ArticleDrug metabolism and disposition: the biological fate of chemicals2019
Altered Expression and Function of Hepatic Transporters in a Rodent Model of Polycystic Kidney Disease.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 20 citations in OpenAlex.
- Changes in Protein Expression of Renal Drug Transporters and Drug-Metabolizing Enzymes in Autosomal Dominant Polycystic Kidney Disease Patients.Clinical pharmacology and therapeutics · 2025Article
- Pharmacotherapy in kidney disease: what it takes to move from general guidance to specific recommendations to stratified subgroups of patients - the tale of autosomal dominant polycystic kidney disease (ADPKD).Expert opinion on drug metabolism & toxicology · 2025Review
- Altered bile acid and coproporphyrin-I disposition in patients with autosomal dominant polycystic kidney disease.British journal of clinical pharmacology · 2025Observational
- Tolvaptan safety in autosomal-dominant polycystic kidney disease; a focus on idiosyncratic drug-induced liver injury liabilities.Toxicological sciences : an official journal of the Society of Toxicology · 2025Review
- Hepatic Bile Acid Transporters and Drug-induced Hepatotoxicity.Toxicologic pathology · 2023Review
- Impact of pregnancy related hormones on drug metabolizing enzyme and transport protein concentrations in human hepatocytes.Frontiers in pharmacology · 2022Article
- Quantitative Systems Toxicology Modeling Predicts that Reduced Biliary Efflux Contributes to Tolvaptan Hepatotoxicity.Clinical pharmacology and therapeutics · 2021Article
- Safety Profile of Tolvaptan in the Treatment of Autosomal Dominant Polycystic Kidney Disease.Therapeutics and clinical risk management · 2021Review
- Substantially Increased Plasma Coproporphyrin-I Concentrations Associated With OATP1B1*15 Allele in Japanese General Population.Clinical and translational science · 2021Observational
- Pharmacokinetic and toxicodynamic concepts in idiosyncratic, drug-induced liver injury.Expert opinion on drug metabolism & toxicologyArticle
Corrections and comments
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is a common form of inherited polycystic kidney disease (PKD) and is a leading cause of kidney failure. Fluid-filled cysts develop in the kidneys of patients with ADPKD, and cysts often form in their liver and other organs. Previous data have shown that bile acids are increased in the liver of polycystic kidney (PCK) rats, a rodent model of PKD; these changes may be associated with alterations in liver transporter expression and function. However, the impact of PKD on hepatic transporters has not been characterized. Therefore, this preclinical study was designed to investigate hepatic transporter expression and function in PCK compared with wild-type (WT) Sprague-Dawley rats. Transporter gene expression was measured by quantitative polymerase chain reaction, and protein levels were quantified by Western blot and liquid chromatography-tandem mass spectroscopy (LC-MS/MS)-based proteomic analysis in rat livers. Transporter function was assessed in isolated perfused livers (IPLs), and biliary and hepatic total glutathione content was measured. Protein expression of Mrp2 and Oatp1a4 was decreased 3.0-fold and 2.9-fold, respectively, in PCK rat livers based on Western blot analysis. Proteomic analysis confirmed a decrease in Mrp2 and a decrease in Oatp1a1 expression (PCK/WT ratios, 0.368 ± 0.098 and 0.563 ± 0.038, respectively; mean ± S.D.). The biliary excretion of 5(6)-carboxy-2',7'-dichlorofluorescein, a substrate of Oatp1a1, Mrp2, and Mrp3, was decreased 28-fold in PCK compared with WT rat IPLs. Total glutathione was significantly reduced in the bile of PCK rats. Differences in hepatic transporter expression and function may contribute to altered disposition of Mrp2 and Oatp substrates in PKD.
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