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Grinberg, M. (author), Stöber, R.M. (author), Edlund, K. (author), Rempel, E. (author), Godoy, P. (author), Reif, R. (author), Widera, A. (author), Madjar, K. (author), Schmidt-Heck, W. (author), Marchan, R. (author), Sachinidis, A. (author), Spitkovsky, D. (author), Hescheler, J. (author), Carmo, H. (author), Arbo, M.D. (author), van de Water, B. (author), Wink, S. (author), Vinken, M. (author), Rogiers, V. (author), Escher, S. (author), Hardy, B. (author), Mitic, D. (author), Myatt, G. (author), Waldmann, T. (author), Mardinoglu, A. (author), Damm, G. (author), Seehofer, D. (author), Nüssler, A. (author), Weiss, T.S. (author), Oberemm, A. (author), Lampen, A. (author), Schaap, M.M. (author), Luijten, M. (author), van Steeg, H. (author), Thasler, W.E. (author), Kleinjans, J.C.S. (author), Stierum, R.H. (author), Leist, M. (author), Rahnenführer, J. (author), Hengstler, J.G. (author)Correction to: Arch Toxicol (2014) 88:2261–2287 https://doi.org/10.1007/s00204-014-1400-x.article 2022
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Mesens, N. (author), Crawfordb, A.D. (author), Menke, A. (author), Hung, P.D. (author), van Goethem, F. (author), Nuyts, R. (author), Hansen, E. (author), Wolterbeek, A. (author), van Gompel, J. (author), de Witte, P. (author), Esguerra, C.V. (author)Drug-induced liver injury (DILI) is poorly predicted by single-cell-based assays, probably because of the lack of physiological interactions with other cells within the liver. An intact whole liver system such as one present in zebrafish larvae could provide added value in a screening strategy for DILI; however, the possible occurrence of other...article 2015
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Grinberg, M. (author), Stöber, R.M. (author), Edlund, K. (author), Rempel, E. (author), Godoy, P. (author), Reif, R. (author), Widera, A. (author), Madjar, K. (author), Schmidt-Heck, W. (author), Marchan, R. (author), Sachinidis, A. (author), Spitkovsky, D. (author), Hescheler, J. (author), Carmo, H. (author), Arbo, M.D. (author), van de Water, B. (author), Wink, S. (author), Vinken, M. (author), Rogiers, V. (author), Escher, S. (author), Hardy, B. (author), Mitic, D. (author), Myatt, G. (author), Waldmann, T. (author), Mardinoglu, A. (author), Damm, G. (author), Seehofer, D. (author), Nüssler, A. (author), Weiss, T.S. (author), Oberemm, A. (author), Lampen, A. (author), Schaap, M.M. (author), Luijten, M. (author), van Steeg, H. (author), Thasler, W.E. (author), Kleinjans, J.C.S. (author), Stierum, R.H. (author), Leist, M. (author), Rahnenführer, J. (author), Hengstler, J.G. (author)A long-term goal of numerous research projects is to identify biomarkers for in vitro systems predicting toxicity in vivo. Often, transcriptomics data are used to identify candidates for further evaluation. However, a systematic directory summarizing key features of chemically influenced genes in human hepatocytes is not yet available. To bridge...article 2014
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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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Beker van Woudenberg, A. (author), Snel, C. (author), Rijkmans, E. (author), de Groot, D. (author), Bouma, M. (author), Hermsen, S. (author), Piersma, A. (author), Menke, A. (author), Wolterbeek, A. (author)To improve the predictability of the zebrafish embryotoxicity test (ZET) for developmental (neuro)toxicity screening, we used a multiple-endpoints strategy, including morphology, motor activity (MA), histopathology and kinetics. The model compounds used were antiepileptic drugs (AEDs): valproic acid (VPA), carbamazepine (CBZ), ethosuximide (ETH)...article 2014
