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Fragki, S.S. (author), Dirven, H. (author), Fletcher, T. (author), Grasl-Kraupp, B. (author), Guetzkow, K.B. (author), Hoogenboom, R. (author), Kersten, S. (author), Lindeman, B. (author), Louisse, J. (author), Peijnenburg, A. (author), Aldert H., (author), Piersma, A.H. (author), Princen, H.M.G. (author), Uhl, M. (author), Westerhout, J. (author), Zeilmaker, M.J. (author), Luijten, M. (author)Associations between per- and polyfluoroalkyl substances (PFASs) and increased blood lipids have been repeatedly observed in humans, but a causal relation has been debated. Rodent studies show reverse effects, i.e. decreased blood cholesterol and triglycerides, occurring however at PFAS serum levels at least 100-fold higher than those in humans....article 2021
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Holmgren, G. (author), Ulfenborg, B. (author), Asplund, A. (author), Toet, K. (author), Andersson, C.X. (author), Hammarstedt, A. (author), Hanemaaijer, J.R.O. (author), Küppers-Munther, B. (author), Synnergren, J. (author)There is a strong anticipated future for human induced pluripotent stem cell-derived hepatocytes (hiPS-HEP), but so far, their use has been limited due to insufficient functionality. We investigated the potential of hiPS-HEP as an in vitro model for metabolic diseases by combining transcriptomics with multiple functional assays. The...article 2020
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Aranda, A. (author), Sequedo, L. (author), Tolosa, L. (author), Quintas, G. (author), Burello, E. (author), Castell, J.V. (author), Gombau, L. (author)No consensus exists on how to address possible toxicity of nanomaterials as they interfere with most in vitro screening tests based on colorimetric and fluorimetric probes such as the dichloro-dihydrofluorescein diacetate (DCFH-DA) assay for detection of oxidative species. In the present research, nanomaterial interaction with DCFH-DA was...article 2013
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Wong, M.C. (author), van Diepen, J.A. (author), Hu, L. (author), Guigas, B. (author), de Boer, H.C. (author), van Puijvelde, G.H. (author), Kuiper, J. (author), van Zonneveld, A.J. (author), Shoelson, S.E. (author), Voshol, P.J. (author), Romijn, J.A. (author), Havekes, L.M. (author), Tamsma, J.T. (author), Rensen, P.C.N. (author), Hiemstra, P.S. (author), Berbée, J.F.P. (author)Objective: The liver is the key organ involved in systemic inflammation, but the relation between hepatic inflammation and atherogenesis is poorly understood. Since nuclear factor-κB (NF-κB) is a central regulator of inflammatory processes, we hypothesized that chronically enhanced hepatic NF-κB activation, through hepatocyte-specific expression...article 2012
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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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TNO Kwaliteit van Leven (author), Mathijs, K. (author), Brauers, K.J.J. (author), Jennen, D.G.J. (author), Boorsma, A. (author), van Herwijnen, M.H.M. (author), Gottschalk, R.W.H. (author), Kleinjans, J.C.S. (author), van Delft, J.H.M. (author)Assessing the potential carcinogenicity of chemicals for humans represents an ongoing challenge. Chronic rodent bioassays predict human cancer risk at only limited reliability and are simultaneously expensive and long lasting. In order to seek for alternatives, the ability of a transcriptomics-based primary mouse hepatocyte model to classify...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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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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Heijboer, A.C. (author), van den Hoek, A.M. (author), Parlevliet, E.T. (author), Havekes, L.M. (author), Romijn, J.A. (author), Pijl, H. (author), Corssmit, E.P.M. (author), TNO Kwaliteit van Leven (author)Aims/hypothesis: This study was conducted to evaluate the effects of ghrelin on insulin's capacity to suppress endogenous glucose production and promote glucose disposal in mice. To establish whether the growth hormone secretagogue (GHS) receptor can mediate the putative effect of ghrelin on the action of insulin, we also determined the...article 2006
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Berbée, J.F.P. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), TNO Kwaliteit van Leven (author)An increasing body of evidence demonstrates a close interplay between lipoprotein metabolism and sepsis. Sepsis results in an increase of plasma triglycerides within VLDL as a consequence of an enhanced hepatic VLDL production and/or inhibited peripheral and hepatic VLDL clearance. In contrast, sepsis decreases plasma cholesterol within LDL and...article 2005
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TNO Kwaliteit van Leven (author), Verschuur, M. (author), Jong, M.de (author), Felida, L. (author), Maat, M.P.M.de (author), Vos, H.L. (author)An elevated plasma fibrinogen level is an independent risk factor for cardiovascular disease. Therefore, an understanding of the regulation of fibrinogen expression is important. Inflammation and genetic variation of the fibrinogen beta gene regulate plasma fibrinogen levels, and there are indications that inflammation and genetic variation...article 2005
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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