ArticlePharmacological reports : PR2021
Hepatic drug-metabolizing enzymes and drug transporters in Wilson's disease patients with liver failure.
Article in Pharmacological reports : PR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 10 citations in OpenAlex.
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- The involvement of miRNAs in CYP450 enzymes and UDP-glucuronosyltransferases regulation in the human liver.Scientific reports · 2026Article
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- Obesity-related drug-metabolizing enzyme expression alterations in the human liver.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Article
- Drug-drug interactions of plant alkaloids derived from herbal medicines on the phase II UGT enzymes: an introductory review.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Astragalus Injection Modulates the Pharmacokinetics of Doxorubicin and CYP450 Enzymes.Current pharmaceutical design · 2025Article
- Effect of Particle Size on Physical Properties, Dissolution, In Vitro Antioxidant Activity, and In Vivo Hepatoprotective Properties ofPharmaceutics · 2024Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundWilson's disease is a genetic disorder inherited in a recessive manner, caused by mutations in the copper-transporter ATP7B. Although it is a well-known disease, currently available treatments are far from satisfactory and their efficacy varies in individual patients. Due to the lack of information about drug-metabolizing enzymes and drug transporters profile in Wilson's disease livers, we aimed to evaluate the mRNA expression and protein abundance of selected enzymes and drug transporters in this liver disorder.
methodsWe analyzed gene expression (qPCR) and protein abundance (LC-MS/MS) of 14 drug-metabolizing enzymes and 16 drug transporters in hepatic tissue from Wilson's disease patients with liver failure (n = 7, Child-Pugh class B and C) and metastatic control livers (n = 20).
resultsIn presented work, we demonstrated a downregulation of majority of CYP450 and UGT enzymes. Gene expression of analyzed enzymes ranged between 18 and 65% compared to control group and significantly lower protein content of CYP1A1, CYP1A2, CYP2C8, CYP2C9, CYP3A4 and CYP3A5 enzymes was observed in Wilson's disease. Moreover, a general decrease in hepatocellular uptake carriers from SLC superfamily (significant at protein level for NTCP and OATP2B1) was observed. As for ABC transporters, the protein abundance of BSEP and MRP2 was significantly lower, while levels of P-gp and MRP4 transporters were significantly higher in Wilson's disease.
conclusionsAltered hepatic expression of drug-metabolizing enzymes and drug transporters in Wilson's disease patients with liver failure may result in changes of drug pharmacokinetics in that group of patients.
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