Intestinal transporters are crucial determinants in the oral absorption of many drugs. We therefore studied mRNA expression (N = 33) and absolute protein content 10) clinically relevant healthy epithelium duodenum, proximal distal jejunum ileum, ascending, transversal, descending, sigmoidal colon six organ donors (24–54 years). In small intestine, abundance nearly all proteins ranged between 0.2 1.6 pmol/mg with exception those OCT3 (<0.1 pmol/mg) PEPT1 (2.6–4.9 that accounted for ∼50%...

This work revises and complements existing findings on the distribution of drug-metabolizing enzymes in first-pass effect organs. We explored gene expression (quantitative polymerase chain reaction) protein abundance (liquid chromatography/ tandem mass spectrometry) CYP1A2, CYP2B6, CYP2C8/9/19, CYP2D6, CYP2E1, CYP3A4/5, UGT1A1/3, UGT2B7/15 liver, duodenum, jejunum, ileum, colon paired tissues from nine organ donors. All proteins were detected but intestine CYP2C9/19, UGT2B7 found. CYP3A4...

Bioavailability of orally administered drugs is partly determined by function drug transporters in the liver and intestine. Therefore, we explored adenosine triphosphate–binding cassette (ABC) solute carriers family expression (quantitative polymerase chain reaction) protein abundance (liquid chromatography tandem mass spectrometry ( LC ‐ MS / )) human duodenum, jejunum, ileum, colon paired tissue specimens from nine organ donors. The transporter proteins were detected...

The oral bioavailability of many drugs is highly influenced not only by hepatic but also intestinal biotransformation. To estimate the impact phase I and II metabolism on drug absorption, knowledge expression levels respective enzymes an essential prerequisite. In addition, potential interplay transport contributes to disposition. Both mechanisms may be subjected coordinative regulation nuclear receptors, leading unwanted drug-drug interactions due induction transport. Thus, it was aim this...

Transmembrane drug transport in hepatocytes is one of the major determinants pharmacokinetics. In present study, ABC transporters (P-gp, MRP1, MRP2, MRP3, MRP4, BCRP, and BSEP) SLC (MCT1, NTCP, OAT2, OATP1B1, OATP1B3, OATP2B1, OCT1, OCT3) were quantified for protein abundance (LC-MS/MS) mRNA levels (qRT-PCR) hepatitis C virus (HCV)-infected liver samples from Child–Pugh class A (n = 30), B 21), 7) patients. Protein BSEP, MCT1, OCT3 not significantly affected by HCV infection. P-gp, OATP1B3...

New-onset diabetes after transplantation (NODAT) is a major complication kidney transplantation. The risk factors for NODAT include the use of calcineurin inhibitors as part immunosuppressive regimen, among which tacrolimus has most pronounced diabetogenic effect. Both and type 2 mellitus (T2DM) share several factors. Recent studies have identified number common genetic variants associated with increased T2DM. Here we report results our study on potential effect single nucleotide...

Membrane monocarboxylate transporter 1 (SLC16A1/MCT1) plays an important role in hepatocyte homeostasis, as well drug handling. However, there is no available information about the impact of liver pathology on levels and function. The study was aimed to quantify SLC16A1 mRNA (qRT-PCR) MCT1 protein abundance (liquid chromatography–tandem mass spectrometry (LC¬¬–MS/MS)) livers patients diagnosed, according standard clinical criteria, with hepatitis C, primary biliary cirrhosis, sclerosing...

Hepatic drug metabolizing enzymes (DMEs), whose activity may be affected by liver diseases, are major determinants of pharmacokinetics. Hepatitis C samples in different functional states, i.e., the Child-Pugh class A (n = 30), B 21) and 7) were analyzed for protein abundances (LC-MS/MS) mRNA levels (qRT-PCR) 9 CYPs 4 UGTs enzymes. The CYP1A1, CYP2B6, CYP2C8, CYP2C9, CYP2D6 not disease. In livers, a significant up-regulation UGT1A1 (to 163% controls) was observed. associated with...