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Kleemann, R. (author), Verschuren, L. (author), Morrison, M. (author), Zadelaar, A.S.M. (author), van Erk, M.J. (author), Wielinga, P.Y. (author), Kooistra, T. (author)Objective: Polyphenols such as quercetin may exert several beneficial effects, including those resulting from anti-inflammatory activities, but their impact on cardiovascular health is debated. We investigated the effect of quercetin on cardiovascular risk markers including human C-reactive protein (CRP) and on atherosclerosis using transgenic...article 2011
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Treijtel, N. (author), Eijkeren, J.C.H.v. (author), Nijmeijer, S. (author), van der Greef de - Sandt, I.C.J. (author), Freidig, A.P. (author), TNO Kwaliteit van Leven (author)The metabolism and active transport of ritonavir and saquinavir were studied using sandwich-cultured rat hepatoyctes and rat liver microsomes. For ritonavir four comparable metabolites were observed in the sandwich-culture and in microsomes. For saquinavir eight metabolites were observed in sandwich-culture and 14 different metabolites in...article 2009
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Kienhuis, A.S. (author), van de Poll, M.C.G. (author), de Jong, C.H.C. (author), Gottschalk, R. (author), van Herwijnen, M. (author), Boorsma, A. (author), Kleinjans, J.C.S. (author), Stierum, R.H. (author), van Delft, J.H.M. (author), TNO Kwaliteit van Leven (author)A compound for which marked species differences have been reported in laboratory animals and humans is coumarin. In rats, metabolites of coumarin are highly toxic, whereas in humans, the compound is mainly metabolized to non-toxic metabolites. In the present study, a toxicogenomics-based parallelogram approach was used to compare effects of...article 2009
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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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Parker, A.L. (author), Waddington, S.N. (author), Buckley, S.M.K. (author), Custers, J. (author), Havenga, M.J.E. (author), van Rooijen, N. (author), Goudsmit, J. (author), McVey, J.H. (author), Nicklin, S.A. (author), Baker, A.H. (author), TNO Kwaliteit van Leven (author)The deployment of adenovirus serotype 5 (Ad5)-based vectors is hampered by preexisting immunity. When such vectors are delivered intravenously, hepatocyte transduction is mediated by the hexon-coagulation factor X (FX) interaction. Here, we demonstrate that human sera efficiently block FX-mediated cellular binding and transduction of Ad5-based...article 2009
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Kuhlmann, K.F.D. (author), van Geer, M.A. (author), Bakker, C.T. (author), Dekker, J.E.M. (author), Havenga, M.J.E. (author), Oude Elferink, R.P.J. (author), Gouma, D.J. (author), Bosma, P.J. (author), Wesseling, J.G. (author), TNO Kwaliteit van Leven (author)Survival of patients with pancreatic cancer is poor. Adenoviral (Ad) gene therapy employing the commonly used serotype 5 reveals limited transduction efficiency due to the low amount of coxsackie-adenovirus receptor on pancreatic cancer cells. To identify fiber-chimeric adenoviruses with improved gene transfer, a library of Ad vectors based on...article 2009
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de Haan, W. (author), Out, R. (author), Berbée, J.F.P. (author), van der Hoogt, C.C. (author), Dijk, K.W.v. (author), van Berkel, T.J.C. (author), Romijn, J.A. (author), Wouter Jukema, J. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), TNO Kwaliteit van Leven (author)Apolipoprotein CI (apoCI) has been suggested to influence HDL metabolism by activation of LCAT and inhibition of HL and CETP. However, the effect of apoCI on scavenger receptor BI (SR-BI)-mediated uptake of HDL-cholesteryl esters (CE), as well as the net effect of apoCI on HDL metabolism in vivo is unknown. Therefore, we evaluated the effect of...article 2008
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Price, R.J. (author), Scott, M.P. (author), Giddings, A.M. (author), Walters, D.G. (author), Stierum, R.H. (author), Meredith, C. (author), Lake, B.G. (author), TNO Kwaliteit van Leven (author)1. The objective of this study was to investigate the effects of four food chemicals, namely butylated hydroxytoluene (BHT), curcumin (CC), propyl gallate (PG) and thiabendazole (TB), on cytochrome P450 (CYP) forms in cultured human hepatocytes. 2. Treatment of human hepatocytes for 72 h with 2-200 μM TB produced concentration-dependent...article 2008
