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  1. Article ; Online: In vitro

    Tong, Zeen / Yerramilli, Usha / Yao, Sylvia / Young, James D / Hoffmann, Matthew / Surapaneni, Sekhar

    Xenobiotica; the fate of foreign compounds in biological systems

    2018  Volume 49, Issue 10, Page(s) 1229–1236

    Abstract: 1. The present study investigated inhibitory effects of enasidenib and its metabolite AGI-16903 on (a) recombinant human nucleoside transporters (hNTs) in hNT- ... ...

    Abstract 1. The present study investigated inhibitory effects of enasidenib and its metabolite AGI-16903 on (a) recombinant human nucleoside transporters (hNTs) in hNT-producing
    MeSH term(s) Aminopyridines/pharmacokinetics ; Aminopyridines/pharmacology ; Animals ; Azacitidine/pharmacokinetics ; Azacitidine/pharmacology ; Cell Line ; Humans ; Isocitrate Dehydrogenase/antagonists & inhibitors ; Nucleoside Transport Proteins/genetics ; Nucleoside Transport Proteins/metabolism ; Triazines/pharmacokinetics ; Triazines/pharmacology ; Xenopus laevis
    Chemical Substances Aminopyridines ; Nucleoside Transport Proteins ; Triazines ; enasidenib (3T1SS4E7AG) ; IDH2 protein, human (EC 1.1.1.41) ; Isocitrate Dehydrogenase (EC 1.1.1.41) ; Azacitidine (M801H13NRU)
    Language English
    Publishing date 2018-11-29
    Publishing country England
    Document type Journal Article
    ZDB-ID 120287-x
    ISSN 1366-5928 ; 0049-8254
    ISSN (online) 1366-5928
    ISSN 0049-8254
    DOI 10.1080/00498254.2018.1539783
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: The interactions of lenalidomide with human uptake and efflux transporters and UDP-glucuronosyltransferase 1A1: lack of potential for drug-drug interactions.

    Tong, Zeen / Yerramilli, Usha / Surapaneni, Sekhar / Kumar, Gondi

    Cancer chemotherapy and pharmacology

    2014  Volume 73, Issue 4, Page(s) 869–874

    Abstract: Purpose: Lenalidomide is an immunomodulatory agent used for the treatment of myelodysplastic syndromes and multiple myeloma. Renal clearance of lenalidomide is the predominant elimination route and is approximately twofold greater than the glomerular ... ...

    Abstract Purpose: Lenalidomide is an immunomodulatory agent used for the treatment of myelodysplastic syndromes and multiple myeloma. Renal clearance of lenalidomide is the predominant elimination route and is approximately twofold greater than the glomerular filtration rate (GFR), suggesting the potential contribution of an active secretory mechanism. In vitro studies were conducted to examine whether lenalidomide is a substrate of drug transporters, namely P-glycoprotein (P-gp), human breast cancer resistance protein (BCRP), multidrug resistance proteins (MRP1, MRP2, MRP3), organic anion transporters (OAT1, OAT3), organic cation transporters (OCT1 and OCT2), human organic cation transporter novel 1 and 2 (OCTN1 and OCTN2), multidrug and toxin extrusion (MATE1) and organic anion transporting polypeptide (OATP1B1). Lenalidomide was also evaluated as an inhibitor of P-gp, BCRP, MRP2, OCT2, OAT1, OAT3, OATP1B1, OATP1B3 and bile salt export pump (BSEP). In addition, inhibition of UDP-glucuronosyltransferase 1A1 (UGT1A1) variants by lenalidomide was also assessed.
    Method: Cells or vesicles expressing each of the human transporters were used for uptake and inhibition studies, with appropriate probe substrates and known inhibitors.
    Results: Results of these studies indicate that the lenalidomide is not a substrate for the transporters examined, except that it is weak substrate of P-gp. None of the transporters studied were inhibited by lenalidomide. Lenalidomide is not an inhibitor of UGT1A1*1/*1 or its polymorphic variants UGT1A1*1/*28 and UGT1A1*28/*28.
    Conclusions: Drug interactions are unlikely to occur when lenalidomide is co-administered with substrates or inhibitors of these transporters. In addition, lenalidomide is unlikely to cause interactions when co-administered with substrates of UGT1A1.
    MeSH term(s) ATP Binding Cassette Transporter, Sub-Family G, Member 2 ; ATP-Binding Cassette Transporters/metabolism ; ATP-Binding Cassette, Sub-Family B, Member 1/metabolism ; Angiogenesis Inhibitors/pharmacokinetics ; Drug Interactions ; Glucuronosyltransferase/metabolism ; Humans ; Membrane Transport Proteins/metabolism ; Multidrug Resistance-Associated Proteins/metabolism ; Neoplasm Proteins/metabolism ; Organic Anion Transporters/metabolism ; Thalidomide/analogs & derivatives ; Thalidomide/pharmacokinetics
    Chemical Substances ABCG2 protein, human ; ATP Binding Cassette Transporter, Sub-Family G, Member 2 ; ATP-Binding Cassette, Sub-Family B, Member 1 ; Angiogenesis Inhibitors ; Membrane Transport Proteins ; Multidrug Resistance-Associated Proteins ; Neoplasm Proteins ; Organic Anion Transporters ; Thalidomide (4Z8R6ORS6L) ; UGT1A1 enzyme (EC 2.4.1.-) ; Glucuronosyltransferase (EC 2.4.1.17) ; lenalidomide (F0P408N6V4)
    Language English
    Publishing date 2014-04
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 6820-2
    ISSN 1432-0843 ; 0344-5704 ; 0943-9404
    ISSN (online) 1432-0843
    ISSN 0344-5704 ; 0943-9404
    DOI 10.1007/s00280-014-2415-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Absorption, Metabolism, and Excretion, In Vitro Pharmacology, and Clinical Pharmacokinetics of Ozanimod, a Novel Sphingosine 1-Phosphate Receptor Modulator.

