Morphological and electrophysiological changes of peripheral nerve-muscle unit in the aged rat prevented by levocarnitine acetyl.

The effects of levocarnitine acetyl on structure and function of the sciatic nerve and neuromuscular junctions of the soleus and extensor digitorum longus muscles were studied in the aged rat. To that end, neuromuscular conduction velocity (NMCV) was measured in vivo and morphological and morphometric evaluations were performed. Treatment with levocarnitine acetyl, 150 mg/kg day for six months, restored NMCV values to the levels measured in the young rat; significantly reduced the number of degenerating elements; and increased the number of myelinated fibres having normal structural features. In the soleus and extensor digitorum longus muscles, levocarnitine acetyl increased the complexity of neuromuscular junctions. These experimental findings suggest a neurotrophic action of levocarnitine acetyl on the peripheral nervous system that might have therapeutical applications in age-related peripheral nerve changes.     

Ritonavir induces P-glycoprotein expression, multidrug resistance-associated protein (MRP1) expression, and drug transporter-mediated activity in a human intestinal cell line.

The present study characterized the response of P-glycoprotein (P-gp) and multidrug resistance-associated protein (MRP1) to chronic ritonavir (RIT) exposure by assessing increases in P-gp and MRP1 protein expression and activity. LS-180V intestinal carcinoma cells were exposed for 3 days to 1-100 microM RIT concurrently with controls. P-gp and MRP1 protein was quantified by Western blot analysis. Cell accumulation assays, using the P-gp substrate rhodamine 123 (RH123), the P-gp/MRP1 substrate doxorubicin (DOX), and the MRP substrate carboxyfluorescein (CBF), were performed as a measure of transporter activity. RIT strongly induced P-gp and MRP1 expression (maximum 6-fold and 3-fold increases, respectively) in a concentration-dependent fashion. Following extended exposure to RIT (> 10 microM), cells accumulated < 50% of the RH123 and DOX compared with controls, whereas accumulation of CBF was decreased by 30% at 30 microM. Differences in cell accumulation of RH123 could be eliminated with verapamil (100 microM; a P-gp inhibitor), whereas decreased DOX cell accumulation was only partially reversed by verapamil. Indomethacin (100 microM; an MRP1 inhibitor) had no significant effect on RH123 or DOX accumulation, suggesting limited MRP1-mediated activity. Thus, RIT induced protein expression of P-gp and MRP1 and increased cellular drug exclusion of RH123, DOX, and CBF. Similar in vivo phenomena may occur during anti-HIV drug therapy, explaining potential decrements in therapeutic efficacy due to decreases in bioavailability or alterations in drug distribution.     

Multidrug resistance associated proteins as determining factors of pharmacokinetics and pharmacodynamics of drugs

The multidrug resistance associated proteins (MRP1, MRP2, MRP3, MRP4, MRP5, MRP6, MRP7, MRP8 and MRP9) belong to the ATP-binding cassette superfamily (ABCC family) of transporters. They are expressed differentially in the liver, kidney, intestine, brain and other tissues. These transporters are localized to the apical and/or basolateral membrane of the hepatocytes, enterocytes, renal proximal tubule cells and endothelial cells of the blood-brain barrier. Several MRPs (mainly MRP1-3) are associated with tumor resistance which is often caused by an increased efflux and decreased intracellular accumulation of natural product anticancer drugs and other anticancer agents. MRPs transport a structurally diverse array of important endogenous substances and xenobiotics and their metabolites (in particular conjugates) with different substrate specificity and transport kinetics. Most MRPs are subject to induction and inhibition by a variety of compounds. Several nuclear receptors, including pregnane X receptor (PXR), liver X receptor (LXR), and farnesoid receptor (FXR) participate in the regulation of MRPs. MRPs play an important role in the absorption, distribution and elimination of various drugs in the body and thus may affect their efficacy and toxicity and cause drug-drug interactions. MRPs located in the blood-brain barrier can restrict the penetration of compounds into the central nervous system. Mutation of MRP2 causes Dubin-Johnson syndrome, while mutations in MRP6 are responsible for pseudoxanthoma elasticum. More recently, mutations in mouse Mrp6/Abcc6 gene is associated with dystrophic cardiac calcification (DCC), a disease characterized by hydroxyapatite deposition in necrotic myocytes. A single nucleotide polymorphism, 538G>A in the MRP8/ABCC11 gene, is responsible for determination of earwax type. A better understanding of the function and regulating mechanism of MRPs can help minimize and avoid drug toxicity, unfavourable drug-drug interactions, and to overcome drug resistance.     

