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Kienhuis, A.S. (author), Wortelboer, H.M. (author), Hoflack, J.C. (author), Moonen, E.J. (author), Kleinjans, J.C.S. (author), van Ommen, B. (author), van Delft, J.H.M. (author), Stierum, R.H. (author), TNO Kwaliteit van Leven (author)
Sandwich-cultured primary rat hepatocytes are often used as an in vitro model in toxicology and pharmacology. However, loss of liver-specific functions, in particular, the decline of cytochrome P450 (P450) enzyme activity, limits the value of this model for prediction of in vivo toxicity. In this study, we investigated whether a hepatic in vitro...
article 2006
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van Zanden, J.J. (author), Geraets, L. (author), Wortelboer, H.M. (author), van Bladeren, P.J. (author), Rietjens, I.M.C.M. (author), Cnubben, N.H.P. (author), TNO Voeding (author)
The objective of this study was to investigate the structural requirements necessary for inhibition of glutathione S-transferase P1-1 (GSTP1-1) and GS-X pump (MRP1 and MRP2) activity by structurally related flavonoids, in GSTP1-1 transfected MCF7 cells (pMTG5). The results reveal that GSTP1-1 activity in MCF7 pMTG5 cells can be inhibited by some...
article 2004
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Stevens, L.J. (author), van Lipzig, M.M.H. (author), Erpelinck, S.L.A. (author), Pronk, A. (author), van Gorp, J. (author), Wortelboer, H.M. (author), van de Steeg, E. (author)
A majority of the preclinical intestinal screening models do not properly reflect the complex physiology of the human intestinal tract, resulting in low translational value to the clinical situation. The often used cell lines such as Caco-2 or HT-29 are not well suited to investigate the different processes that predict oral bioavailability in...
article 2019
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Cnubben, N.H. (author), Wortelboer, H.M. (author), van Zanden, J.J. (author), Rietjens, I.M. (author), van Bladeren, P.J. (author), TNO Kwaliteit van Leven (author)
Membrane transport proteins belonging to the ATP-binding cassette (ABC) family of transport proteins play a central role in the defence of organisms against toxic compounds, including anticancer drugs. However, for compounds that are designed to display a toxic effect, this defence system diminishes their effectiveness. This is typically the...
article 2005
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Balvers, M.G.J. (author), Verhoeckx, K.C.M. (author), Wortelboer, H.M. (author), Bijlsma, S. (author), Rubingh, C.M. (author), Meijerink, J. (author), Witkamp, R.F. (author)
It is well established that dietary intake of n-3 fatty acids is associated with anti-inflammatory effects, and this has been linked to modulation of the oxylipin and endocannabinoid metabolomes. However, the amount of data on specific tissue effects is limited, and it is not known how inflammation affects this relation. In the present study we...
article 2012
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Usta, M. (author), Wortelboer, H.M. (author), Vervoort, J. (author), Boersma, M.G. (author), Rietjens, I.M.C.M. (author), van Bladeren, P.J. (author), Cnubben, N.H.P. (author), TNO Kwaliteit van Leven (author)
Curcumin, an α,β-unsaturated carbonyl compound, reacts with glutathione, leading to the formation of two monoglutathionyl curcumin conjugates. In the present study, the structures of both glutathione conjugates of curcumin were identified by LC-MS and one- and two-dimensional 1H NMR analysis, and their formation in incubations with human...
article 2007
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Balvers, M.G.J. (author), Wortelboer, H.M. (author), Witkamp, R.F. (author), Verhoeckx, K.C.M. (author)
The origin of N-acyl ethanolamides (NAEs) in plasma is not well understood, and it is possible that NAEs are present in plasma in esterified form. To test this hypothesis, a new and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of arachidonoyl ethanolamide, 2...
