The Experts below are selected from a list of 588 Experts worldwide ranked by ideXlab platform

Veronika Butterweck - One of the best experts on this subject based on the ideXlab platform.

  • Effect of grapefruit juice, naringin, naringenin, and Bergamottin on the intestinal carrier-mediated transport of talinolol in rats.
    Journal of agricultural and food chemistry, 2008
    Co-Authors: Whocely Victor De Castro, Susanne U. Mertens-talcott, Hartmut Derendorf, Veronika Butterweck
    Abstract:

    The effect of two varieties of grapefruit juice (white and ruby red) and its selected components (naringin, naringenin, and Bergamottin) was investigated on the activity of the P-glycoprotein (P-gp) in male Sprague−Dawley rats. Talinolol, a nonmetabolized P-gp substrate, was used as a marker compound. The white grapefruit juice (GFJ) had a minor effect on talinolol pharmacokinetics, but the ruby red GFJ reduced the Cmax and the AUC(0−∞) by 60% and 50% of the control, respectively. However, among the GFJ constituents tested, Bergamottin (0.22 mg/kg) was the most potent component augmenting the Cmax and the AUC(0−∞) of talinolol by 2.4- and 1.8-fold, respectively, if compared to the control group. The flavonoids naringenin (0.7 mg/kg) and naringin (2.4 and 9.4 mg/kg) had a similar effect increasing the talinolol Cmax and AUC(0−∞) by 1.5- to 1.8-fold, respectively. In conclusion, the effect of GFJ on P-gp activity seems to depend on the variety, the concentration of compounds in the juice, and the compositio...

  • Effect of grapefruit juice, naringin, naringenin, and Bergamottin on the intestinal carrier-mediated transport of talinolol in rats.
    Journal of agricultural and food chemistry, 2008
    Co-Authors: Whocely Victor De Castro, Susanne U. Mertens-talcott, Hartmut Derendorf, Veronika Butterweck
    Abstract:

    The effect of two varieties of grapefruit juice (white and ruby red) and its selected components (naringin, naringenin, and Bergamottin) was investigated on the activity of the P-glycoprotein (P-gp) in male Sprague-Dawley rats. Talinolol, a nonmetabolized P-gp substrate, was used as a marker compound. The white grapefruit juice (GFJ) had a minor effect on talinolol pharmacokinetics, but the ruby red GFJ reduced the C max and the AUC (0-infinity) by 60% and 50% of the control, respectively. However, among the GFJ constituents tested, Bergamottin (0.22 mg/kg) was the most potent component augmenting the C max and the AUC (0-infinity) of talinolol by 2.4- and 1.8-fold, respectively, if compared to the control group. The flavonoids naringenin (0.7 mg/kg) and naringin (2.4 and 9.4 mg/kg) had a similar effect increasing the talinolol C max and AUC (0-infinity) by 1.5- to 1.8-fold, respectively. In conclusion, the effect of GFJ on P-gp activity seems to depend on the variety, the concentration of compounds in the juice, and the composition of different ingredients.

  • grapefruit juice drug interactions grapefruit juice and its components inhibit p glycoprotein abcb1 mediated transport of talinolol in caco 2 cells
    Journal of Pharmaceutical Sciences, 2007
    Co-Authors: Whocely Victor De Castro, Hartmut Derendorf, Susanne U Mertenstalcott, Veronika Butterweck
    Abstract:

    To investigate the potential interaction between selected ingredients of grapefruit juice and, the transport of talinolol, a P-gp substrate, across Caco-2 cells monolayers was determined in the absence and presence of distinct concentrations of grapefruit juice, Bergamottin, 6',7'-dihydroxyBergamottin, 6',7'-epoxyBergamottin, naringin, and naringenin. Talinolol permeability was selectively inhibited by grapefruit juice and its components. The furano coumarin, 6',7'-epoxyBergamottin, was the most potent inhibitor (IC(50) = 0.7 microM), followed by 6',7'-dihydroxyBergamottin (IC(50) = 34 microM) and Bergamottin that did not show any inhibition at concentrations up to 10 microM. The flavonoid aglycone naringenin was around 10-fold more potent than its glycoside naringin with IC(50) values of 236 and 2409 microM, respectively. The flavonoids and furanocoumarins tested in this study are in the same range of concentration they are present in the juice contributing, therefore, for the overall inhibitory effect of GFJ on P-gp activity. The in vitro data suggest that compounds present in grapefruit juice are able to inhibit the P-gp activity modifying the disposition of drugs that are P-gp substrates such as talinolol.

