apoptosis-inducing effect was seen in HSC. However, Kupffer cells and liver endothelial cells were also affected by GTX, whereas hepatocytes were only mildly affected. Conclusions: This study indicates that the apoptosis-inducing strategy to treat liver fibrosis has high potential, but it will be necessary to develop an HSC-specific therapy to prevent adverse effects. [source]

Changes in zinc uptake in response to ascorbic acid and folic acid in rat liver slices under normal and oxidative stress conditions

BIOFACTORS, Issue 1 2007
R.S. Tupe
Abstract Zinc plays a dual role, as an integral part of metabolic machinery and in defense against reactive oxygen species. Hepatocytes are important sites for zinc metabolism for synthesis of zinc metalloproteins and maintaining its homeostasis. However, the factors influencing post absorptive zinc metabolism under normal and oxidative stress (OS) conditions are not well understood. Using rat liver slices, we conducted a series of four in vitro zinc uptake experiments to study influence of ascorbic acid and folic acid in normal and oxidative stress conditions with Zn concentrations representing deficient to excess states (7.7,30.7 millimole/L). Zinc uptakes under OS at these four zinc levels were lower than the normal conditions. Folic acid showed significant inhibitory effect on zinc uptake under both normal and OS conditions in a dose response manner. Nevertheless, dose response of ascorbic acid at four zinc levels indicated its marked enhancing effect under OS condition. Differences in zinc uptake trend lines between the normal and OS conditions for interaction of both the vitamins narrowed down as the zinc levels increased. Our results suggest that folic acid causes inhibitory effect, while ascorbic acid may be protective in OS with reference to zinc uptake. [source]

Expression and regulation of the bile acid transporter, OST, -OST, in rat and human intestine and liver

BIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 5 2009
Ansar A. Khan
Abstract The regulation of the OST, and OST, expression was studied in the rat jejunum, ileum, colon and liver and in human ileum and liver by ligands for the farnesoid X receptor (FXR), pregnane X receptor (PXR), vitamin D receptor (VDR) and glucocorticoid receptor (GR) using precision cut tissue slices. The gradient of protein and mRNA expression in segments of the intestine for rOST, and rOST, paralleled that of rASBT. OST, and OST, mRNA expression, quantified by qRT-PCR, in rat jejunum, ileum, colon and liver, and in human ileum and liver was positively regulated by FXR and GR ligands. In contrast, the VDR ligand, 1,25(OH)2D3 decreased the expression of rOST, -rOST, in rat intestine, but had no effect on human ileum, and rat and human liver slices. Lithocholic acid (LCA) decreased the expression of rOST, and rOST, in rat ileum but induced OST, -OST, expression in rat liver slices, and human ileum and liver slices. The PXR ligand, pregnenolone-16, carbonitrile (PCN) had no effect. This study suggest that, apart from FXR ligands, the OST, and OST, genes are also regulated by VDR and GR ligands and not by PXR ligands. This study show that VDR ligands exerted different effects on OST, -OST, in the rat and human intestine and liver compared with other nuclear receptors, FXR, PXR, and GR, pointing to species- and organ-specific differences in the regulation of OST, -OST, genes. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Microfluidic biochip for the perifusion of precision-cut rat liver slices for metabolism and toxicology studies

BIOTECHNOLOGY & BIOENGINEERING, Issue 1 2010
Paul M. van Midwoud
Abstract Early detection of kinetic, metabolic, and toxicity (ADME-Tox) profiles for new drug candidates is of crucial importance during drug development. This article describes a novel in vitro system for the incubation of precision-cut liver slices (PCLS) under flow conditions, based on a poly(dimethylsiloxane) (PDMS) device containing 25-µL microchambers for integration of the slices. The microdevice is coupled to a perifusion system, which enables a constant delivery of nutrients and oxygen and a continuous removal of waste products. Both a highly controlled incubation environment and high metabolite detection sensitivity could be achieved using microfluidics. Liver slices were viable for at least 24,h in the microdevice. The compound, 7-ethoxycoumarin (7-EC), was chosen to test metabolism, since its metabolism includes both phase I and phase II metabolism and when tested in the conventional well plate system, correlates well with the in vivo situation (De Kanter et al. 2004. Xenobiotica 34(3): 229,241.). The metabolic rate of 7-EC was found to be 214,±,5,pmol/min/mg protein in the microdevice, comparable to well plates, and was constant over time for at least 3,h. This perifusion system better mimics the in vivo situation, and has the potential to significantly contribute to drug metabolism and toxicology studies of novel chemical entities. Biotechnol. Bioeng. 2010;105: 184,194. © 2009 Wiley Periodicals, Inc. [source]