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Protein Abundance of Hepatic Drug Transporters in Patients With Different Forms of Liver Damage
Author(s) -
Drozdzik Marek,
SzelagPieniek Sylwia,
Post Mariola,
Zeair Samir,
Wrzesinski Maciej,
Kurzawski Mateusz,
Prieto Jesus,
Oswald Stefan
Publication year - 2020
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.1717
Subject(s) - multidrug resistance associated protein 2 , transporter , organic anion transporter 1 , coefficient of variation , downregulation and upregulation , medicine , chemistry , biology , endocrinology , biochemistry , atp binding cassette transporter , chromatography , gene
Hepatocellular transporter levels were quantified using quantitative reverse transcription polymerase chain reaction and liquid chromatography–tandem mass spectrometry methods. Liver function deterioration (Child‐Pugh class C) produced significant protein abundance (mean values) increase (to healthy livers) in P‐gp (to 260% (CV (coefficient of variation) 82%)) and MRP4 (CV 230%) (not detected in healthy livers), decrease in MRP2 (to 30% (CV 126%)), NTCP (to 34% (CV 112%)), OCT1 (to 35% (CV 153%)), OATP1B1 (to 46% (CV 73%)), and OATP2B1 (to 27% (CV 230%)), whereas BSEP (CV 99%), MRP3 (CV 106%), OAT2 (CV 97%), OCT3 (CV 113%), and OATP1B3 (CV 144%) remained unchanged. Alcoholic liver disease produced significant protein downregulation of MRP2 (to 30% (CV 134%)), NTCP (to 76% (CV 78%)), OAT2 (to 26% (CV 117%)), OATP1B1 (to 61% (CV 76%)), OATP1B3 (to 79% (CV 160%)), and OATP2B1 (to 73% (CV 90%)) of healthy tissue values. Hepatitis C produced BSEP (to 47% (CV 99%)) and OATP2B1 (to 74% (CV 91%)) protein reduction. Primary biliary cholangitis and primary sclerosing cholangitis demonstrated P‐gp and MRP4 protein upregulation (to 350% (CV 47%) and 287% (CV 38%), respectively). Autoimmune hepatitis revealed P‐gp (to 410% (CV 49%)) and MRP4 (CV 96%) increase, and MRP2 (to 18% (CV 259%)) protein decrease. Drug transporters' protein abundance depends on liver pathology type and its functional state.