  • Grapefruit juice-drug interactions: Grapefruit juice and its components inhibit P-glycoprotein (ABCB1) mediated transport of talinolol in Caco-2 cells.
    Journal of pharmaceutical sciences, 2007
    Co-Authors: Whocely Victor De Castro, Susanne U. Mertens-talcott, Hartmut Derendorf, Veronika Butterweck
    Abstract:

    ABSTRACT To investigate the potential interaction between selected ingredients of grapefruit juice and, the transport of talinolol, a P‐gp substrate, across Caco‐2 cells monolayers was determined in the absence and presence of distinct concentrations of grapefruit juice, Bergamottin, 6′,7′‐dihydroxyBergamottin, 6′,7′‐epoxyBergamottin, naringin, and naringenin. Talinolol permeability was selectively inhibited by grapefruit juice and its components. The furano coumarin, 6′,7′‐epoxyBergamottin, was the most potent inhibitor (IC 50 = 0.7 µM), followed by 6′,7′‐dihydroxyBergamottin (IC 50 = 34 µM) and Bergamottin that did not show any inhibition at concentrations up to 10 µM. The flavonoid aglycone naringenin was around 10‐fold more potent than its glycoside naringin with IC 50 values of 236 and 2409 µM, respectively. The flavonoids and furanocoumarins tested in this study are in the same range of concentration they are present in the juice contributing, therefore, for the overall inhibitory effect of GFJ on P‐gp activity. The in vitro data suggest that compounds present in grapefruit juice are able to inhibit the P‐gp activity modifying the disposition of drugs that are P‐gp substrates such as talinolol. © 2007 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 2808–2817, 2007

  • variation of flavonoids and furanocoumarins in grapefruit juices a potential source of variability in grapefruit juice drug interaction studies
    Journal of Agricultural and Food Chemistry, 2006
    Co-Authors: Whocely Victor De Castro, Veronika Butterweck, Susanne U Mertenstalcott, Anke Rubner, Hartmut Derendorf
    Abstract:

    Grapefruit juice (GFJ) has been found to interact with several medications, increasing their oral bioavailability and the risk of toxicity. Inhibition of CYP3A4 in the small intestine by flavonoids (such as naringin and naringenin) and furanocoumarins (including Bergamottin and 6‘,7‘-dihydroxyBergamottin) present in GFJ seems to be the predominant mechanism, although P-glycoprotein and influx transporters in the small intestine are also involved. The quantity of interactive compounds ingested may affect the magnitude and mechanism of the food−drug interaction. Therefore, these four compounds were quantified by HPLC analysis in commercially available and fresh-squeezed GFJ and in grapefruit tissues. Considerable variability in naringin (174−1492 μmol/L), Bergamottin (1.0−36.6 μmol/L), and 6‘,7‘-dihydroxyBergamottin (0.22−52.5 μmol/L) was observed, whereas naringenin could not be detected. White grapefruit showed higher concentrations of naringin and furanocoumarins located in the albedo and flavedo compare...

John Digiovanni - One of the best experts on this subject based on the ideXlab platform.

  • Naturally occurring coumarins inhibit human cytochromes P450 and block benzo[a]pyrene and 7,12-dimethylbenz[a]anthracene DNA adduct formation in MCF-7 cells.
    Chemical research in toxicology, 2003
    Co-Authors: Heather E Kleiner, Melissa J Reed, John Digiovanni
    Abstract:

    Naturally occurring coumarins (NOCs) inhibit polycyclic aromatic hydrocarbon-induced skin tumor initiation in mice by blocking cytochrome P450 (P450)-mediated bioactivation of benzo[a]pyrene (B[a]P) and 7,12-dimethylbenz[a]anthracene (DMBA). Bergamottin selectively inhibits tumor initiation by B[a]P, whereas imperatorin and isopimpinellin inhibit tumor initiation with both carcinogens. The goals of the current study were to examine the ability of NOCs to inhibit human P450s in vitro and to establish whether NOCs, which are anticarcinogenic in mice, can block carcinogen bioactivation in cultured human cells. For the initial experiments, incubations containing 5 microM P450, P450 substrate, an NADPH generating system, and NOCs were used to determine the concentrations of each inhibitor that blocked 50% of P450 activity (IC(50)). These results confirmed that NOCs are capable of inhibiting multiple human P450s and that they exhibit selectivity for certain isoforms of human P450s. In subsequent experiments, we examined the effects of Bergamottin, imperatorin, and isopimpinellin on DMBA and B[a]P DNA adduct formation in the human breast MCF-7 adenocarcinoma cell line. Coincubation of cells with the three different NOCs significantly inhibited DMBA DNA adduct formation by 29-82% at doses ranging from 2 to 10 microM and significantly inhibited B[a]P DNA adduct formation by 37-80% at doses ranging from 20 to 80 microM. HPLC analysis of the DNA hydrolysates demonstrated that inhibition of DNA adducts corresponded to inhibition of the major B[a]P and DMBA diol-epoxide-derived adducts. Although Bergamottin was not effective at blocking DMBA bioactivation in the mouse skin model, it was similar in effectiveness to imperatorin and isopimpinellin in MCF-7 cells. These results demonstrate that NOCs, which are present in citrus fruits and other components of the human diet, are capable of inhibiting carcinogen metabolizing enzymes and blocking bioactivation of both B[a]P and DMBA in MCF-7 cells.

