Comparative study of CYP2B1/2 induction and the transport of bilirubin and taurocholate in rat hepatocyte-mono- and hepatocyte-Kupffer cell co-cultures
| Autor: | György Török, Glória László, László Homolya, Attila Bátai-Konczos, Katalin Jemnitz, Enikő Ioja, Mónika Szabó, Zsuzsa Veres |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Lipopolysaccharides Male Taurocholic Acid Kupffer Cells Gadolinium(III) chloride Cell Toxicology Models Biological 03 medical and health sciences chemistry.chemical_compound medicine Animals Drug Interactions Rats Wistar Pharmacology Liver injury Chemistry Kupffer cell Transporter Bilirubin Biological Transport medicine.disease Molecular biology In vitro Coculture Techniques Rats 030104 developmental biology medicine.anatomical_structure Biochemistry Hepatocyte Enzyme Induction Cytochrome P-450 CYP2B1 Steroid Hydroxylases Hepatocytes Metabolic Detoxication Phase I Aryl Hydrocarbon Hydroxylases Chemical and Drug Induced Liver Injury Intracellular |
| Zdroj: | Journal of pharmacological and toxicological methods. 82 |
| ISSN: | 1873-488X |
| Popis: | Introduction Hepatocyte-Kupffer cell (KC) co-cultures represent a promising approach for in vitro modeling of complex interactions between parenchymal and non-parenchymal cells in the liver, responsible for drug-induced liver injury (DILI). In this study we aimed to compare hepatocyte monocultures with hepatocyte-KC co-cultures regarding some basic liver functions associated with the chemical defense system. These pathways involve transporters and enzymes the function of which is highly sensitive towards hepatotoxic events. Methods CYP2B1/2 induction and the biliary and sinusoidal elimination of bilirubin (B) and taurocholate (TC) were studied in rat hepatocyte sandwich cultures compared with rat hepatocyte-KC sandwich co-cultures of 1:0, 6:1, 2:1 and 1:1 cell combinations representing the physiologic and pathologic conditions of the liver. Results KCs decreased phenobarbital inducibility of CYP2B1/2 in a cell ratio dependent manner and activation of KCs by lipopolisacharide (LPS) amplified this effect. Similarly, KCs decreased the transport of B and its glucuronides (BG) in both sinusoidal and canalicular directions resulting in its intracellular accumulation. In contrast, the uptake and the efflux of TC were greater in the co-cultures than in the hepatocyte monocultures. Immuno-labelling of sodium-dependent taurocholate transporter (Ntcp) revealed increased expression of the transporter in the presence of KCs. Discussion Here we presented that KCs have a direct impact on some hepatocyte functions suggesting that the co-culture model may be more suitable for drug related hepatotoxicity studies than hepatocyte monocultures. |
| Databáze: | OpenAIRE |
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