Endogenous bile acid disposition in rat and human sandwich-cultured hepatocytes

We hypothesized that flavonoid-induced glutathione (GSH) efflux through multi-drug resistance proteins (MRPs) and subsequent intracellular GSH depletion is a viable mechanism to sensitize cancer cells to chemotherapies. This concept was demonstrated using chrysin (5-25 μM) induced GSH efflux in human non-small cell lung cancer lines exposed to the chemotherapeutic agent, doxorubicin (DOX). Treatment with chrysin resulted in significant and sustained intracellular GSH depletion and the GSH enzyme network in the four cancer cell types was predictive of the severity of chrysin induced intracellular GSH depletion. Gene expression data indicated a positive correlation between basal MRP1, MRP3 and MRP5 expression and total GSH efflux before and after chrysin exposure. Co-treating the cells for 72 h with chrysin (5-30 μM) and DOX (0.025-3.0 μM) significantly enhanced the sensitivity of the cells to DOX as compared to 72-hour DOX alone treatment in all four cell lines. The maximum decrease in the IC₅₀ values of cells treated with DOX alone compared to co-treatment with chrysin and DOX was 43% in A549 cells, 47% in H157 and H1975 cells and 78% in H460 cells. Chrysin worked synergistically with DOX to induce cancer cell death. This approach could allow for use of lower concentrations and/or sensitize cancer cells to drugs that are typically resistant to therapy.     

Cytotoxicity and apoptotic gene expression in an in vitro model of the blood–brain barrier following exposure to poly(butylcyanoacrylate) nanoparticles

Background Poly(butylcyanoacrylate) (PBCA) nanoparticles (NPs) loaded with doxorubicin (DOX) and coated with polysorbate 80 (PS80) have shown efficacy in the treatment of rat glioblastoma. However, cytotoxicity of this treatment remains unclear.

Purpose The purpose of this study was to investigate cytotoxicity and apoptotic gene expression using a proven in vitro co-culture model of the blood–brain barrier.

Methods The co-cultures were exposed to uncoated PBCA NPs, PBCA-PS80 NPs or PBCA-PS80-DOX NPs at varying concentrations and evaluated using a resazurin-based cytotoxicity assay and an 84-gene apoptosis RT-PCR array.

Results The cytotoxicity assays showed PBCA-PS80-DOX NPs exhibited a decrease in metabolic function at lower concentrations than uncoated PBCA NPs and PBCA-PS80 NPs. The apoptosis arrays showed differential expression of 18 genes in PBCA-PS80-DOX treated cells compared to the untreated control.

Discussion As expected, the cytotoxicity assays demonstrated enhanced dose-dependent toxicity in the DOX loaded NPs. The differentially expressed apoptotic genes participate in both the tumor necrosis factor receptor-1 and mitochondria-associated apoptotic pathways implicated in current DOX chemotherapeutic toxicity.

Conclusion The following data suggest that the cytotoxic effect may be attributed to DOX and not the NPs themselves, further supporting the use of PBCA-PS80 NPs as an effective drug delivery vehicle for treating central nervous system conditions.     

Moral reasoning perspectives of community pharmacists in situations of drug shortages

BackgroundDrug shortages affect health systems worldwide. Research in community pharmacy has focused on the nature, extent and impact of these shortages on patients and pharmacists. However, pharmacists’ moral reasoning in situations of drug shortages has not been addressed.ObjectiveTo explore the moral reasoning perspectives of Dutch community pharmacists in situations of drug shortages.MethodAn electronic survey was developed around three drug shortage scenarios with a varying impact on patient outcomes: a Contraceptive, a Parkinson's and an Osteoporosis scenario. Pharmacists rated the likelihood of nine handling options and rated and ranked 13 considerations that may have played a role therein. The considerations represented three moral reasoning perspectives (MRPs): a business orientation (BO), a rules and regulations (RR), and a professional ethics (PE) MRP. Principle component analysis (PCA) was used to investigate construct validity of the MRPs. MRP rating and MRP ranking scores measured the relative importance of the different MRPs of pharmacists in the three shortages.ResultsResults from 267 Pharmacists were obtained. They reported mostly similar handling in the three shortages, except for the likelihood to make agreements with prescribers or other pharmacists and regarding the decision to import a product. The PCA analysis confirmed the three MRPs that accounted for 29% of variance in the data. Both the MRP rating and especially the MRP ranking scores indicated that PE-MRP considerations were most influential on pharmacists' intended handling of the shortages. In the Contraceptive and the Osteoporosis scenarios, the relative importance of a BO-MRP was higher than in the Parkinson's scenario.ConclusionPharmacists predominantly reason with a PE-MRP when handling drug shortages. However, this perspective can be compromised when the drug shortage is perceived to have a lower impact on patient outcomes and when alternative drugs or therapy are expensive.     