  • role of cytochrome p450 1a1 and 1b1 in the metabolic activation of 7 12 dimethylbenz a anthracene and the effects of naturally occurring furanocoumarins on skin tumor initiation
    Chemical Research in Toxicology, 2002
    Co-Authors: Heather E Kleiner, Suryanarayana V Vulimiri, Melissa J Reed, And Ann Uberecken, John Digiovanni
    Abstract:

    The current study was designed to determine the mechanistic basis for differences in the effects of naturally occurring furanocoumarins on skin tumor initiation by 7,12-dimethylbenz[a]anthracene (DMBA). Female SENCAR mice were pretreated topically with Bergamottin, imperatorin, or isopimpinellin (100−3200 nmol), 7,8-benzoflavone (7,8-BF, 5−40 nmol, a known inhibitor of DMBA skin carcinogenesis in mice), or acetone (vehicle control) 5 min prior to topical treatment with DMBA (10 nmol). Imperatorin, isopimpinellin, and 7,8-BF, but not Bergamottin, significantly blocked total DMBA-DNA adduct formation. HPLC analysis of DNA adducts revealed that Bergamottin preferentially inhibited formation of anti-DMBA diol-epoxide (DMBADE) derived DNA adducts, imperatorin, and isopimpinellin inhibited both anti- and syn- derived adducts, whereas 7,8-BF showed some selectivity for reduction of syn-DMBADE-DNA adducts. Mouse embryo fibroblast C3H/10T1/2 (10T1/2) cells, and mouse hepatoma-derived 1c1c7 (Hepa-1) cells, which pr...

  • Role of cytochrome P450 1a1 and 1b1 in the metabolic activation of 7,12-dimethylbenz[a]anthracene and the effects of naturally occurring furanocoumarins on skin tumor initiation.
    Chemical research in toxicology, 2002
    Co-Authors: Heather E Kleiner, Suryanarayana V Vulimiri, Melissa J Reed, And Ann Uberecken, John Digiovanni
    Abstract:

    The current study was designed to determine the mechanistic basis for differences in the effects of naturally occurring furanocoumarins on skin tumor initiation by 7,12-dimethylbenz[a]anthracene (DMBA). Female SENCAR mice were pretreated topically with Bergamottin, imperatorin, or isopimpinellin (100-3200 nmol), 7,8-benzoflavone (7,8-BF, 5-40 nmol, a known inhibitor of DMBA skin carcinogenesis in mice), or acetone (vehicle control) 5 min prior to topical treatment with DMBA (10 nmol). Imperatorin, isopimpinellin, and 7,8-BF, but not Bergamottin, significantly blocked total DMBA-DNA adduct formation. HPLC analysis of DNA adducts revealed that Bergamottin preferentially inhibited formation of anti-DMBA diol-epoxide (DMBADE) derived DNA adducts, imperatorin, and isopimpinellin inhibited both anti- and syn- derived adducts, whereas 7,8-BF showed some selectivity for reduction of syn-DMBADE-DNA adducts. Mouse embryo fibroblast C3H/10T1/2 (10T1/2) cells, and mouse hepatoma-derived 1c1c7 (Hepa-1) cells, which preferentially express P450 1b1 and P450 1a1, respectively, were co-incubated with 2 microM Bergamottin, imperatorin, isopimpinellin, and 7,8-BF, and with DMBA (2 microM). Hepa-1 cells (P450 1a1) formed mainly anti-DMBADE-DNA adducts. In contrast, 10T1/2 cells (P450 1b1) formed mainly syn-DMBADE-DNA adducts. Bergamottin inhibited DMBA metabolism to DMBA-3,4-diol and blocked DNA adduct formation in Hepa-1 cells, but had little effect in 10T1/2 cells. In contrast, 7,8-BF completely blocked DMBA metabolism and DNA adduct formation in 10T1/2 cells, but had little effect in Hepa-1 cells. Imperatorin and isopimpinellin inhibited DMBA bioactivation in both cell lines. These results indicate that Bergamottin is a more selective inhibitor of P450 1a1 and overall a less effective inhibitor of the metabolic activation of DMBA in mouse epidermis. In contrast, imperatorin, isopimpinellin, and especially 7,8-BF, which block metabolic activation of DMBA in mouse epidermis, appear more selective for P450 1b1. On the basis of our studies using 10T1/2 cells and Hepa-1 cells, it appears that P450 1a1 is primarily responsible for converting DMBA-3,4-diol to anti-DMBADE, whereas P450 1b1 is primarily responsible for converting DMBA-3,4-diol to syn-DMBADE. These data demonstrate the role of P450 1a1 and 1b1 in the metabolic activation of DMBA in mouse epidermis and provide a mechanistic explanation for the differential effects of naturally occurring furanocoumarins (and 7,8-BF) on polycyclic aromatic hydrocarbon skin carcinogenesis.