    Surapaneni, Sekhar / Yerramilli, Usha / Bai, April / Dalvie, Deepak / Brooks, Jennifer / Wang, Xiaomin / Selkirk, Julie V / Yan, Yingzhuo Grace / Zhang, Peijin / Hargreaves, Richard / Kumar, Gondi / Palmisano, Maria / Tran, Jonathan Q

    Drug metabolism and disposition: the biological fate of chemicals

    2021  Volume 49, Issue 5, Page(s) 405–419

    Abstract: Ozanimod is approved for the treatment of relapsing forms of multiple sclerosis. Absorption, metabolism, and excretion of ozanimod were investigated after a single oral dose of 1.0 mg [ ...

    Abstract Ozanimod is approved for the treatment of relapsing forms of multiple sclerosis. Absorption, metabolism, and excretion of ozanimod were investigated after a single oral dose of 1.0 mg [
    MeSH term(s) Administration, Oral ; Adult ; Animals ; CHO Cells ; Cricetinae ; Cricetulus ; Humans ; Indans/administration & dosage ; Indans/metabolism ; Male ; Middle Aged ; Oxadiazoles/administration & dosage ; Oxadiazoles/metabolism ; Sphingosine 1 Phosphate Receptor Modulators/administration & dosage ; Sphingosine 1 Phosphate Receptor Modulators/metabolism ; Sphingosine-1-Phosphate Receptors/metabolism
    Chemical Substances Indans ; Oxadiazoles ; Sphingosine 1 Phosphate Receptor Modulators ; Sphingosine-1-Phosphate Receptors ; ozanimod (Z80293URPV)
    Language English
    Publishing date 2021-03-04
    Publishing country United States
    Document type Clinical Trial ; Journal Article
    ZDB-ID 186795-7
    ISSN 1521-009X ; 0090-9556
    ISSN (online) 1521-009X
    ISSN 0090-9556
    DOI 10.1124/dmd.120.000220
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Absorption, distribution, metabolism, and excretion of mTOR kinase inhibitor CC-223 in rats, dogs, and humans.

    Tong, Zeen / Atsriku, Christian / Yerramilli, Usha / Wang, Xiaomin / Nissel, Jim / Li, Yan / Surapaneni, Sekhar

    Xenobiotica; the fate of foreign compounds in biological systems

    2017  Volume 49, Issue 1, Page(s) 43–53

    Abstract: 1. The absorption, distribution, metabolism, and excretion of CC-223 were studied following a single oral dose of [ ...

