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In VivoPharmacokinetics andRegulation of GeneExpression Profilesby IsothiocyanateSulforaphane in theRat Rong HuVidya HebbarBok-Ryang Kim2004 год

In Vivo Pharmacokinetics and Regulation of Gene Expression Profiles by Isothiocyanate Sulforaphane in the Rat
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Страница публикацииПубликация в OpenAlex
Аннотация: Sulforaphane (SUL) is one member of the isothiocyanate class of cancer chemopreventive compounds that has been shown to be effective in blocking initiation and progression of carcinogenesis. Previously, many studies have shown that SUL can potently induce phase II detoxifying enzymes, which contributes to its chemopreventive functions. In this study, we used 4967 oligonucleotides microarray to assess the genes that are modulated by SUL in in vivo rat livers, as well as time course of expression of these genes. The pharmacokinetics of SUL was assessed after oral dose of 50 μmol of SUL. The plasma concentration occurred at 1 h and peaked around 20 μM at 4 h after dosing and declined with a half-life of about 2.2 h. Analysis of the gene expression data found various clusters of genes that are important in cellular defense mechanisms and cell cycle regulation. The most robust cluster of genes is the metallothionein-like genes (MT-1/2 and MT-1a), which are increased up to 10-fold by 2 to 4 h after SUL dosing. The second cluster of genes is the glutathione S-transferase-A3-like genes, which include aflatoxin B1 aldehyde reductase and aldehyde oxidase. These genes are increased slightly by 4 h and peaked at 12 h. Real-time polymerase chain reaction was performed to authenticate the mRNA expression of some of these genes. In summary, this in vivo study of SUL provides the first clue as to the plasma concentrations of SUL, in vivo mitogen-activated protein kinase activations in rat livers, as well as what other genes are modulated in addition to phase II detoxifying genes. The results from this study may yield better insights for its chemopreventive functions.
Год издания: 2004
Авторы: Rong Hu, Vidya Hebbar, Bok-Ryang Kim, Chi Chen, Bożena Winnik, Brian Buckley, Patricia Soteropoulos, Peter Tolias, Ronald P. Hart, Angela Kong
Издательство: American Society for Pharmacology and Experimental Therapeutics
Источник: Journal of Pharmacology and Experimental Therapeutics
Ключевые слова: Genomics, phytochemicals, and oxidative stress, Glutathione Transferases and Polymorphisms, Selenium in Biological Systems
Другие ссылки: Journal of Pharmacology and Experimental Therapeutics (HTML)
PubMed (HTML)