article 2013
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Roeselers, G. (author), Ponomarenko, M. (author), Lukovac, S. (author), Wortelboer, H.M. (author)
It is increasingly apparent that the microbial ecosystems in the mammalian gastrointestinal tract play an intricate role in health and disease. There is a growing interest in the development of targeted strategies for modulating health through the modification of these microbiota. Ecologists are faced with the challenge of understanding the...
article 2013
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van de Steeg, E. (author), Greupink, R. (author), Schreurs, M. (author), Nooijen, I.H.G. (author), Verhoeck, K.C.M. (author), Hanemaaijer, R. (author), Ripken, D. (author), Monshouwer, M. (author), Vlaming, M.L.H. (author), DeGroot, J. (author), Verwei, M. (author), Russel, F.G.M. (author), Huisman, M.T. (author), Wortelboer, H.M. (author)
Organic anion-transporting polypeptide 1B1 (OATP1B1) is an important hepatic uptake transporter, of which the polymorphic variant OATP1B1*15 (Asn130Asp and Val174Ala) has been associated with decreased transport activity. Rosuvastatin is an OATP1B1 substrate and often concomitantly prescribed with oral antidiabetics in the clinic. The aim of...
article 2013
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Kubbinga, M. (author), Augustijns, P. (author), Garcia, M.A. (author), Heinen, C. (author), Wortelboer, H.M. (author), Verwei, M. (author), Langguth, P. (author)
Chitosan is object of pharmaceutical research as a candidate permeability enhancer. However, chitosan was recently shown to reduce the oral bioavailability of acyclovir in humans. The effect of chitosan on two processes determining the oral bioavailability of acyclovir, bioaccessibility and intestinal absorption, was now investigated. Acyclovir...
article 2019
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van Zanden, J.J. (author), van der Woude, H. (author), Vaessen, J. (author), Usta, M. (author), Wortelboer, H.M. (author), Cnubben, N.H.P. (author), Rietjens, I.M.C.M. (author), TNO Kwaliteit van Leven (author)
The present study characterises the effect of phase II metabolism, especially methylation and glucuronidation, of the model flavonoid quercetin on its capacity to inhibit human MRP1 and MRP2 activity in Sf9 inside-out vesicles. The results obtained reveal that 3′-O-methylation does not affect the MRP inhibitory potential of quercetin. However, 4...
article 2007
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Vaessen, S.F.C. (author), van Lipzig, M.M.H. (author), Pieters, R.H.H. (author), Krul, C.A.M. (author), Wortelboer, H.M. (author), van de Steeg, E. (author)
Intestinal transporter proteins and metabolizing enzymes play a crucial role in the oral absorption of a wide variety of drugs. The aim of the current study was to characterize better available intestinal in vitro models by comparing expression levels of these proteins and enzymes between porcine intestine, human intestine, and Caco-2 cells. We...
article 2017
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Voortman, T. (author), Hendriks, H.F.J. (author), Witkamp, R.F. (author), Wortelboer, H.M. (author)
Gastrointestinal (GI) peptide hormones play an important role in short-term regulation of food intake and blood glucose levels. Modulating their release is of potential relevance for weight management and possibly diabetes. As currently available models are hard to extrapolate to the human situation, the use of porcine intestinal tissue,...
article 2012
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Bentz, J. (author), O'Connor, M.P. (author), Bednarczyk, D. (author), Coleman, J. (author), Lee, C. (author), Palm, J. (author), Pak, Y.A. (author), Perloff, E.S. (author), Reyner, E. (author), Balimane, P. (author), Brännström, M. (author), Chu, X. (author), Funk, C. (author), Guo, A. (author), Hanna, I. (author), Herédi-Szabó, K. (author), Hillgren, K. (author), Li, L. (author), Hollnack-Pusch, E. (author), Jamei, M. (author), Lin, X. (author), Mason, A.K. (author), Neuhoff, S. (author), Patel, A. (author), Podila, L. (author), Plise, E. (author), Rajaraman, G. (author), Salphati, L. (author), Sands, E. (author), Taub, M.E. (author), Taur, J.-S. (author), Weitz, D. (author), Wortelboer, H.M. (author), Xia, C.Q. (author), Xiao, G. (author), Yabut, J. (author), Yamagata, T. (author), Zhang, L. (author), Ellens, H. (author)
A P-glycoprotein (P-gp) IC50 working group was established with 23 participating pharmaceutical and contract research laboratories and one academic institution to assess interlaboratory variability in P-gp IC 50 determinations. Each laboratory followed its in-house protocol to determine in vitro IC50 values for 16 inhibitors using four different...
