{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:19:11Z","timestamp":1790533151656,"version":"4.1.0"},"reference-count":30,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,8,25]],"date-time":"2021-08-25T00:00:00Z","timestamp":1629849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Centre, Cracow, Poland","award":["UMO-2020\/37\/B\/NZ7\/01466"],"award-info":[{"award-number":["UMO-2020\/37\/B\/NZ7\/01466"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>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\u2013Pugh 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\u2013Pugh 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.<\/jats:p>","DOI":"10.3390\/pharmaceutics13091334","type":"journal-article","created":{"date-parts":[[2021,8,25]],"date-time":"2021-08-25T23:25:50Z","timestamp":1629933950000},"page":"1334","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Gene Expression and Protein Abundance of Hepatic Drug Metabolizing Enzymes in Liver Pathology"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6191-7168","authenticated-orcid":false,"given":"Marek","family":"Drozdzik","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, Powstancow Wlkp. 72 Str., 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2027-0687","authenticated-orcid":false,"given":"Joanna","family":"Lapczuk-Romanska","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, Powstancow Wlkp. 72 Str., 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4361-7575","authenticated-orcid":false,"given":"Christoph","family":"Wenzel","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Center of Drug Absorption and Transport, University Medicine Greifswald, 17489 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylwia","family":"Szelag-Pieniek","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, Powstancow Wlkp. 72 Str., 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariola","family":"Post","sequence":"additional","affiliation":[{"name":"Department of General and Transplantation Surgery, County Hospital, 70-891 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0141ukasz","family":"Skalski","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, Powstancow Wlkp. 72 Str., 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4293-7788","authenticated-orcid":false,"given":"Mateusz","family":"Kurzawski","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, Powstancow Wlkp. 72 Str., 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Oswald","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, Rostock University Medical Center, 18051 Rostock, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.clpt.2006.05.006","article-title":"Liver disease selectively modulates cytochrome P450-mediated metabolism","volume":"80","author":"Frye","year":"2006","journal-title":"Clin. 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