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Bitte verwenden Sie diesen Link, wenn Sie dieses Dokument zitieren oder verlinken wollen: https://nbn-resolving.org/urn:nbn:de:gbv:9-opus-64701

Protein Abundance of Drug Transporters in Human Hepatitis C Livers

  • Transmembrane drug transport in hepatocytes is one of the major determinants of drug pharmacokinetics. In the present study, ABC transporters (P-gp, MRP1, MRP2, MRP3, MRP4, BCRP, and BSEP) and SLC transporters (MCT1, NTCP, OAT2, OATP1B1, OATP1B3, OATP2B1, OCT1, and OCT3) were quantified for protein abundance (LC-MS/MS) and mRNA levels (qRT-PCR) in hepatitis C virus (HCV)-infected liver samples from the Child–Pugh class A (n = 30), B (n = 21), and C (n = 7) patients. Protein levels of BSEP, MRP3, MCT1, OAT2, OATP1B3, and OCT3 were not significantly affected by HCV infection. P-gp, MRP1, BCRP, and OATP1B3 protein abundances were upregulated, whereas those of MRP2, MRP4, NTCP, OATP2B1, and OCT1 were downregulated in all HCV samples. The observed changes started to be seen in the Child–Pugh class A livers, i.e., upregulation of P-gp and MRP1 and downregulation of MRP2, MRP4, BCRP, and OATP1B3. In the case of NTCP, OATP2B1, and OCT1, a decrease in the protein levels was observed in the class B livers. In the class C livers, no other changes were noted than those in the class A and B patients. The results of the study demonstrate that drug transporter protein abundances are affected by the functional state of the liver in hepatitis C patients.

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Metadaten
Author: Marek Droździk, Joanna Lapczuk-Romanska, Christoph Wenzel, Łukasz Skalski, Sylwia Szeląg-Pieniek, Mariola Post, Marta Syczewska, Mateusz Kurzawski, Stefan Oswald
URN:urn:nbn:de:gbv:9-opus-64701
DOI:https://doi.org/10.3390/ijms23147947
ISSN:1422-0067
Parent Title (English):International Journal of Molecular Sciences
Publisher:MDPI
Place of publication:Basel
Editor: Giuliano Ciarimboli
Document Type:Article
Language:English
Date of first Publication:2022/07/19
Release Date:2022/11/16
Tag:Child–Pugh score; cirrhosis; drug transporter; hepatitis C; liquid chromatography-mass spectrometry; liver; protein quantification; real-time PCR
GND Keyword:-
Volume:23
Issue:14
Page Number:13
Faculties:Universitätsmedizin / Institut für Pharmakologie
Licence (German):License LogoCreative Commons - Namensnennung