article 2013
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Bosgra, S. (author), van de Steeg, E. (author), Vlaming, M.L. (author), Verhoeckx, K.C. (author), Huisman, M.T. (author), Verwei, M. (author), Wortelboer, H.M. (author)
In contrast to primary hepatocytes, estimating carrier-mediated hepatic disposition by using a panel of single transfected cell-lines provides direct information on the contribution of the individual transporters to the net disposition. The most direct way to correct for differences in transporter abundance between cell-lines and tissue is by...
article 2014
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Westerhout, J. (author), van de Steeg, E. (author), Grossouw, D. (author), Zeijdner, E.E. (author), Krul, C.A.M. (author), Verwei, M. (author), Wortelboer, H.M. (author)
A reliable prediction of the oral bioavailability in humans is crucial and of high interest for pharmaceutical and food industry. The predictive value of currently used in silico methods, in vitro cell lines, ex vivo intestinal tissue and/or in vivo animal studies for human intestinal absorption, however, is often insufficient, especially when...
article 2014
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Kienhuis, A.S. (author), van de Poll, M.C.G. (author), Wortelboer, H. (author), van Herwijnen, M. (author), Gottschalk, R. (author), de Jong, C.H.C. (author), Boorsma, A. (author), Paules, R.S. (author), Kleinjans, J.C.S. (author), Stierum, R.H. (author), van Delft, J.H.M. (author), TNO Kwaliteit van Leven (author)
The frequent use of rodent hepatic in vitro systems in pharmacological and toxicological investigations challenges extrapolation of in vitro results to the situation in vivo and interspecies extrapolation from rodents to humans. The toxicogenomics approach may aid in evaluating relevance of these model systems for human risk assessment by direct...
article 2009
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Ripken, D. (author), van der Wielen, N. (author), Wortelboer, H.M. (author), Meijerink, J. (author), Witkamp, R.F. (author), Hendriks, H.F.J. (author)
Glucagon like peptide-1 (GLP-1) and serotonin are both involved in food intake regulation. GLP-1 release is stimulated upon nutrient interaction with G-protein coupled receptors by enteroendocrine cells (EEC), whereas serotonin is released from enterochromaffin cells (ECC). The central hypothesis for the current study was that nutrient-induced...
article 2016
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Balvers, M.G.J. (author), Verhoeckx, K.C.M. (author), Plastina, P. (author), Wortelboer, H.M. (author), Meijerink, J. (author), Witkamp, R.F. (author), TNO Kwaliteit van Leven (author)
n-3 PUFAs have beneficial health effects which are believed to be partly related to their anti-inflammatory properties, however the exact mechanisms behind this are unknown. One possible explanation could be via their conversion to N-acyl ethanolamines (NAEs), which are known to possess anti-inflammatory properties. Using fatty acid precursors...
article 2010
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Joosen, M.J.A. (author), van der Schans, M.J. (author), van Dijk, C.G.M. (author), Kuijpers, W.C. (author), Wortelboer, H.M. (author), van Helden, H.P.M. (author)
One of the shortcomings of current treatment of nerve agent poisoning is that oximes hardly penetrate the blood-brain barrier (BBB), whereas nerve agents easily do. Increasing the concentration of oximes in the brain, would therefore provide an attractive approach to improve medical countermeasures. An explanation for limited penetration might...
article 2011
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