    Abstract 1. The absorption, distribution, metabolism, and excretion of CC-223 were studied following a single oral dose of [
    MeSH term(s) Administration, Oral ; Animals ; Body Fluids/metabolism ; Dogs ; Humans ; Pyrazines/metabolism ; Rats ; TOR Serine-Threonine Kinases/metabolism
    Chemical Substances CC-223 ; Pyrazines ; TOR Serine-Threonine Kinases (EC 2.7.1.1)
    Language English
    Publishing date 2017-12-19
    Publishing country England
    Document type Journal Article
    ZDB-ID 120287-x
    ISSN 1366-5928 ; 0049-8254
    ISSN (online) 1366-5928
    ISSN 0049-8254
    DOI 10.1080/00498254.2017.1413718
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Absorption, distribution, metabolism and excretion of an isocitrate dehydrogenase-2 inhibitor enasidenib in rats and humans.

    Tong, Zeen / Atsriku, Christian / Yerramilli, Usha / Wang, Xiaomin / Li, Yan / Reyes, Josephine / Fan, Bin / Yang, Hua / Hoffmann, Matthew / Surapaneni, Sekhar

    Xenobiotica; the fate of foreign compounds in biological systems

    2018  Volume 49, Issue 2, Page(s) 200–210

    Abstract: 1. The absorption, distribution, metabolism and excretion of enasidenib were studied following a single oral dose of [ ...

    Abstract 1. The absorption, distribution, metabolism and excretion of enasidenib were studied following a single oral dose of [
    MeSH term(s) Aminopyridines/blood ; Aminopyridines/pharmacokinetics ; Aminopyridines/urine ; Animals ; Antineoplastic Agents/blood ; Antineoplastic Agents/pharmacokinetics ; Antineoplastic Agents/urine ; Bile/metabolism ; Chromatography, High Pressure Liquid ; Chromatography, Liquid ; Humans ; Isocitrate Dehydrogenase/antagonists & inhibitors ; Kidney/metabolism ; Liver/metabolism ; Metabolic Networks and Pathways ; Rats ; Tandem Mass Spectrometry ; Triazines/blood ; Triazines/pharmacokinetics ; Triazines/urine
    Chemical Substances AG-221 ; Aminopyridines ; Antineoplastic Agents ; Triazines ; Isocitrate Dehydrogenase (EC 1.1.1.41)
    Language English
    Publishing date 2018-01-22
    Publishing country England
    Document type Journal Article
    ZDB-ID 120287-x
    ISSN 1366-5928 ; 0049-8254
    ISSN (online) 1366-5928
    ISSN 0049-8254
    DOI 10.1080/00498254.2018.1425511
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Micelles from PEO-PPO-PEO block copolymers as nanocontainers for solubilization of a poorly water soluble drug hydrochlorothiazide.

    Kadam, Yogesh / Yerramilli, Usha / Bahadur, Anita / Bahadur, Pratap

    Colloids and surfaces. B, Biointerfaces

    2011  Volume 83, Issue 1, Page(s) 49–57

    Abstract: The effect of molecular characteristics of EO-PO triblock copolymers viz. Pluronic(®) P103 (EO(17)PO(60)PEO(17)), P123 (EO(19)PO(69)EO(19)), and F127 (EO(100)PO(65)EO(100)) on micellar behavior and solubilization of a diuretic drug, hydrochlorothiazide ( ... ...