In this paper, we study synthesis and characteristics of mesoporous silica nanotubes modified by titanium dioxide, as well their antimicrobial properties influence on mitochondrial activity mouse fibroblast L929. Nanocrystalized titania is confined in mesopores its light activated antibacterial response revealed. The analysis the effect Escherichia coli. (ATCC 25922) shows strong enhancement during irradiation with artificial visible ultraviolet respect to commercial catalyst control sample...

Hepatic drug metabolizing enzymes (DMEs) markedly affect pharmacokinetics. Because liver diseases may alter enzymatic function and in turn handling clinical efficacy, we investigated DMEs expression dependence on pathology failure state. In 5 pathologies (hepatitis C, alcoholic disease, autoimmune hepatitis, primary biliary cholangitis sclerosing cholangitis) for the first time stratified according to Child–Pugh score, 10 CYPs (CYP1A1, CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1,...

First pass metabolism by phase I and II enzymes in the intestines liver is a major determinant of oral bioavailability many drugs. Several studies analyzed expressions drug-metabolizing (DMEs), such as CYP3A4 UGT1A1 human gut liver. However, there still lack knowledge regarding other DMEs (i.e., "minor" DMEs), although several clinically relevant drugs are affected those enzymes. Moreover, very limited intra-subject data on hepatic intestinal expression levels minor DMEs. To fill this gap...

Nuclear receptors and transcription factors regulate the functions of many genes involved in cellular physiology pathology (e.g. tumorigenesis autoimmune diseases). The present study was performed to define expression regulation aryl hydrocarbon receptor (AhR), pregnane X ( PXR ), constitutive androstane CAR nuclear factor E2‐related 2 (Nrf2) rat parotid gland. Constitutive expression, as well after stimulation with specific inducers for AhR [2,3,7,8‐tetrachloro‐dibenzylo‐ p‐ dioxin TCDD )],...

Salivary glands provide secretory functions, including secretion of xenobiotics and among them drugs. However, there is no published information about protein abundance drug transporters measured using reliable quantification methods. Therefore, mRNA expression absolute content clinically relevant ABC (n = 6) SLC 15) family member in the human parotid gland, qRT-PCR liquid chromatography‒tandem mass spectrometry (LC-MS/MS) method, were studied. The nearly all proteins ranged between 0.04...

Despite on-going medical advances, ovarian cancer survival rates have stagnated. In order to improve IP delivery of platinum-based antineoplastics, we aimed develop a sustained drug system for carboplatin (CPt). Toward this aim, pursued double emulsion process obtaining CPt-loaded microcapsules composed poly(ethylene terephthalate-ethylene dilinoleate) (PET-DLA) copolymer. We were able obtain PET-DLA microspheres in the targeted size range 10-25 µm (median: 18.5 µm), reduce intraperitoneal...

Hepatic enzymes involved in drug metabolism vary markedly expression, abundance and activity, which affects individual susceptibility to drugs toxicants. The present study aimed compare mRNA expression protein of the most pharmacologically relevant drug-metabolizing two main sources control liver samples that are used as reference, i.e. organ donor livers non-tumorous tissue from metastatic livers. An association analysis common genetic variants with levels was also performed. CYP450 UGT...

Abstract Background Wilson’s disease is a genetic disorder inherited in recessive manner, caused by mutations the copper-transporter ATP7B. Although it well-known disease, currently available treatments are far from satisfactory and their efficacy varies individual patients. Due to lack of information about drug-metabolizing enzymes drug transporters profile livers, we aimed evaluate mRNA expression protein abundance selected this liver disorder. Methods We analyzed gene (qPCR) (LC–MS/MS) 14...

Oral Diseases (2011) 17 , 414–419 Background: The incidence of gingival overgrowth among renal transplant patients treated with cyclosporine A ranges from 13% to 84.6%, and the is not only esthetic but also a medical problem. We studied determination association between TGF ‐β1 ( TGFB1 ) gene polymorphism in kidney medicated cyclosporin A. Methods: Eighty‐four 140 control without were enrolled into case study. was determined using PCR‐RFLP assay for +869T&gt;C codon 10 +915G&gt;C 25 as well...