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Metabolism and Tissue Distribution of Sulforaphane in Nrf2 Knockout and Wild-Type Mice

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ABSTRACT

Purpose

To determine the metabolism and tissue distribution of the dietary chemoprotective agent sulforaphane following oral administration to wild-type and Nrf2 knockout (Nrf2−/−) mice.

Methods

Male and female wild-type and Nrf2−/− mice were given sulforaphane (5 or 20 μmoles) by oral gavage; plasma, liver, kidney, small intestine, colon, lung, brain and prostate were collected at 2, 6 and 24 h (h). The five major metabolites of sulforaphane were measured in tissues by high performance liquid chromatography coupled with tandem mass spectrometry.

Results

Sulforaphane metabolites were detected in all tissues at 2 and 6 h post gavage, with the highest concentrations in the small intestine, prostate, kidney and lung. A dose-dependent increase in sulforaphane concentrations was observed in all tissues except prostate. At 5 μmole, Nrf2−/− genotype had no effect on sulforaphane metabolism. Only Nrf2−/− females given 20 μmoles sulforaphane for 6 h exhibited a marked increase in tissue sulforaphane metabolite concentrations. The relative abundance of each metabolite was not strikingly different between genders and genotypes.

Conclusions

Sulforaphane is metabolized and reaches target tissues in wild-type and Nrf2−/− mice. These data provide further evidence that sulforaphane is bioavailable and may be an effective dietary chemoprevention agent for several tissue sites.

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Abbreviations

ARE:

antioxidant response element

GSH:

glutathione

GST:

glutathione-S-transferase

Keap1:

kelch-like ECH-associated protein 1

LC-MS/MS:

liquid chromatography-tandem mass spectrometry

Nrf2:

nuclear factor erythroid 2 (NF-E2) related factor 2

PK:

pharmacokinetics

SFN-CG:

SFN-cysteinyl-glycine

SFN-Cys:

SFN-cysteine

SFN-GSH:

SFN-glutathione

SFN-NAC:

SFN-N-acetylcysteine

SI:

small intestine

SFN:

sulforaphane

TBHQ:

tert-butylhydroquinone

TFA:

trifluoroacetic acid

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ACKNOWLEDGMENTS & DISCLOSURES

We gratefully acknowledge Dr. Carmen Wong, Mohaiza Dashwood, Dr. Praveen Rajendran, Lydia Petell, Karin Hardin, Lauren Atwell and Dr. Laura Beaver for help with tissue collection and processing. Thanks to Jeff Morre for assistance with mass spectrometry. This work was supported in part the Environmental Health Science Center at Oregon State University (NIEHS P30 ES00210) and NIH grants (CA090890, CA122906, CA122959).

Author information

Authors and Affiliations

  1. Molecular and Cellular Biology Program, Oregon State University, Corvallis, Oregon, 97331, USA

    John D. Clarke

  2. Department of Nutrition and Exercise Sciences, Oregon State University, Corvallis, Oregon, 97331, USA

    John D. Clarke, Anna Hsu & Emily Ho

  3. Linus Pauling Institute, Oregon State University, Corvallis, Oregon, 97331, USA

    David E. Williams, Roderick H. Dashwood, Jan F. Stevens & Emily Ho

  4. Department of Medical Biochemistry, Tohoku University, Sendai, 980-8575, Japan

    Masayuki Yamamoto

  5. Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, Oregon, 97331, USA

    David E. Williams & Roderick H. Dashwood

  6. Department of Pharmaceutical Sciences, Oregon State University, Corvallis, Oregon, 97331, USA

    Jan F. Stevens

  7. Oregon State University, 117 Milam Hall, Corvallis, Oregon, 97331, USA

    Emily Ho

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  1. John D. Clarke
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Correspondence to Emily Ho.

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Clarke, J.D., Hsu, A., Williams, D.E. et al. Metabolism and Tissue Distribution of Sulforaphane in Nrf2 Knockout and Wild-Type Mice. Pharm Res 28, 3171–3179 (2011). https://doi.org/10.1007/s11095-011-0500-z

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  • DOI: https://doi.org/10.1007/s11095-011-0500-z

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