    Abstract The effect of molecular characteristics of EO-PO triblock copolymers viz. Pluronic(®) P103 (EO(17)PO(60)PEO(17)), P123 (EO(19)PO(69)EO(19)), and F127 (EO(100)PO(65)EO(100)) on micellar behavior and solubilization of a diuretic drug, hydrochlorothiazide (HCT) was investigated. The critical micellization temperatures (CMTs) and size for empty as well as drug loaded micelles are reported. The CMTs and micelle size depended on the hydrophobicity and molecular weight of the copolymer; a decrease in CMT and increase in size was observed on solubilization. The solubilization of the drug hydrochlorothiazide (HCT) in the block copolymer nanoaggregates at different temperatures (28, 37, 45°C), pH (3.7, 5.0, 6.7) and in the presence of added salt (NaCl) was monitored by using UV-vis spectroscopy and solubility data were used to calculate the solubilization characteristics; micelle-water partition coefficient (P) and thermodynamic parameters of solubilization viz. Gibbs free energy (ΔG(s)°), enthalpy (ΔH(s)°) and entropy (ΔS(s)°). The solubility of the drug in copolymer increases with the trend: P103>P123>F127. The solubilized drug decreased the cloud point (CP) of copolymers. Results show that the drug solubility increases in the presence of salt but significantly enhances with the increase in the temperature and at a lower pH in which drug remains in the non-ionized form.
    MeSH term(s) Calibration ; Calorimetry, Differential Scanning ; Hydrochlorothiazide/chemistry ; Hydrodynamics ; Hydrogen-Ion Concentration ; Micelles ; Models, Chemical ; Nanoparticles/chemistry ; Neutron Diffraction ; Particle Size ; Poloxamer/chemistry ; Polyethylene Glycols/chemistry ; Propylene Glycols/chemistry ; Scattering, Small Angle ; Sodium Chloride/chemistry ; Solubility ; Solutions ; Spectroscopy, Fourier Transform Infrared ; Temperature ; Water/chemistry
    Chemical Substances Micelles ; PEO-PPO-PEO ; Propylene Glycols ; Solutions ; Water (059QF0KO0R) ; Hydrochlorothiazide (0J48LPH2TH) ; Poloxamer (106392-12-5) ; Polyethylene Glycols (30IQX730WE) ; Sodium Chloride (451W47IQ8X)
    Language English
    Publishing date 2011-03
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1500523-9
    ISSN 1873-4367 ; 0927-7765
    ISSN (online) 1873-4367
    ISSN 0927-7765
    DOI 10.1016/j.colsurfb.2010.10.041
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Solubilization of poorly water-soluble drug carbamezapine in pluronic micelles: effect of molecular characteristics, temperature and added salt on the solubilizing capacity.

    Kadam, Yogesh / Yerramilli, Usha / Bahadur, Anita

    Colloids and surfaces. B, Biointerfaces

    2009  Volume 72, Issue 1, Page(s) 141–147

    Abstract: The solubilization of a poorly water-soluble antiepileptic drug, carbamazepine (CBZ), in a series of micelle-forming PEO-PPO-PEO block copolymers with combinations of blocks having different molecular weight was studied. The drug solubility and micelle- ... ...

    Abstract The solubilization of a poorly water-soluble antiepileptic drug, carbamazepine (CBZ), in a series of micelle-forming PEO-PPO-PEO block copolymers with combinations of blocks having different molecular weight was studied. The drug solubility and micelle-water partition coefficient (P) were determined using UV-vis spectroscopy. Dynamic light scattering on copolymer solutions was used to measure size and polydispersity of nanoaggregates. Solubilization of carbamezapine increased with the rise in temperature and concentration of block copolymers, but no significant increase was observed with added salt (NaCl). The solubilization is also discussed from a thermodynamics viewpoint, by considering the standard free energy of solubilization (DeltaG degrees ).
    MeSH term(s) Carbamazepine/chemistry ; Micelles ; Particle Size ; Poloxamer/chemistry ; Sodium Chloride/pharmacology ; Solubility/drug effects ; Spectrophotometry, Ultraviolet ; Temperature ; Water/chemistry
    Chemical Substances Micelles ; Water (059QF0KO0R) ; Poloxamer (106392-12-5) ; Carbamazepine (33CM23913M) ; Sodium Chloride (451W47IQ8X)
    Language English
    Publishing date 2009-08-01
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1500523-9
    ISSN 1873-4367 ; 0927-7765
    ISSN (online) 1873-4367
    ISSN 0927-7765
    DOI 10.1016/j.colsurfb.2009.03.027
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: In vivo pharmacokinetics, activation of MAPK signaling and induction of phase II/III drug metabolizing enzymes/transporters by cancer chemopreventive compound BHA in the mice.

    Hu, Rong / Shen, Guoxiang / Yerramilli, Usha Rao / Lin, Wen / Xu, Changjiang / Nair, Sujit / Kong, Ah-Ng Tony

    Archives of pharmacal research

    2006  Volume 29, Issue 10, Page(s) 911–920

    Abstract: Phenolic antioxidant butylated hydroxyanisole (BHA) is a commonly used food preservative with broad biological activities, including protection against chemical-induced carcinogenesis, acute toxicity of chemicals, modulation of macromolecule synthesis ... ...

