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Bakker, G.C.M. (author), van Erk, M.J. (author), Pellis, L. (author), Wopereis, S. (author), Rubingh, C.M. (author), Cnubben, N.H.P. (author), Kooistra, T. (author), van Ommen, B. (author), Hendriks, H.F.J. (author), TNO Kwaliteit van Leven (author)
Background: Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. Objective: It was hypothesized that specific dietary components are able to reduce low-grade inflammation as well as metabolic and oxidative stress. Design: Dietary products [resveratrol, green tea extract, α-tocopherol,...
article 2010
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TNO Kwaliteit van Leven (author), Wopereis, S. (author), de Rubingh, C.M. (author), van Erk, M.J. (author), Verheij, E.R. (author), van Vliet, T. (author), Cnubben, N.H. (author), Smilde, A.K. (author), van der Greef, J. (author), van Ommen, B. (author), Hendriks, H.F. (author)
BACKGROUND: The prevalence of overweight is increasing globally and has become a serious health problem. Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. Novel tools to understand these processes are needed. Metabolic profiling is one such tool that can provide novel insights into...
article 2009
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Jeurissen, S.M.F. (author), Claassen, F.W. (author), Havlik, J. (author), Bouwmans, E.E. (author), Cnubben, N.H.P. (author), Sudhölter, E.J.R. (author), Rietjens, I.M.C.M. (author), van Beek, T.A. (author), TNO Kwaliteit van Leven (author)
An on-line HPLC screening method for detection of inhibitors of human cytochrome P450 1A2 in extracts was developed. HPLC separation of extracts is connected to a continuous methoxyresorufin-O-demethylation (MROD) assay in which recombinant human P450 1A2 converts methoxyresorufin to its fluorescent metabolite resorufin. The system was tested...
article 2007
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Jeurissen, S.M.F. (author), Punt, A. (author), Boersma, M.G. (author), Bogaards, J.J.P. (author), Fiamegos, Y.C. (author), Schilter, B. (author), van Bladeren, P.J. (author), Cnubben, N.H.P. (author), Rietjens, I.M.C.M. (author), TNO Kwaliteit van Leven (author)
Human cytochrome P450 enzymes involved in the bioactivation of estragole to its proximate carcinogen 1′-hydroxyestragole were identified and compared to the enzymes of importance for 1′-hydroxylation of the related alkenylbenzenes methyleugenol and safrole. Incubations with Supersomes revealed that all enzymes tested, except P450 2C8, are...
article 2007
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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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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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Jeurissen, S.M.F. (author), Bogaards, J.J.P. (author), Boersma, M.G. (author), ter Horst, J.P.F. (author), Awad, H.M. (author), Fiamegos, Y.C. (author), van Beek, T.A. (author), Alink, G.M. (author), Sudhölter, E.J.R. (author), Cnubben, N.H.P. (author), Rietjens, I.M.C.M. (author), TNO Kwaliteit van Leven (author)
In vitro studies were performed to elucidate the human cytochrome P450 enzymes involved in the bioactivation of methyleugenol to its proximate carcinogen 1′-hydroxymethyleugenol. Incubations with Supersomes, expressing individual P450 enzymes to a high level, revealed that P450 1A2, 2A6, 2C9, 2C19, and 2D6 are intrinsically able to 1′...
article 2006
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Brand, W. (author), Schutte, M.E. (author), Williamson, G. (author), van Zanden, J.J. (author), Cnubben, N.H.P. (author), Groten, J.P. (author), van Bladeren, P.J. (author), Rietjens, I.M.C.M. (author), TNO Kwaliteit van Leven (author)
The transcellular transport of ingested food ingredients across the intestinal epithelial barrier is an important factor determining bioavailability upon oral intake. This transcellular transport of many chemicals, food ingredients, drugs or toxic compounds over the intestinal epithelium can be highly dependent on the activity of membrane bound...
article 2006
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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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van Zanden, J.J. (author), de Mul, A. (author), Wortelboer, H.M. (author), Usta, M. (author), van Bladeren, P.J. (author), Rietjens, I.M.C.M. (author), Cnubben, N.H.P. (author), TNO Kwaliteit van Leven (author)
In the present study, the effects of myricetin on either MRP1 or MRP2 mediated vincristine resistance in transfected MDCKII cells were examined. The results obtained show that myricetin can inhibit both MRP1 and MRP2 mediated vincristine efflux in a concentration dependent manner. The IC50 values for cellular vincristine transport inhibition by...
article 2005
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Wortelboer, H.M. (author), Usta, M. (author), van Zanden, J.J. (author), van Bladeren, P.J. (author), Rietjens, I.M.C.M. (author), Cnubben, N.H.P. (author), TNO Kwaliteit van Leven (author)
To study the possible interplay between glutathione metabolism of and MRP inhibition by thiol reactive compounds, the interactions of a series of α,β-unsaturated carbonyl compounds with multidrug resistance proteins 1 and 2 (MRP1/ABCC1 and MRP2/ABCC2) were studied. α,β-Unsaturated carbonyl compounds react with glutathione, and therefore either...
