Protein Abundance of Drug Metabolizing Enzymes in Human Hepatitis C Livers.

Hepatic drug metabolizing enzymes (DMEs), whose activity may be affected by liver diseases, are major determinants of drug pharmacokinetics. Hepatitis C liver samples in different functional states, i.e.

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 ( = 30), B ( = 21), and C ( = 7) patients. Protein levels of BSEP, MRP3, MCT1, OAT2, OATP1B3, and OCT3 were not significantly affected by HCV infection.

The reference liver-CYP450 and UGT enzymes in healthy donor and metastatic livers: the impact of genotype.

Background: Hepatic enzymes involved in drug metabolism vary markedly in expression, abundance and activity, which affects individual susceptibility to drugs and toxicants. The present study aimed to compare mRNA expression and protein abundance of the most pharmacologically relevant drug-metabolizing enzymes in two main sources of the control liver samples that are used as the reference, i.e.

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 (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).

Hepatic drug-metabolizing enzymes and drug transporters in Wilson's disease patients with liver failure.

Background: Wilson'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.

Identifying Differentially Expressed MicroRNAs, Target Genes, and Key Pathways Deregulated in Patients with Liver Diseases.

Liver diseases are important causes of morbidity and mortality worldwide. The aim of this study was to identify differentially expressed microRNAs (miRNAs), target genes, and key pathways as innovative diagnostic biomarkers in liver patients with different pathology and functional state. We determined, using RT-qPCR, the expression of 472 miRNAs in 125 explanted livers from subjects with six different liver pathologies and from control livers.

Monocarboxylate Transporter 1 (MCT1) in Liver Pathology.

Membrane monocarboxylate transporter 1 (/MCT1) plays an important role in hepatocyte homeostasis, as well as drug handling. However, there is no available information about the impact of liver pathology on the transporter levels and function. The study was aimed to quantify mRNA (qRT-PCR) and MCT1 protein abundance (liquid chromatography-tandem mass spectrometry (LC---MS/MS)) in the livers of patients diagnosed, according to the standard clinical criteria, with hepatitis C, primary biliary cirrhosis, primary sclerosing hepatitis, alcoholic liver disease (ALD), and autoimmune hepatitis.

Protein Abundance of Hepatic Drug Transporters in Patients With Different Forms of Liver Damage.

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.

The reference liver - ABC and SLC drug transporters in healthy donor and metastatic livers.

Background: Analysis of results and conclusions in studies dedicated to pathology of the liver are usually based on comparison of pathological liver specimens and control/reference (considered as healthy) tissues. There are two main sources of the control liver samples used as the reference livers, i.e.