    Abstract Phenolic antioxidant butylated hydroxyanisole (BHA) is a commonly used food preservative with broad biological activities, including protection against chemical-induced carcinogenesis, acute toxicity of chemicals, modulation of macromolecule synthesis and immune response, induction of phase II detoxifying enzymes, as well as its undesirable potential tumor-promoting activities. Understanding the molecular basis underlying these diverse biological actions of BHA is thus of great importance. Here we studied the pharmacokinetics, activation of signaling kinases and induction of phase II/III drug metabolizing enzymes/transporter gene expression by BHA in the mice. The peak plasma concentration of BHA achieved in our current study after oral administration of 200 mg/kg BHA was around 10 microM. This in vivo concentration might offer some insights for the many in vitro cell culture studies on signal transduction and induction of phase II genes using similar concentrations. The oral bioavailability (F) of BHA was about 43% in the mice. In the mouse liver, BHA induced the expression of phase II genes including NQO-1, HO-1, gamma-GCS, GST-pi and UGT 1A6, as well as some of the phase III transporter genes, such as MRP1 and Slcolb2. In addition, BHA activated distinct mitogen-activated protein kinases (MAPKs), c-Jun N-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), as well as p38, suggesting that the MAPK pathways may play an important role in early signaling events leading to the regulation of gene expression including phase II drug metabolizing and some phase III drug transporter genes. This is the first study to demonstrate the in vivo pharmacokinetics of BHA, the in vivo activation of MAPK signaling proteins, as well as the in vivo induction of Phase II/III drug metabolizing enzymes/transporters in the mouse livers.
    MeSH term(s) Administration, Oral ; Animals ; Antioxidants/administration & dosage ; Antioxidants/metabolism ; Antioxidants/pharmacokinetics ; Area Under Curve ; Biological Availability ; Biological Transport/drug effects ; Butylated Hydroxyanisole/administration & dosage ; Butylated Hydroxyanisole/metabolism ; Butylated Hydroxyanisole/pharmacokinetics ; Chromatography, High Pressure Liquid/methods ; Gene Expression Regulation, Enzymologic/drug effects ; Gene Expression Regulation, Enzymologic/genetics ; Glucuronosyltransferase/genetics ; Half-Life ; Inactivation, Metabolic/genetics ; Injections, Intravenous ; Liver/drug effects ; Liver/metabolism ; MAP Kinase Signaling System/drug effects ; Membrane Transport Proteins/genetics ; Mice ; Multidrug Resistance-Associated Proteins/genetics ; NAD(P)H Dehydrogenase (Quinone) ; NADPH Dehydrogenase/genetics ; Reverse Transcriptase Polymerase Chain Reaction/methods
    Chemical Substances Antioxidants ; Membrane Transport Proteins ; Multidrug Resistance-Associated Proteins ; Butylated Hydroxyanisole (25013-16-5) ; NAD(P)H Dehydrogenase (Quinone) (EC 1.6.5.2) ; Nqo1 protein, mouse (EC 1.6.5.2) ; NADPH Dehydrogenase (EC 1.6.99.1) ; Glucuronosyltransferase (EC 2.4.1.17)
    Language English
    Publishing date 2006-11-07
    Publishing country Korea (South)
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 447623-2
    ISSN 1976-3786 ; 0253-6269
    ISSN (online) 1976-3786
    ISSN 0253-6269
    DOI 10.1007/bf02973914
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Micelles from PEO–PPO–PEO block copolymers as nanocontainers for solubilization of a poorly water soluble drug hydrochlorothiazide

    Kadam, Yogesh / Yerramilli, Usha / Bahadur, Anita / Bahadur, Pratap

    Colloids and Surfaces B: Biointerfaces

    Volume v. 83,, Issue no. 1

    Abstract: The effect of molecular characteristics of EO–PO triblock copolymers viz. Pluronic® P103 (EO₁₇PO₆₀PEO₁₇), P123 (EO₁₉PO₆₉EO₁₉), and F127 (EO₁₀₀PO₆₅EO₁₀₀) on micellar behavior and solubilization of a diuretic drug, hydrochlorothiazide (HCT) was ... ...

