Gene Expression and Protein Abundance of Hepatic Drug Metabolizing Enzymes in Liver Pathology
Hepatic drug metabolizing enzymes (DMEs) markedly affect drug pharmacokinetics. Because liver diseases may alter enzymatic function and in turn drug handling and clinical efficacy, we investigated DMEs expression in dependence on liver pathology and liver failure state. In 5 liver pathologies (hepat...
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doaj-5d8fca0e121047dd9394a9be7c6ec67c2021-09-26T00:56:11ZengMDPI AGPharmaceutics1999-49232021-08-01131334133410.3390/pharmaceutics13091334Gene Expression and Protein Abundance of Hepatic Drug Metabolizing Enzymes in Liver PathologyMarek Drozdzik0Joanna Lapczuk-Romanska1Christoph Wenzel2Sylwia Szelag-Pieniek3Mariola Post4Łukasz Skalski5Mateusz Kurzawski6Stefan Oswald7Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, Powstancow Wlkp. 72 Str., 70-111 Szczecin, PolandDepartment of Experimental and Clinical Pharmacology, Pomeranian Medical University, Powstancow Wlkp. 72 Str., 70-111 Szczecin, PolandDepartment of Pharmacology, Center of Drug Absorption and Transport, University Medicine Greifswald, 17489 Greifswald, GermanyDepartment of Experimental and Clinical Pharmacology, Pomeranian Medical University, Powstancow Wlkp. 72 Str., 70-111 Szczecin, PolandDepartment of General and Transplantation Surgery, County Hospital, 70-891 Szczecin, PolandDepartment of Experimental and Clinical Pharmacology, Pomeranian Medical University, Powstancow Wlkp. 72 Str., 70-111 Szczecin, PolandDepartment of Experimental and Clinical Pharmacology, Pomeranian Medical University, Powstancow Wlkp. 72 Str., 70-111 Szczecin, PolandInstitute of Pharmacology and Toxicology, Rostock University Medical Center, 18051 Rostock, GermanyHepatic drug metabolizing enzymes (DMEs) markedly affect drug pharmacokinetics. Because liver diseases may alter enzymatic function and in turn drug handling and clinical efficacy, we investigated DMEs expression in dependence on liver pathology and liver failure state. In 5 liver pathologies (hepatitis C, alcoholic liver disease, autoimmune hepatitis, primary biliary cholangitis and primary sclerosing cholangitis) and for the first time stratified according to the Child–Pugh score, 10 CYPs (CYP1A1, CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4 and CYP3A5) and 4 UGTs (UGT1A1, UGT1A3, UGT2B7 and UGT2B) enzymes were quantified for protein abundance (LC-MS/MS) and gene expression (qRT-PCR). CYP2E1 was the most vulnerable enzyme, and its protein levels were significantly reduced just in Child–Pugh class A livers. The protein abundance of CYP1A1, CYP2B6, CYP2C19, CYP2D6 as well as UGT1A1, UGT1A3 and UGT2B15 was relatively stable in the course of progression of liver function deterioration. Alcoholic liver disease and primary biliary cholangitis were involved in the most prominent changes in the protein abundances, with downregulation of 6 (CYP1A2, CYP2C8, CYP2D6, CYP2E1, CYP3A4, UGT2B7) and 5 (CYP1A1, CYP2B6, CYP2C8, CYP2E1, CYP3A4) significantly downregulated enzymes, respectively. The results of the study demonstrate that DMEs protein abundance is affected both by the type of liver pathology as well as functional state of the organ.https://www.mdpi.com/1999-4923/13/9/1334hepatic pathologyliverdrug metabolizing enzymes |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Marek Drozdzik Joanna Lapczuk-Romanska Christoph Wenzel Sylwia Szelag-Pieniek Mariola Post Łukasz Skalski Mateusz Kurzawski Stefan Oswald |
spellingShingle |
Marek Drozdzik Joanna Lapczuk-Romanska Christoph Wenzel Sylwia Szelag-Pieniek Mariola Post Łukasz Skalski Mateusz Kurzawski Stefan Oswald Gene Expression and Protein Abundance of Hepatic Drug Metabolizing Enzymes in Liver Pathology Pharmaceutics hepatic pathology liver drug metabolizing enzymes |
author_facet |
Marek Drozdzik Joanna Lapczuk-Romanska Christoph Wenzel Sylwia Szelag-Pieniek Mariola Post Łukasz Skalski Mateusz Kurzawski Stefan Oswald |
author_sort |
Marek Drozdzik |
title |
Gene Expression and Protein Abundance of Hepatic Drug Metabolizing Enzymes in Liver Pathology |
title_short |
Gene Expression and Protein Abundance of Hepatic Drug Metabolizing Enzymes in Liver Pathology |
title_full |
Gene Expression and Protein Abundance of Hepatic Drug Metabolizing Enzymes in Liver Pathology |
title_fullStr |
Gene Expression and Protein Abundance of Hepatic Drug Metabolizing Enzymes in Liver Pathology |
title_full_unstemmed |
Gene Expression and Protein Abundance of Hepatic Drug Metabolizing Enzymes in Liver Pathology |
title_sort |
gene expression and protein abundance of hepatic drug metabolizing enzymes in liver pathology |
publisher |
MDPI AG |
series |
Pharmaceutics |
issn |
1999-4923 |
publishDate |
2021-08-01 |
description |
Hepatic drug metabolizing enzymes (DMEs) markedly affect drug pharmacokinetics. Because liver diseases may alter enzymatic function and in turn drug handling and clinical efficacy, we investigated DMEs expression in dependence on liver pathology and liver failure state. In 5 liver pathologies (hepatitis C, alcoholic liver disease, autoimmune hepatitis, primary biliary cholangitis and primary sclerosing cholangitis) and for the first time stratified according to the Child–Pugh score, 10 CYPs (CYP1A1, CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4 and CYP3A5) and 4 UGTs (UGT1A1, UGT1A3, UGT2B7 and UGT2B) enzymes were quantified for protein abundance (LC-MS/MS) and gene expression (qRT-PCR). CYP2E1 was the most vulnerable enzyme, and its protein levels were significantly reduced just in Child–Pugh class A livers. The protein abundance of CYP1A1, CYP2B6, CYP2C19, CYP2D6 as well as UGT1A1, UGT1A3 and UGT2B15 was relatively stable in the course of progression of liver function deterioration. Alcoholic liver disease and primary biliary cholangitis were involved in the most prominent changes in the protein abundances, with downregulation of 6 (CYP1A2, CYP2C8, CYP2D6, CYP2E1, CYP3A4, UGT2B7) and 5 (CYP1A1, CYP2B6, CYP2C8, CYP2E1, CYP3A4) significantly downregulated enzymes, respectively. The results of the study demonstrate that DMEs protein abundance is affected both by the type of liver pathology as well as functional state of the organ. |
topic |
hepatic pathology liver drug metabolizing enzymes |
url |
https://www.mdpi.com/1999-4923/13/9/1334 |
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