The role of the efflux carriers Abcg2 and Abcc2 for the hepatobiliary elimination of benzo[a]pyrene and its metabolites in mice
| Autor: | Albrecht Seidel, Julia Aretz, Ernst Petzinger, Alfonso Lampen, Joachim Geyer, Stefanie Hessel, Jasmin Kranz |
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| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty Abcg2 Metabolic Clearance Rate Pharmacology Toxicology Hepatobiliary Elimination Excretion Mice chemistry.chemical_compound Internal medicine Benzo(a)pyrene medicine ATP Binding Cassette Transporter Subfamily G Member 2 Animals Bile RNA Messenger Lung Carcinogen Mice Knockout biology Myocardium Multidrug resistance-associated protein 2 Brain Biological Transport General Medicine Multidrug Resistance-Associated Protein 2 Endocrinology Liver chemistry Gastric Mucosa Knockout mouse biology.protein Efflux Multidrug Resistance-Associated Proteins |
| Zdroj: | Chemico-Biological Interactions. 224:36-41 |
| ISSN: | 0009-2797 |
| Popis: | The ATP-binding cassette transporters Breast Cancer Resistance Protein (Abcg2) and Multidrug Resistance-associated Protein 2 (Abcc2) play an important role for the hepatobiliary elimination of drugs and toxins as well as their metabolites. Previous in vitro transport studies showed that both transporters are involved in the active efflux of phase II metabolites of carcinogenic benzo[ a ]pyrene (BP), however the role of these carriers in hepatobiliary elimination in vivo is still unknown. In the present study, Abcg2 (−/−) and Abcc2 (−/−) knockout mice were used to elucidate the role of Abcg2 and Abcc2 for the hepatobiliary excretion of BP and its metabolites. After intravenous application of [ 3 H]BP the hepatobiliary excretion was significantly reduced in these mice: whereas wild type mice excreted on average 25.4% of the applied dose into the bile over 90 min, Abcg2 (−/−) knockout mice only excreted 10.7% and Abcc2 (−/−) knockout mice 8.6%. As a consequence, [ 3 H]BP concentrations were in general higher in the plasma and in most of the organs of the Abcg2 and Abcc2 knockout mice. Both transporters may have a protective function for BP-induced carcinogenesis in humans, due to its crucial importance for the hepatobiliary elimination of BP via bile. Subjects with reduced ABCG2 or ABCC2 expression might have higher oral bioavailability for BP due to a reduced excretion and so might be more susceptible to BP-induced carcinogenesis. |
| Databáze: | OpenAIRE |
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