  • Effect of naturally occurring coumarins on the formation of epidermal DNA adducts and skin tumors induced by benzo[a]pyrene and 7,12-dimethylbenz[a]anthracene in SENCAR mice.
    Carcinogenesis, 1997
    Co-Authors: Yingna Cai, Heather E Kleiner, Dennis A. Johnston, Adam Dubowski, Samantha Bostic, Wayne Ivie, John Digiovanni
    Abstract:

    Several naturally occurring coumarins previously found to be potent inhibitors of mouse hepatic ethoxyresorufin-O-deethylase (EROD) and/or pentoxyresorufin-O-dealkylase (PROD) were examined for their effects on formation of benzo[a]pyrene (B[a]P) and 7,12-dimethylbenz[a]anthracene (DMBA) DNA adducts in mouse epidermis, as well as, their effects on skin tumor initiation by these polycyclic aromatic hydrocarbons (PAH). Bergamottin, a potent inhibitor of hepatic EROD, given topically 5 min prior to an initiating dose of B[a]P, significantly decreased total covalent binding of B[a]P to DNA in a dose-dependent manner 24 h after treatment. A dose of 400 nmol Bergamottin reduced covalent binding of B[a]P by 72%. Coriandrin, at a dose of 400 nmol also significantly reduced total covalent binding of B[a]P by 59%. In addition, formation of the major (+)anti-B[a]P-diol epoxide-N2-dGuo adduct was selectively reduced by both of these coumarins. In contrast, Bergamottin and coriandrin did not significantly decrease covalent binding of DMBA to epidermal DNA at doses of either 400 nmol or 800 nmol. Imperatorin and isopimpinellin, which are more potent inhibitors of hepatic PROD activity, significantly reduced overall binding of DMBA to epidermal DNA by 67% and 52%, respectively, when applied at doses of 400 nmol. These two coumarins also inhibited B[a]P-DNA adduct formation at similar doses but to a lesser extent. Imperatorin at a dose of 400 nmol dramatically decreased formation of covalent DNA adducts derived from both the anti and syn diol epoxides of DMBA. Bergamottin was a potent inhibitor of tumor initiation by B[a]P while coriandrin was less effective in this regard. Imperatorin was an effective inhibitor of skin tumor initiation by DMBA and also inhibited complete carcinogenesis by this PAH. At dose levels higher than those effective against DMBA, imperatorin also inhibited tumor initiation by B[a]P. The results demonstrate that several naturally occurring coumarins possess the ability to block DNA adduct formation and tumor initiation by PAHs such as B[a]P and DMBA. The mechanism for reduced DNA adduct formation and tumor initiation appears to involve inhibition of the P450s involved in the metabolic activation of these hydrocarbons. Finally, the differential effects of certain coumarins on B[a]P vs DMBA DNA adduct formation and tumor initiation may be useful for dissecting the role of specific cytochromes P450 in their metabolic activation.

  • Inhibitory effects of naturally occurring coumarins on the metabolic activation of benzo[a]pyrene and 7,12-dimethylbenz[a]anthracene in cultured mouse keratinocytes.
    Carcinogenesis, 1997
    Co-Authors: Yingna Cai, Wanda Baer-dubowska, Mike J. Ashwood-smith, John Digiovanni
    Abstract:

    Several naturally occurring coumarins to which humans are routinely exposed have been previously found to be potent inhibitors and inactivators of cytochrome P450 (P450) 1A1-mediated monooxygenase in both murine hepatic microsomes and in a reconstituted system using purified human P450 1A1 [Cai et al. (1993) Chem. Res. Toxicol., 6, 872-879 and Cai et al. (1996) Chem. Res. Toxicol., 9, 729-736]. In the present study, several of these coumarins were investigated for their inhibitory effects on the metabolism and metabolic activation of benzo[a]pyrene (B[a]P) and 7,12-dimethylbenz[a]anthracene (DMBA) in cultured mouse keratinocytes. Initial analysis of B[a]P metabolism in cultured keratinocytes showed that imperatorin, isoimperatorin, coriandrin, and Bergamottin, at concentrations of 2 nM equal with B[a]P, reduced the formation of water-soluble metabolites of B[a]P by 33% to 57%. Bergamottin and coriandrin were the most potent inhibitors of the compounds examined. HPLC analysis of organic solvent-soluble metabolites of B[a]P indicated that all the coumarins tested significantly reduced the formation of individual B[a]P metabolites (including phenols, diols and tetraols). However, the greatest effect was on the formation of B[a]P tetraols. Additional experiments determined the ability of selected coumarins to block covalent binding of B[a]P and DMBA to DNA in keratinocytes. Bergamottin preferentially inhibited the binding of B[a]P to DNA by 56%, while coriandrin preferentially inhibited the binding of DMBA to DNA by 48%. Notably, analysis of individual DNA adducts formed from B[a]P and DMBA indicated that both Bergamottin and coriandrin specifically inhibited the formation of anti diol-epoxide DNA adducts derived from both hydrocarbons. The preferential inhibitory effect of Bergamottin and coriandrin on the formation of anti diol-epoxide adducts derived from DMBA was further confirmed by separation of anti- and syn-diol-epoxide-DNA adducts using immobilized boronate chromatography. The current study demonstrates that certain naturally occurring coumarins inhibited metabolic activation of B[a]P and DMBA in cultured mouse keratinocytes and specifically inhibited the formation of DNA adducts derived from the anti diol-epoxide diastereomers from either hydrocarbon. The current data also suggest that certain naturally occurring coumarins may possess anticarcinogenic activity toward polycyclic aromatic hydrocarbons.