    Abstract The effect of molecular characteristics of EO–PO triblock copolymers viz. Pluronic® P103 (EO₁₇PO₆₀PEO₁₇), P123 (EO₁₉PO₆₉EO₁₉), and F127 (EO₁₀₀PO₆₅EO₁₀₀) on micellar behavior and solubilization of a diuretic drug, hydrochlorothiazide (HCT) was investigated. The critical micellization temperatures (CMTs) and size for empty as well as drug loaded micelles are reported. The CMTs and micelle size depended on the hydrophobicity and molecular weight of the copolymer; a decrease in CMT and increase in size was observed on solubilization. The solubilization of the drug hydrochlorothiazide (HCT) in the block copolymer nanoaggregates at different temperatures (28, 37, 45°C), pH (3.7, 5.0, 6.7) and in the presence of added salt (NaCl) was monitored by using UV–vis spectroscopy and solubility data were used to calculate the solubilization characteristics; micelle–water partition coefficient (P) and thermodynamic parameters of solubilization viz. Gibbs free energy (ΔGₛ°), enthalpy (ΔHₛ°) and entropy (ΔSₛ°). The solubility of the drug in copolymer increases with the trend: P103>P123>F127. The solubilized drug decreased the cloud point (CP) of copolymers. Results show that the drug solubility increases in the presence of salt but significantly enhances with the increase in the temperature and at a lower pH in which drug remains in the non-ionized form.
    Keywords Gibbs free energy ; sodium chloride ; drugs ; entropy ; molecular weight ; solubility ; temperature ; colloids ; enthalpy ; composite polymers ; solubilization ; hydrochlorothiazide ; hydrophobicity ; spectroscopy ; pH ; micelles
    Language English
    Document type Article
    ISSN 0927-7765
    Database AGRIS - International Information System for the Agricultural Sciences and Technology

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  10. Article: In vivo pharmacokinetics, activation of MAPK signaling and induction of phase II/III drug metabolizing enzymes/transporters by cancer chemopreventive compound BHA in the mice

    Hu, Rong / Shen, Guoxiang / Yerramilli, Usha Rao / Lin, Wen / Xu, Changjiang / Nair, Sujit / Kong, Ah-Ng Tony

    Archives of pharmacal research

    Volume v. 29,, Issue no. 1

    Abstract: Phenolic antioxidant butylated hydroxyanisole (BHA) is a commonly used food preservative with broad biological activities, including protection against chemical-induced carcinogenesis, acute toxicity of chemicals, modulation of macromolecule synthesis ... ...

    Abstract Phenolic antioxidant butylated hydroxyanisole (BHA) is a commonly used food preservative with broad biological activities, including protection against chemical-induced carcinogenesis, acute toxicity of chemicals, modulation of macromolecule synthesis and immune response, induction of phase II detoxifying enzymes, as well as its undesirable potential tumor-promoting activities. Understanding the molecular basis underlying these diverse biological actions of BHA is thus of great importance. Here we studied the pharmacokinetics, activation of signaling kinases and induction of phase II/III drug metabolizing enzymes/transporter gene expression by BHA in the mice. The peak plasma concentration of BHA achieved in our current study after oral administration of 200 mg/kg BHA was around 10 μM. Thisin vivo concentration might offer some insights for the manyin vitro cell culture studies on signal transduction and induction of phase II genes using similar concentrations. The oral bioavailability (F) of BHA was about 43% in the mice. In the mouse liver, BHA induced the expression of phase II genes including NQO-1, HO-1, γ-GCS, GST-pi and UGT 1A6, as well as some of the phase III transporter genes, such as MRP1 and Slco1b2. In addition, BHA activated distinct mitogen-activated protein kinases (MAPKs), c-Jun N-terminal kinase (JNK), extracellular signal-regulated protein kinase (ERK), as well as p38, suggesting that the MAPK pathways may play an important role in early signaling events leading to the regulation of gene expression including phase II drug metabolizing and some phase III drug transporter genes. This is the first study to demonstrate thein vivo pharmacokinetics of BHA, thein vivo activation of MAPK signaling proteins, as well as thein vivo induction of Phase II/III drug metabolizing enzymes/transporters in the mouse livers.
    Keywords cell culture ; acute toxicity ; drugs ; genes ; bioavailability ; mitogen-activated protein kinase ; signal transduction ; chemoprevention ; gene expression regulation ; metabolic detoxification ; mice ; butylated hydroxyanisole ; transporters ; antioxidants ; carcinogenesis ; liver ; immune response ; gene expression ; pharmacokinetics ; oral administration
    Language English
    Document type Article
    ISSN 0253-6269
    Database AGRIS - International Information System for the Agricultural Sciences and Technology

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