The Effect of Diphenylamine-2-carboxylate on C1− Channel Conductance and on Excitability Characteristics of Rat Skeletal Muscle

Abstract— The effect of diphenylamine-2-carboxylate (DPC), a blocker of the C1^? conductive pathway in C1^? transporting epithelia, has been evaluated in-vitro on the electrophysiological variables of rat extensor digitorum longus muscle fibres. DPC (5–240 μM) caused a dose-related increase of membrane resistance which was attributed entirely to a fall in C1^? channel conductance (IC50, 120 μM), since potassium conductance was not affected by the treatment. DPC also modified fibre excitability. A significant dose-dependent increase was observed in the latency of the action potential and in the excitability of the membrane. DPC was less potent on striated fibres than anthracene-9-carboxylic acid, another specific blocker of C1^? channel conductance. Moreover DPC was less potent on skeletal muscle than on C1^? transporting epithelia. Morphological differences in the C1^? channels or of the drug binding sites may account for the differences between tissues.     

Evaluation of transport of common antiepileptic drugs by human multidrug resistance-associated proteins (MRP1, 2 and 5) that are overexpressed in pharmacoresistant epilepsy

Resistance to antiepileptic drugs (AEDs) is one of the most serious problems in the treatment of epilepsy. Accumulating experimental evidence suggests that increased expression of the drug efflux transporter P-glycoprotein (Pgp) at the blood-brain barrier may be involved in the mechanisms leading to AED resistance. In addition to Pgp, increased expression of several multidrug resistance-associated proteins (MRPs) has been determined in epileptogenic brain regions of patients with pharmacoresistant epilepsy. However, it is not known whether AEDs are substrates for MRPs. In the present experiments, we evaluated whether common AEDs are transported by human MRPs (MRP1, 2 and 5) that are overexpressed in AED resistant epilepsy. For this purpose, we used a highly sensitive assay (concentration equilibrium transport assay; CETA) in polarized kidney cell lines (LLC, MDCKII) transfected with human MRPs. The assay was validated by known MRP substrates, including calcein-AM (MRP1), vinblastine (MRP2) and chloromethylfluorescein diacetate (CMFDA; MRP5). The directional transport determined with these drugs in MRP-transfected cell lines could be blocked with the MRP inhibitor MK571. However, in contrast to transport of known MRP substrates, none of the common AEDs (carbamazepine, valproate, levetiracetam, phenytoin, lamotrigine and phenobarbital) used in this study was transported by MRP1, MRP2 or MRP5. A basolateral-to-apical transport of valproate, which could be inhibited by MK571 and probenecid, was determined in LLC cells (both wildtype and transfected), but the specific transporter involved was not identified. The data indicate that common AEDs are not substrates for human MRP1, MRP2 or MRP5, at least in the in vitro models used in this study.     

Expression of Multidrug Resistance-Associated Protein (MRP) in Human Retinal Pigment Epithelial Cells and Its Interaction with BAPSG,a Novel Aldose Reductase Inhibitor

Purpose. The objective of this study was to determine the expression and activity of multidrug resistance–associated protein (MRP) in the retinal pigment epithelial (RPE) cells and to further assess whether BAPSG, a novel anionic aldose reductase inhibitor, interacts with MRP. Methods. Functional and biochemical evidence for MRP was obtained in a human retinal pigment epithelial (ARPE–19) cell line and primary cultures of human retinal pigment epithelial (HRPE) cells. Fluorescein accumulation and efflux in the presence and absence of MRP inhibitors was used to obtain functional evidence for MRP. Western blots and RT–PCR were used to obtain biochemical evidence for MRP1. The influence of MRP inhibitors on BAPSG accumulation and efflux in ARPE–19 cells was determined to understand its interaction with MRP. Results. MRP inhibitors increased fluorescein accumulation and reduced efflux in RPE cells. Both cell types exhibited a 190–kDa western blot band corresponding to MRP1 protein and a 287 bp RT–PCR band corresponding to MRP1 mRNA. MRP inhibitors reduced BAPSG efflux and increased its accumulation in ARPE–19 cells. Conclusions. MRP is functionally and biochemically active in human RPE cells. Anionic BAPSG is a likely substrate for MRP.     

