ArticleDrug metabolism and disposition: the biological fate of chemicals2011
Decreased hepatic breast cancer resistance protein expression and function in multidrug resistance-associated protein 2-deficient (TR⁻) rats.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed, 21 citations in OpenAlex.
- Endogenous Coproporphyrin I and III are Altered in Multidrug Resistance-Associated Protein 2-Deficient (TRJournal of pharmaceutical sciences · 2021Article
- Regulation of hepatic P-gp expression and activity by genistein in rats.Archives of toxicology · 2020Article
- Synergistic Anticancer Effects of Gemcitabine with Pitavastatin on Pancreatic Cancer Cell Line MIA PaCa-2 in vitro and in vivo.Cancer management and research · 2020Article
- Characterization of Liver- and Cancer-type-Organic Anion Transporting Polypeptide (OATP) 1B3 Messenger RNA Expression in Normal and Cancerous Human Tissues.Drug metabolism letters · 2018Article
- Pitavastatin suppressed liver cancer cells in vitro and in vivo.OncoTargets and therapy · 2016Article
- An experimental approach to evaluate the impact of impaired transport function on hepatobiliary drug disposition using Mrp2-deficient TR- rat sandwich-cultured hepatocytes in combination with Bcrp knockdown.Molecular pharmaceutics · 2014Article
- Bioavailability and pharmacokinetics of genistein: mechanistic studies on its ADME.Anti-cancer agents in medicinal chemistry · 2012Review
- Placental and fetal disposition of mercuric ions in rats exposed to methylmercury: role of Mrp2.Reproductive toxicology (Elmsford, N.Y.) · 2012Article
- A perspective on efflux transport proteins in the liver.Clinical pharmacology and therapeutics · 2012Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Multidrug resistance-associated protein (Mrp) 2-deficient (TR(-)) Wistar rats have been used to elucidate the role of Mrp2 in drug disposition. Decreased breast cancer resistance protein (Bcrp) levels were reported in sandwich-cultured hepatocytes (SCH) from TR(-) rats compared with those from wild-type (WT) rats. This study was designed to characterize hepatic Bcrp expression and function in TR(-) rats, using nitrofurantoin and pitavastatin as substrates. Bcrp was knocked down by RNA interference in rat SCH. Antibody BXP53, but not BXP21, specifically detected Bcrp knockdown in SCH. Bcrp protein levels were decreased markedly in TR(-) but not Mrp2-deficient Sprague-Dawley [Eisai hyperbilirubinemic rats (EHBR)] rats. Bcrp mRNA levels were decreased significantly in TR(-) livers as determined by TaqMan real-time reverse transcriptase-polymerase chain reaction. Biliary excretion of nitrofurantoin, a specific Bcrp substrate, was decreased significantly in SCH and isolated perfused livers from TR(-) rats compared with those from WT controls, indicating that hepatic Bcrp function is decreased in TR(-) rats. In Bcrp knockdown SCH, the biliary excretion index and in vitro biliary clearance of pitavastatin were decreased significantly to ∼ 58 and ∼ 52% of control, respectively, indicating that Bcrp plays a role in pitavastatin biliary excretion. Pitavastatin biliary excretion was decreased significantly in perfused livers from TR(-) compared with those from WT rats. In conclusion, expression and function of hepatic Bcrp are decreased significantly in TR(-) rats. The potential role of both Bcrp and Mrp2 should be considered when data generated in TR(-) rats are interpreted. TR(-) and EHBR rats in combination may be useful in differentiating the role of Mrp2 and Bcrp in drug/metabolite disposition.
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