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| http://dx.doi.org/10.1155/2010/954639 | DOI Listing |
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Role of Nuclear Receptors PXR and CAR in Xenobiotic-Induced Hepatocyte Proliferation and Chemical Carcinogenesis.
Biol Pharm Bull
January 2020
Laboratory of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka.
Nuclear receptors pregnane X receptor (PXR) and constitutive active/androstane receptor (CAR) are xenobiotic-responsible transcriptional factors that belong to the same subfamily and are expressed abundantly in the liver. They play crucial roles in various liver functions including xenobiotic disposition and energy metabolism. CAR is also involved in xenobiotic-induced hepatocyte proliferation and hepatocarcinogenesis in rodents.
View Article and Find Full Text PDFPXR: Structure-specific activation by hepatotoxic pyrrolizidine alkaloids.
Chem Biol Interact
May 2018
German Federal Institute for Risk Assessment, Department of Food Safety, Max-Dohrn-Str. 8-10, 10589 Berlin, Germany. Electronic address:
Pyrrolizidine alkaloids (PAs) comprise a large group of more than 660 secondary metabolites found in more than 6000 plant species worldwide. Acute PA intoxication induces severe liver damage. Chronic exposure to sub-lethal doses may cause cumulative damage or cancer.
View Article and Find Full Text PDFRegulation of Drug Metabolism by the Interplay of Inflammatory Signaling, Steatosis, and Xeno-Sensing Receptors in HepaRG Cells.
Drug Metab Dispos
April 2018
German Federal Institute for Risk Assessment, Department Food Safety, Berlin (N.T., L.K., C.L., L.B., A.L., A.B.), and Dr. Margarete Fischer-Bosch-Institute for Clinical Pharmacology, Stuttgart (M.T., U.H., U.M.Z.), Germany
Nonalcoholic fatty liver disease (NAFLD), which is characterized by triglyceride deposition in hepatocytes resulting from imbalanced lipid homeostasis, is of increasing concern in Western countries, along with progression to nonalcoholic steatohepatitis (NASH), liver fibrosis, and cirrhosis. Previous studies suggest a complex, mutual influence of hepatic fat accumulation, NASH-related inflammatory mediators, and drug-sensing receptors regulating xenobiotic metabolism. Here, we investigated the suitability of human HepaRG hepatocarcinoma cells as a model for NAFLD and NASH.
View Article and Find Full Text PDFActivation of nuclear receptor CAR by an environmental pollutant perfluorooctanoic acid.
Arch Toxicol
June 2017
Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aramaki-Aoba, Aoba-ku, Sendai, 980-8578, Japan.
Perfluorocarboxylic acids (PFCAs) including perfluorooctanoic acid (PFOA) are environmental pollutants showing high accumulation, thermochemical stability and hepatocarcinogenicity. Peroxisome proliferator-activated receptor α is suggested to mediate their toxicities, but the precise mechanism remains unclear. Previous reports also imply a possible role of constitutive androstane receptor (CAR), a key transcription factor for the xenobiotic-induced expression of various genes involved in drug metabolism and disposition as well as hepatocarcinogenesis.
View Article and Find Full Text PDFTime and dose-dependent effects of phenobarbital on the rat liver miRNAome.
Toxicology
December 2013
Surgery and Cancer, Imperial College London, SW72AZ, UK; Department of Cytogenetics and Genomics, Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus.
In a previous study we had shown that treatment of male Fischer rats with exogenous chemicals for three months resulted in prominent, mode-of-action dependent effects on liver microRNA (miRNA) (Koufaris et al., 2012). Here we investigated how the effects of chemicals on liver miRNA in male Fischer rats relate to the length and dose of exposure to phenobarbital (PB), a drug with multiple established hepatic effects.
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