Whocely Victor De Castro - One of the best experts on this subject based on the ideXlab platform.

  • Effect of grapefruit juice, naringin, naringenin, and Bergamottin on the intestinal carrier-mediated transport of talinolol in rats.
    Journal of agricultural and food chemistry, 2008
    Co-Authors: Whocely Victor De Castro, Susanne U. Mertens-talcott, Hartmut Derendorf, Veronika Butterweck
    Abstract:

    The effect of two varieties of grapefruit juice (white and ruby red) and its selected components (naringin, naringenin, and Bergamottin) was investigated on the activity of the P-glycoprotein (P-gp) in male Sprague−Dawley rats. Talinolol, a nonmetabolized P-gp substrate, was used as a marker compound. The white grapefruit juice (GFJ) had a minor effect on talinolol pharmacokinetics, but the ruby red GFJ reduced the Cmax and the AUC(0−∞) by 60% and 50% of the control, respectively. However, among the GFJ constituents tested, Bergamottin (0.22 mg/kg) was the most potent component augmenting the Cmax and the AUC(0−∞) of talinolol by 2.4- and 1.8-fold, respectively, if compared to the control group. The flavonoids naringenin (0.7 mg/kg) and naringin (2.4 and 9.4 mg/kg) had a similar effect increasing the talinolol Cmax and AUC(0−∞) by 1.5- to 1.8-fold, respectively. In conclusion, the effect of GFJ on P-gp activity seems to depend on the variety, the concentration of compounds in the juice, and the compositio...

  • Effect of grapefruit juice, naringin, naringenin, and Bergamottin on the intestinal carrier-mediated transport of talinolol in rats.
    Journal of agricultural and food chemistry, 2008
    Co-Authors: Whocely Victor De Castro, Susanne U. Mertens-talcott, Hartmut Derendorf, Veronika Butterweck
    Abstract:

    The effect of two varieties of grapefruit juice (white and ruby red) and its selected components (naringin, naringenin, and Bergamottin) was investigated on the activity of the P-glycoprotein (P-gp) in male Sprague-Dawley rats. Talinolol, a nonmetabolized P-gp substrate, was used as a marker compound. The white grapefruit juice (GFJ) had a minor effect on talinolol pharmacokinetics, but the ruby red GFJ reduced the C max and the AUC (0-infinity) by 60% and 50% of the control, respectively. However, among the GFJ constituents tested, Bergamottin (0.22 mg/kg) was the most potent component augmenting the C max and the AUC (0-infinity) of talinolol by 2.4- and 1.8-fold, respectively, if compared to the control group. The flavonoids naringenin (0.7 mg/kg) and naringin (2.4 and 9.4 mg/kg) had a similar effect increasing the talinolol C max and AUC (0-infinity) by 1.5- to 1.8-fold, respectively. In conclusion, the effect of GFJ on P-gp activity seems to depend on the variety, the concentration of compounds in the juice, and the composition of different ingredients.

  • grapefruit juice drug interactions grapefruit juice and its components inhibit p glycoprotein abcb1 mediated transport of talinolol in caco 2 cells
    Journal of Pharmaceutical Sciences, 2007
    Co-Authors: Whocely Victor De Castro, Hartmut Derendorf, Susanne U Mertenstalcott, Veronika Butterweck
    Abstract:

    To investigate the potential interaction between selected ingredients of grapefruit juice and, the transport of talinolol, a P-gp substrate, across Caco-2 cells monolayers was determined in the absence and presence of distinct concentrations of grapefruit juice, Bergamottin, 6',7'-dihydroxyBergamottin, 6',7'-epoxyBergamottin, naringin, and naringenin. Talinolol permeability was selectively inhibited by grapefruit juice and its components. The furano coumarin, 6',7'-epoxyBergamottin, was the most potent inhibitor (IC(50) = 0.7 microM), followed by 6',7'-dihydroxyBergamottin (IC(50) = 34 microM) and Bergamottin that did not show any inhibition at concentrations up to 10 microM. The flavonoid aglycone naringenin was around 10-fold more potent than its glycoside naringin with IC(50) values of 236 and 2409 microM, respectively. The flavonoids and furanocoumarins tested in this study are in the same range of concentration they are present in the juice contributing, therefore, for the overall inhibitory effect of GFJ on P-gp activity. The in vitro data suggest that compounds present in grapefruit juice are able to inhibit the P-gp activity modifying the disposition of drugs that are P-gp substrates such as talinolol.