Effect of hindlimb suspension and clenbuterol treatment on polyamine levels in skeletal muscle

Polyamines are unbiquitous, naturally occurring small aliphatic, polycationic, endogenous compounds. They are involved in many cellular processes and may serve as secondary or tertiary messengers to hormonal regulation. The relationship of polyamines and skeletal muscle mass of adductor longus, extensor digitorum longus, and gastrocnemius under unloading (hindlimb suspension) conditions was investigated. Unloading significantly affected skeletal muscle polyamine levels in a fiber-type-specific fashion. Under loading conditions, clenbuterol treatment increased all polyamine levels, whereas under unloading conditions, only the spermidine levels were consistently increased. Unloading attenuated the anabolic effects of clenbuterol in predominately slow-twitch muscles (adductor longus), but had little impact on clenbuterol's action as a countermeasure in fast- twitch muscles such as the extensor digitorum longus. Spermidine appeared to be the primary polyamine involved in skeletal muscle atrophy/hypertrophy.     

Tissue distribution and hepatic and renal ontogeny of the multidrug resistance-associated protein (Mrp) family in mice.

Analysis of the mouse genome has revealed eight multidrug resistance-associated (Mrp) transporters, with mouse homologs for all human MRPs except MRP8. Whereas MRP expression in tissues of humans and rats has been examined, no characterization exists for mice. Furthermore, the ontogeny of mouse Mrps is unknown, and such knowledge may be helpful in understanding age-related pharmacokinetics. Therefore, the purpose of this study was to quantitatively determine 1) expression of the Mrp family in 12 different tissues, 2) gender variations in Mrp expression in liver and kidney, and 3) whether Mrp expression is altered during development. Highest expression of the Mrp family members is as follows: Mrp1 in testes, ovary, and placenta; Mrp2 in intestine, followed by liver and kidney; Mrp3 in large intestine; Mrp4 in kidney; Mrp5 in brain, followed by lung and stomach; Mrp6 in liver; Mrp7 in testes, intestine, and kidney; and Mrp9 solely in testes. Gender differences in Mrp expression were observed: Mrp1, 3, and 4 in kidney, as well as Mrp1 and 4 in liver were female-predominant. Ontogeny of the four Mrps expressed in liver was as follows: Mrp2 and Mrp4 were expressed at adult levels at birth; Mrp3 reached adult levels at day 30, and Mrp6 was not expressed until day 10. In kidney, Mrp1 and Mrp5 were expressed at adult levels at birth, whereas Mrp2, 3, 4, and 6 generally increased over time. In conclusion, marked differences in expression of the individual Mrp family members exist in various tissues, with age, and with gender.     

MRP class of human ATP binding cassette (ABC) transporters: historical background and new research directions

1.?The adenosine triphosphate (ATP) binding cassette (ABC) transporters form one of the largest protein families encoded in the human genome, and more than 48 genes encoding human ABC transporters have been identified and sequenced. It has been reported that mutations of ABC protein genes are causative in several genetic disorders in humans.

2.?Many human ABC transporters are involved in membrane transport of drugs, xenobiotics, endogenous substances or ions, thereby exhibiting a wide spectrum of biological functions. According to the new nomenclature of human ABC transporter genes, the ‘ABCC’ gene sub-family comprises three classes involving multidrug resistance-associated proteins (MRPs), sulfonylurea receptors (SURs), and a cystic fibrosis transmembrane conductance regulator (CFTR).

3.?Molecular cloning studies have identified a total of ten members of the human MRP class including ABCC11, ABCC12, and ABCC13 (pseudo-gene) that have recently been characterized.

4.?This review addresses the historical background and discovery of the ATP-driven xenobiotic export pumps (GS-X pumps) encoded by MRP genes, biological functions of ABC transporters belonging to the MRP class, and regulation of gene expression of MRPs by oxidative stress.     