article 2005
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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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Jeurissen, S.M.F. (author), Bogaards, J.J.P. (author), Awad, H.M. (author), Boersma, M.G. (author), Brand, W. (author), Fiamegos, Y.C. (author), van Beek, T.A. (author), Alink, G.M. (author), Sudhölter, E.J.R. (author), Cnubben, N.H.P. (author), Rietjens, I.M.C.M. (author), TNO Voeding (author)
In the present study, the cytochrome P450 mediated bioactivation of safrole to its proximate carcinogenic metabolite, 1′-hydroxysafrole, has been investigated for the purpose of identifying the human P450 enzymes involved. The 1′-hydroxylation of safrole was characterized in a variety of in vitro test systems, including Supersomes, expressing...
article 2004
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van Zanden, J.J. (author), Hamman, O.B. (author), van Iersel, M.L.P.S. (author), Boeren, S. (author), Cnubben, N.H.P. (author), Lo Bello, M. (author), Vervoort, J. (author), van Bladeren, P.J. (author), Rietjens, I.M.C.M. (author)
In the present study, the inhibition of human glutathione S-transferase P1-1 (GSTP1-1) by the flavonoid quercetin has been investigated. The results show a time- and concentration-dependent inhibition of GSTP1-1 by quercetin. GSTP1-1 activity is completely inhibited upon 1 h incubation with 100 μM quercetin or 2 h incubation with 25 μM quercetin...
article 2003
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Wortelboer, H.M. (author), Usta, M. (author), van der Velde, A.E. (author), Boersma, M.G. (author), Spenkelink, B. (author), van Zanden, J.J. (author), Rietjens, I.M.C.M. (author), van Bladeren, P.J. (author), Cnubben, N.H.P. (author)
The multidrug resistance proteins MRP1 and MRP2 are efflux transporters with broad substrate specificity, including glutathione, glucuronide, and sulfate conjugates. In the present study, the interaction of the dietary polyphenol curcumin with MRP1 and MRP2 and the interplay between curcumin-dependent MRP inhibition and its glutathione-dependent...
article 2003
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Cnubben, N.H.P. (author), Elliott, G.R. (author), Hakkert, B.C. (author), Meuling, W.J.A. (author), van de Sandt, J.J.M. (author), TNO Voeding Centraal Instituut voor Voedingsonderzoek TNO (author)
The validity of in vitro and in vivo methods for the prediction of percutaneous penetration in humans was assessed using the fungicide ortho-phenylphenol (OPP) (log Po/w 3.28, MW 170.8, solubility in water 0.7 g/L). In vivo studies were performed in rats and human volunteers, applying the test compound to the dorsal skin and the volar aspect of...
article 2002
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van den Berg, R. (author), van Vliet, T. (author), Broekmans, W.M.R. (author), Cnubben, N.H.P. (author), Vaes, W.H.J. (author), Roza, L. (author), Haenen, G.R.M.M. (author), Bast, A. (author), van den Berg, H. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)
The potential benefits of a high fruit and vegetable intake on the antioxidant status and on relevant biomarkers of oxidative damage to lipids, proteins and DNA and on (functional) markers of oxidative stress were evaluated. A randomized, free living, open placebo-controlled cross-over trial of 3 wk, with a 2-wk washout period between treatments...
article 2001
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van de Sandt, J.J.M. (author), Meuling, W.J.A. (author), Elliott, G.R. (author), Cnubben, N.H.P. (author), Hakkert, B.C. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)
In vitro and in vivo skin absorption of the pesticide propoxur (2-isopropoxyphenyl N-methyl carbamate, commercially Baygon(TM) and Unden(TM); log Po/w 1.56, MW 209.2) was investigated. In vivo studies were performed in rats and human volunteers, applying the test compound to the dorsal skin and the volar aspect of the forearm, respectively. In...
article 2000
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van Iersel, M.L.P.S. (author), Cnubben, N.H.P. (author), Smink, N. (author), Koeman, J.H. (author), van Bladeren, P.J. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)
The cyclopentenone prostaglandin A2 (PGA2) is known to inhibit cell proliferation, and metabolism of this compound thus might be important in controlling its ultimate function. The glutathione-related metabolism of PGA2 was therefore investigated both with purified glutathione S-transferase P1-1 (GSTP1-1) and with IGR-39 human melanoma cells....
article 1999
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Centraal Instituut voor Voedingsonderzoek TNO TNO Voeding (author), Evers, R. (author), Cnubben, N.H.P. (author), Wijnholds, J. (author), van Deemter, L. (author), van Bladeren, P.J. (author), Borst, P. (author)
The human multidrug resistance protein MRP1 mediates transport of organic substrates conjugated to glutathione, glucuronide, or sulfate. The naturally occurring prostaglandins A1 and A2 can form two diastereomeric glutathione S-conjugates, and it has been speculated that these might be substrates for MRP1. Here we present evidence that polarized...
article 1997
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