  • Grapefruit juice-drug interactions: Grapefruit juice and its components inhibit P-glycoprotein (ABCB1) mediated transport of talinolol in Caco-2 cells.
    Journal of pharmaceutical sciences, 2007
    Co-Authors: Whocely Victor De Castro, Susanne U. Mertens-talcott, Hartmut Derendorf, Veronika Butterweck
    Abstract:

    ABSTRACT To investigate the potential interaction between selected ingredients of grapefruit juice and, the transport of talinolol, a P‐gp substrate, across Caco‐2 cells monolayers was determined in the absence and presence of distinct concentrations of grapefruit juice, Bergamottin, 6′,7′‐dihydroxyBergamottin, 6′,7′‐epoxyBergamottin, naringin, and naringenin. Talinolol permeability was selectively inhibited by grapefruit juice and its components. The furano coumarin, 6′,7′‐epoxyBergamottin, was the most potent inhibitor (IC 50 = 0.7 µM), followed by 6′,7′‐dihydroxyBergamottin (IC 50 = 34 µM) and Bergamottin that did not show any inhibition at concentrations up to 10 µM. The flavonoid aglycone naringenin was around 10‐fold more potent than its glycoside naringin with IC 50 values of 236 and 2409 µM, respectively. The flavonoids and furanocoumarins tested in this study are in the same range of concentration they are present in the juice contributing, therefore, for the overall inhibitory effect of GFJ on P‐gp activity. The in vitro data suggest that compounds present in grapefruit juice are able to inhibit the P‐gp activity modifying the disposition of drugs that are P‐gp substrates such as talinolol. © 2007 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 2808–2817, 2007

  • variation of flavonoids and furanocoumarins in grapefruit juices a potential source of variability in grapefruit juice drug interaction studies
    Journal of Agricultural and Food Chemistry, 2006
    Co-Authors: Whocely Victor De Castro, Veronika Butterweck, Susanne U Mertenstalcott, Anke Rubner, Hartmut Derendorf
    Abstract:

    Grapefruit juice (GFJ) has been found to interact with several medications, increasing their oral bioavailability and the risk of toxicity. Inhibition of CYP3A4 in the small intestine by flavonoids (such as naringin and naringenin) and furanocoumarins (including Bergamottin and 6‘,7‘-dihydroxyBergamottin) present in GFJ seems to be the predominant mechanism, although P-glycoprotein and influx transporters in the small intestine are also involved. The quantity of interactive compounds ingested may affect the magnitude and mechanism of the food−drug interaction. Therefore, these four compounds were quantified by HPLC analysis in commercially available and fresh-squeezed GFJ and in grapefruit tissues. Considerable variability in naringin (174−1492 μmol/L), Bergamottin (1.0−36.6 μmol/L), and 6‘,7‘-dihydroxyBergamottin (0.22−52.5 μmol/L) was observed, whereas naringenin could not be detected. White grapefruit showed higher concentrations of naringin and furanocoumarins located in the albedo and flavedo compare...

Hartmut Derendorf - One of the best experts on this subject based on the ideXlab platform.

  • Effect of grapefruit juice, naringin, naringenin, and Bergamottin on the intestinal carrier-mediated transport of talinolol in rats.
    Journal of agricultural and food chemistry, 2008
    Co-Authors: Whocely Victor De Castro, Susanne U. Mertens-talcott, Hartmut Derendorf, Veronika Butterweck
    Abstract:

    The effect of two varieties of grapefruit juice (white and ruby red) and its selected components (naringin, naringenin, and Bergamottin) was investigated on the activity of the P-glycoprotein (P-gp) in male Sprague−Dawley rats. Talinolol, a nonmetabolized P-gp substrate, was used as a marker compound. The white grapefruit juice (GFJ) had a minor effect on talinolol pharmacokinetics, but the ruby red GFJ reduced the Cmax and the AUC(0−∞) by 60% and 50% of the control, respectively. However, among the GFJ constituents tested, Bergamottin (0.22 mg/kg) was the most potent component augmenting the Cmax and the AUC(0−∞) of talinolol by 2.4- and 1.8-fold, respectively, if compared to the control group. The flavonoids naringenin (0.7 mg/kg) and naringin (2.4 and 9.4 mg/kg) had a similar effect increasing the talinolol Cmax and AUC(0−∞) by 1.5- to 1.8-fold, respectively. In conclusion, the effect of GFJ on P-gp activity seems to depend on the variety, the concentration of compounds in the juice, and the compositio...

