ArticleInternational journal of molecular sciences2023
A Unique In Vitro Assay to Investigate ABCB4 Transport Function.
Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Applicability of MDR1 Overexpressing Abcb1KO-MDCKII Cell Lines for Investigating In Vitro Species Differences and Brain Penetration Prediction.Pharmaceutics · 2024Article
- Evaluation of ABT-751, a novel anti-mitotic agent able to overcome multi-drug resistance, in melanoma cells.Cancer chemotherapy and pharmacology · 2024Article
- Overcoming Biological Barriers: Importance of Membrane Transporters in Homeostasis, Disease and Disease Treatment.International journal of molecular sciences · 2023Article
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Authors and funding
4 authors.
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Abstract
ABCB4 is almost exclusively expressed in the liver, where it plays an essential role in bile formation by transporting phospholipids into the bile. ABCB4 polymorphisms and deficiencies in humans are associated with a wide spectrum of hepatobiliary disorders, attesting to its crucial physiological function. Inhibition of ABCB4 by drugs may lead to cholestasis and drug-induced liver injury (DILI), although compared with other drug transporters, there are only a few identified substrates and inhibitors of ABCB4. Since ABCB4 shares up to 76% identity and 86% similarity in the amino acid sequence with ABCB1, also known to have common drug substrates and inhibitors, we aimed to develop an ABCB4 expressing Abcb1-knockout MDCKII cell line for transcellular transport assays. This in vitro system allows the screening of ABCB4-specific drug substrates and inhibitors independently of ABCB1 activity. Abcb1KO-MDCKII-ABCB4 cells constitute a reproducible, conclusive, and easy to use assay to study drug interactions with digoxin as a substrate. Screening a set of drugs with different DILI outcomes proved that this assay is applicable to test ABCB4 inhibitory potency. Our results are consistent with prior findings concerning hepatotoxicity causality and provide new insights for identifying drugs as potential ABCB4 inhibitors and substrates.
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