Identifying medication-related problems in pharmacist-run home visits

BackgroundHome visits (HVs) may be warranted for many reasons (e.g., uncontrolled disease states, suspected psychosocial issues, frequent hospitalizations, poor health literacy). Patients who frequently visit the emergency department (ED) are high-risk individuals, oftentimes exhibiting health-related barriers and medication-related problems (MRPs).ObjectivesThis study seeks to answer whether HVs for frequent ED users conducted by a pharmacist with pharmacy students will detect more MRPs compared to office visits (OVs) and enhance patient perception of HV services.MethodsPatients who visited the ED at least twice over a 12-month period were included in a retrospective chart review. Eligible patients were randomized into an HV group or OV group. Patients in the HV group were visited by a pharmacist and pharmacy students to identify and resolve MRPs, whereas patients in the OV arm brought their medications into the office for review. Patients in the HV group completed a pre- and postvisit survey about their experiences.ResultsEighteen patients participated in the study: 10 patients were randomized to the OV arm and 8 patients were randomized to the HV arm. A total of 39 MRPs were identified in 8 HVs versus 33 MRPs in 10 OVs (mean 5 ± 0.926 vs. 3.3 ± 1.89, P = 0.034). Overall, nonadherence was the most common MRP and medication reconciliation was the most common intervention. All 8 HV patients completed the pre- and post-HV surveys. Post-HV survey results indicated that patients agreed that student pharmacists were professional team members and that their HV was needed. The patients agreed to recommend a pharmacist-run HV.ConclusionPatient homes serve as alternative and convenient spaces for pharmacists to help manage their medications, specifically to identify MRPs and provide meaningful recommendations.     

Effect of Probenecid on Fluorescein Transport in the Central Nervous System Using In Vitro and In Vivo Models

Purpose. The purpose of this study was to characterize the function of multidrug resistance-associated proteins (MRPs) (or MRP-like organic anion transport systems) in the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB) using both an in vitro BBB model and an in vivo microdialysis model.Methods. In vitro functional studies were performed using bovine brain microvessel endothelial cells (BBMEC). The accumulation of fluorescein, an anionic fluorescent dye, in BBMEC was determined with and without the presence of inhibitors of various efflux transport proteins. In vivo microdialysis simultaneously monitored fluorescein concentrations in cortical extracellular fluid and cerebrospinal fluid. The effect of probenecid on the in vivo distribution of fluorescein was studied using a balanced crossover design in the rat.Results. In vitro experiments showed that probenecid, indomethacin, LY-329146, and all MRP inhibitors significantly increased (two- to threefold) the accumulation of fluorescein in BBMEC, whereas LY-335979, a P-gp inhibitor, had no effect on the accumulation of fluorescein. Probenecid significantly increased fluorescein plasma concentration and the plasma free fraction in vivo. The distribution of fluorescein across the BBB and BCSFB was enhanced by 2.2- and 1.9-fold, respectively, when probenecid was coadministered, even after correction for increased fluorescein plasma concentrations and free fraction. Conclusions. These results demonstrate that MRPs or MRP-like transport system(s) may play an important role in fluorescein distribution across both BBB and BCSFB. This study showed that microdialysis proved to be a powerful in vivo technique for the study of transport systems in the central nervous system, and in vitro/in vivo correlations are possible using these model systems.     

Evidence for Different ABC-Transporters in Caco-2 Cells Modulating Drug Uptake

Purpose. Secretory systems contribute to drug absorption in the gastrointestinal tract. The purpose of this study was the identification of members of the ATP binding cassette superfamily of secretory transport proteins that may potentially modulate drug absorption in Caco-2 cells, which are an important cellular model predicting enteral absorption of drugs. Methods. Kinetic studies as well as PCR- and Western blot studies with confluent epithelial layers of human Caco-2 cells. Results. The study demonstrates functional expression of multidrug resistance related protein (MRP) and P-glycoprotein (P-gp) in Caco-2 cells: 1) Efflux studies with the MRP specific substrate glutathion-methylfluorescein (GS-MF) showed functional activity of MRP in Caco-2 cells preloaded with the metabolic precursor of GS-MF, chloro-methylfluoresceine-diacetate, CMFDA. Excretion of GS-MF was decreased in presence of the MRP-blocker MK-571.2) Transport experiments with cyclosporin A demonstrated the functional activity of P-gp. Cellular accumulation was increased in presence of the P-gp blocking agent SDZ-PSC 833.3) The expression of the 190 kDa protein MRP and the 170 kDa protein P-gp in Caco-2 cells was shown by Western blot analysis with specific monoclonal antibodies. 4) The expression of MRP-mRNA in Caco-2 cells was detected by RT-PCR and compared with the MRP over-expressing cell line H69AR. MRP primers recognize specifically human MRP1 (GenBank accession number L05628), but not all other published sequences of MRP (MRP2-MRP6). P-gp expression on mRNA-level was also confirmed by RT-PCR. Conclusions. The data demonstrate that besides P-gp, multidrug resistance related protein (MRP) is functionally expressed in Caco-2 cells and contributes to the active excretion of substrates in this cell line.     

