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.

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. Research Abstract Details 

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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. Abstract Text:

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

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.

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. Publishing Authors By Initials

R Hu,G Shen,UR Yerramilli,W Lin,C Xu,S Nair,AN Kong,

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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. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Archives of pharmacal research

VOLUME: 29

Page Numbers: 911-20

Journal Abbreviation: Arch. Pharm. Res.

ISSN: 0253-6269

DAY: 3

MONTH: Oct

YEAR: 2006

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. Information

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LANGUAGE: eng

NlmUniqueID: 8000036

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. Keywords Mesh Terms:

KEYWORDS: Reverse Transcriptase Polymerase Chain R

MESH TERMS: methods

Chemical & Substance for Abstract: 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. Information

Substance Name: Glucuronosyltransferase

Registry Number: EC 2.4.1.17

Grant and Affiliation Information for 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.

AFFILIATION: Graduate Program in Pharmaceutical Science, Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.

Country: Korea (South)

AGENCY: United States NCI

GRANT: R01-CA094828

ACRONYM: CA

MEDLINETA: Arch Pharm Res

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