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TNO Kwaliteit van Leven (author), Hu, L. (author), van der Hoogt, C.C. (author), Espirito Santo, S.M.S. (author), Out, R. (author), Kypreos, K.E. (author), van Vlijmen, B.J.M. (author), van Berkel, T.J.C. (author), Romijn, J.A. (author), Havekes, L.M. (author), van Dijk, K.W. (author), Rensen, P.C.N. (author)LPL activity plays an important role in preceding the VLDL remnant clearance via the three major apolipoprotein E (apoE)-recognizing receptors: the LDL receptor (LDLr), LDL receptor-related protein (LRP), and VLDL receptor (VLDLr). The aim of this study was to determine whether LPL activity is also important for VLDL remnant clearance...article 2008
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Kienhuis, A.S. (author), Wortelboer, H.M. (author), Maas, W.J. (author), van Herwijnen, M. (author), Kleinjans, J.C.S. (author), van Delft, J.H.M. (author), Stierum, R.H. (author), TNO Kwaliteit van Leven (author)A rapid decline of cytochrome P450 (CYP450) enzyme activities remains a drawback of rat hepatocyte-based in vitro cultures. Consequently, judgment of the toxic potential of compounds that need bioactivation by CYP450s may not be adequate using this model. In the present study, an improved hepatocyte-based in vitro system was developed with...article 2007
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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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Treijtel, N. (author), Barendregt, A. (author), Freidig, A.P. (author), Blaauboer, B.J. (author), van Eijkeren, J.C.H. (author), TNO Voeding (author)An alternative approach is introduced in determining the in vitro intrinsic clearance of slowly metabolized compounds. The long-term sandwich rat hepatocyte culture was exploited, allowing for sufficient substrate depletion to obtain a reliable clearance estimation; in its physiology, it resembles the in vivo liver, thus allowing in vivo...article 2004
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van der Woude, H. (author), Boersma, M.G. (author), Vervoort, J. (author), Rietjens, I.M.C.M. (author), TNO Voeding (author)In this study, the HPLC, UV-vis, LC-MS, and 1H NMR characteristics of 14 different phase II mono- and mixed conjugates of quercetin were determined, providing a useful tool in the identification of quercetin phase II metabolite patterns in various biological systems. Using these data, the phase II metabolism of quercetin by different rat and...article 2004
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Kleemann, R. (author), Verschuren, L. (author), de Rooij, B.J. (author), Lindeman, J. (author), de Maat, M.M. (author), Szalai, A.J. (author), Princen, H.M.G. (author), Kooistra, T. (author), Gaubius Instituut TNO (author)Inflammatory processes, aside from cholesterol, play a central role in atherogenesis. Human C-reactive protein (huCRP) signals systemic inflammation and independently predicts future cardiovascular risk. Cholesterol-lowering statins reduce atherosclerosis and plasma huCRP levels. Evidence is sought for a direct anti-inflammatory statin effect in...article 2004
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TNO Preventie en Gezondheid (author), Out, R. (author), Kruijt, J.K. (author), Rensen, P.C.N. (author), Hildebrand, R.B. (author), de Vos, P. (author), van Eck, M. (author), van Berkel, T.J.C. (author)The function of scavenger receptor class B type I (SR-BI) in mediating the selective uptake of high density lipoprotein (HDL) cholesterol esters is well established. However, the potential role of SR-BI in chylomicron and chylomicron remnant metabolism is largely unknown. In the present investigation, we report that the cell association of 160...article 2004