  • Effect of grapefruit juice, naringin, naringenin, and Bergamottin on the intestinal carrier-mediated transport of talinolol in rats.
    Journal of agricultural and food chemistry, 2008
    Co-Authors: Whocely Victor De Castro, Susanne U. Mertens-talcott, Hartmut Derendorf, Veronika Butterweck
    Abstract:

    The effect of two varieties of grapefruit juice (white and ruby red) and its selected components (naringin, naringenin, and Bergamottin) was investigated on the activity of the P-glycoprotein (P-gp) in male Sprague-Dawley rats. Talinolol, a nonmetabolized P-gp substrate, was used as a marker compound. The white grapefruit juice (GFJ) had a minor effect on talinolol pharmacokinetics, but the ruby red GFJ reduced the C max and the AUC (0-infinity) by 60% and 50% of the control, respectively. However, among the GFJ constituents tested, Bergamottin (0.22 mg/kg) was the most potent component augmenting the C max and the AUC (0-infinity) of talinolol by 2.4- and 1.8-fold, respectively, if compared to the control group. The flavonoids naringenin (0.7 mg/kg) and naringin (2.4 and 9.4 mg/kg) had a similar effect increasing the talinolol C max and AUC (0-infinity) by 1.5- to 1.8-fold, respectively. In conclusion, the effect of GFJ on P-gp activity seems to depend on the variety, the concentration of compounds in the juice, and the composition of different ingredients.

  • grapefruit juice drug interactions grapefruit juice and its components inhibit p glycoprotein abcb1 mediated transport of talinolol in caco 2 cells
    Journal of Pharmaceutical Sciences, 2007
    Co-Authors: Whocely Victor De Castro, Hartmut Derendorf, Susanne U Mertenstalcott, Veronika Butterweck
    Abstract:

    To investigate the potential interaction between selected ingredients of grapefruit juice and, the transport of talinolol, a P-gp substrate, across Caco-2 cells monolayers was determined in the absence and presence of distinct concentrations of grapefruit juice, Bergamottin, 6',7'-dihydroxyBergamottin, 6',7'-epoxyBergamottin, naringin, and naringenin. Talinolol permeability was selectively inhibited by grapefruit juice and its components. The furano coumarin, 6',7'-epoxyBergamottin, was the most potent inhibitor (IC(50) = 0.7 microM), followed by 6',7'-dihydroxyBergamottin (IC(50) = 34 microM) and Bergamottin that did not show any inhibition at concentrations up to 10 microM. The flavonoid aglycone naringenin was around 10-fold more potent than its glycoside naringin with IC(50) values of 236 and 2409 microM, respectively. The flavonoids and furanocoumarins tested in this study are in the same range of concentration they are present in the juice contributing, therefore, for the overall inhibitory effect of GFJ on P-gp activity. The in vitro data suggest that compounds present in grapefruit juice are able to inhibit the P-gp activity modifying the disposition of drugs that are P-gp substrates such as talinolol.

  • Grapefruit juice-drug interactions: Grapefruit juice and its components inhibit P-glycoprotein (ABCB1) mediated transport of talinolol in Caco-2 cells.
    Journal of pharmaceutical sciences, 2007
    Co-Authors: Whocely Victor De Castro, Susanne U. Mertens-talcott, Hartmut Derendorf, Veronika Butterweck
    Abstract:

    ABSTRACT To investigate the potential interaction between selected ingredients of grapefruit juice and, the transport of talinolol, a P‐gp substrate, across Caco‐2 cells monolayers was determined in the absence and presence of distinct concentrations of grapefruit juice, Bergamottin, 6′,7′‐dihydroxyBergamottin, 6′,7′‐epoxyBergamottin, naringin, and naringenin. Talinolol permeability was selectively inhibited by grapefruit juice and its components. The furano coumarin, 6′,7′‐epoxyBergamottin, was the most potent inhibitor (IC 50 = 0.7 µM), followed by 6′,7′‐dihydroxyBergamottin (IC 50 = 34 µM) and Bergamottin that did not show any inhibition at concentrations up to 10 µM. The flavonoid aglycone naringenin was around 10‐fold more potent than its glycoside naringin with IC 50 values of 236 and 2409 µM, respectively. The flavonoids and furanocoumarins tested in this study are in the same range of concentration they are present in the juice contributing, therefore, for the overall inhibitory effect of GFJ on P‐gp activity. The in vitro data suggest that compounds present in grapefruit juice are able to inhibit the P‐gp activity modifying the disposition of drugs that are P‐gp substrates such as talinolol. © 2007 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 2808–2817, 2007

  • variation of flavonoids and furanocoumarins in grapefruit juices a potential source of variability in grapefruit juice drug interaction studies
    Journal of Agricultural and Food Chemistry, 2006
    Co-Authors: Whocely Victor De Castro, Veronika Butterweck, Susanne U Mertenstalcott, Anke Rubner, Hartmut Derendorf
    Abstract:

    Grapefruit juice (GFJ) has been found to interact with several medications, increasing their oral bioavailability and the risk of toxicity. Inhibition of CYP3A4 in the small intestine by flavonoids (such as naringin and naringenin) and furanocoumarins (including Bergamottin and 6‘,7‘-dihydroxyBergamottin) present in GFJ seems to be the predominant mechanism, although P-glycoprotein and influx transporters in the small intestine are also involved. The quantity of interactive compounds ingested may affect the magnitude and mechanism of the food−drug interaction. Therefore, these four compounds were quantified by HPLC analysis in commercially available and fresh-squeezed GFJ and in grapefruit tissues. Considerable variability in naringin (174−1492 μmol/L), Bergamottin (1.0−36.6 μmol/L), and 6‘,7‘-dihydroxyBergamottin (0.22−52.5 μmol/L) was observed, whereas naringenin could not be detected. White grapefruit showed higher concentrations of naringin and furanocoumarins located in the albedo and flavedo compare...