Synergistic anti-cancer activity of the combination of dihydroartemisinin and doxorubicin in breast cancer cells

BackgroundDihydroartemisinin (DHA) exhibits potent anti-malarial and anti-cancer activities. This study aimed to investigate the anti-proliferative effects of a combination of DHA and doxorubicin (DOX) on human breast cancer cells.MethodsMTT assay and the combination index (CI) were used to show the anti-proliferative effects and calculate the synergism potential, respectively. Flow cytometry assay was used to detect apoptosis and the intracellular accumulation of DOX. JC-1 staining was used to determine the mitochondrial membrane potential. Western blot analysis was used to detect the protein expression of some apoptosis-related molecules.ResultsAsynergistic anti-proliferative effect was found, and the enhanced anti-cancer activity was observed to be accompanied by the prompt onset of apoptosis in MCF-7 cells. The combinative treatment remarkably decreased the mitochondrial membrane potential and activated caspase cascades more than the mono-treatment. Pretreatment with DHAalso did not influence the accumulation of DOX in MCF-7 cells.ConclusionThis study presented a new opportunity to enhance the effectiveness of future treatment regimens of breast cancer using DOX.     

Selection of P-Glycoprotein Inhibitor and Formulation of Combinational Nanoformulation Containing Selected Agent Curcumin and DOX for Reversal of Resistance in K562 Cells

Purpose

To select P-glycoprotein (P-gp) inhibitor from natural source for reversal of DOX resistance in K562 cells and to develop selected one in to nanoformulation in combination with DOX.

Methods

DOX resistant K562 (K562R) cells were developed and reversal of resistance by P-gp inhibitor was validated by co-treatment with verapamil. The p-gp inhibitors were evaluated for their potential to inhibit P-gp (calcein assay) and to reverse drug resistance (XTT cell viability assay). The selected agent, curcumin was formulated in to liposome along with DOX and characterized for size, zeta potential, encapsulation efficiency and release rate. Uptake, P-gp inhibition and reversal of acquired drug resistance in K562R cells were performed.

Results

P-gp inhibitors such as biochanin-A and curcumin were marked suitable for combination with DOX. However, only curcumin could increase the sensitivity of DOX at all dosing levels, therefore used for further studies. Liposomes loaded with curcumin were formulated and characterized where a prolonged release was observed. The uptake of liposomal curcumin was comparable to nanodispersed curcumin but had lower cytotoxicity. DOX and curcumin coloaded liposomes successfully reversed DOX resistance in K562 cells. Conclusion: The coloaded liposomes increased the safety of curcumin with improved efficacy thus can be employed for reversal of acquired DOX resistance.

     

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

BackgroundAnalysis 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. deceased organ donor livers and non-tumorous tissue from metastatic livers, which are also applied for drug transporter investigations. However, no information has yet been published on drug transporters in these two major types of reference livers.MethodsWe explored ABC (P-gp, MRP1, MRP2, MRP3, MRP4, BCRP, BSEP) and SLC (NTCP, MCT1, OCT1, OCT3, OAT2, OATP1B1, OATP1B3, OATP2B1) family transporters expression (qPCR) and protein abundance (LC–MS/MS) in healthy donors (n = 9) and metastatic (n = 13) livers.ResultsThe analysis of mRNA content revealed significant differences in ABCB11, ABCC1, ABCG2, SLC10A1, SLC16A1, SLCO1B1 and SLCO2B1 gene expression between livers from organ donors and patients who underwent surgical resection of metastatic tumors. The protein abundance of NTCP was significantly higher, whereas of P-gp significantly lower in non-tumorous tissues from metastatic livers. Greater inter-individual variability in protein abundance of all studied transporters in subjects with metastatic colon cancer was also observed.ConclusionsThe results suggest that final conclusions in liver pathology studies may depend on the reference liver tissue used, especially in gene expression studies.