Ock K. Chun - One of the best experts on this subject based on the ideXlab platform.

  • furocoumarin kinetics in plasma and urine of healthy adults following consumption of grapefruit citrus paradisi macf and grapefruit juice
    Journal of Agricultural and Food Chemistry, 2017
    Co-Authors: Melissa M Melough, Sang Gil Lee, Terrence M. Vance, Christopher Perkins, Anthony A. Provatas, Abrar A. Qureshi, Eunyoung Cho, Ock K. Chun
    Abstract:

    Furocoumarins are a class of organic compounds found in a variety of vegetables and fruits. Relatively little is known about the absorption and excretion of these compounds following ingestion. The objective of this study was to identify furocoumarins in grapefruit and grapefruit juice and observe their kinetics in blood and urine. The furocoumarins detected in grapefruit using UPLC-MS/MS were Bergamottin, 6′,7′-dihydroxyBergamottin (6′,7′-DHB), epoxyBergamottin, and bergaptol. Bergamottin, 6′,7′-DHB, bergaptol, and bergapten were detected in grapefruit juice. In this study of 6 males and 3 females, only Bergamottin and 6′,7′-DHB were detected in plasma, whereas in urine, four distinct furocoumarin metabolites as well as bergaptol, 6′,7′-DHB, 8-methoxypsoralen (8-MOP), Bergamottin, and psoralen were identified. Following grapefruit ingestion, furocoumarins were detectable in plasma as early as 15 min and in urine within 1 h. They remained in plasma for up to 3 or more hours and in urine as late as 24 h.

  • development of a comprehensive analytical method for furanocoumarins in grapefruit and their metabolites in plasma and urine using uplc ms ms a preliminary study
    International Journal of Food Sciences and Nutrition, 2016
    Co-Authors: Sang Gil Lee, Kijoon Kim, Terrence M. Vance, Christopher Perkins, Anthony A. Provatas, Abrar A. Qureshi, Eunyoung Cho, Ock K. Chun
    Abstract:

    To develop a comprehensive analytical method for photoactive furanocoumarins, grapefruit (whole, flesh, peel and juice) was extracted using QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) method. Seven furanocoumarins: bergaptol, psoralen, 8-methoxypsoralen, bergapten, 6',7'-dihydroxyBergamottin (6',7'-DHB), epoxyBergamottin and Bergamottin were determined in grapefruit using UPLC-MS/MS. The concentrations of furanocoumarins in the plasma and urine of six healthy young adults before and after ingestion of grapefruit or grapefruit juice were also determined. Recovery rates of furanocoumarins by QuEChERS method from matrix spike sample and laboratory calibrate sample were 125.7 ± 25.4% and 105.7 ± 6.3%, respectively. Bergamottin and 6',7'-DHB were predominant compounds in grapefruit flesh, juice and plasma, while bergaptol and 6',7'-DHB were major compounds detected in the urine. The results demonstrated that Bergamottin and 6',7'-DHB were metabolized to bergaptol. Overall, the analytical methods developed in the present study can be applied to the analysis of various furanocoumarins in plant sources and biological samples.

  • Bioavailability of furocoumarins after ingestion of grapefruit or grapefruit juice
    The FASEB Journal, 2015
    Co-Authors: Sang Gil Lee, Kijoon Kim, Terrence M. Vance, Christopher Perkins, Anthony A. Provatas, Abrar A. Qureshi, Eunyoung Cho, Ock K. Chun
    Abstract:

    Furocoumarins are photoactive compounds that may cause phytophotodermatitis and are abundant in grapefruit. However, little is known about the distribution of furocoumarins in fresh grapefruit and commercial grapefruit juices. Furthermore, the fate of grapefruit furocoumarins in humans is largely unknown. Thus, seven furocoumarins: bergaptol, psoralen, 8-methoxypsoralen (8-MOP), bergapten, 6',7'-dihydroxyBergamottin (6',7'-DHB), epoxyBergamottin, and Bergamottin in grapefruit (whole, flesh, and peel) and grapefruit juice were measured using UPLC-MS/MS. We also measured the concentration of furocoumarins from the plasma of 6 healthy young-adult subjects before and at 90 and 180 min after consumption of grapefruit (600 g, n=3) or grapefruit juice (474 ml, n=3). Six compounds in grapefruit or juice were detected but 8-MOP was not detectable. Peel contained more furocoumarins than flesh in grapefruit. Bergamottin and 6',7'-DHB were predominant compounds in flesh and juice. In plasma, Bergamottin and 6',7'-DHB...