TY - JOUR
T1 - Metabolism and tissue distribution of sulforaphane in Nrf2 knockout and wild-type mice
AU - Clarke, John D.
AU - Hsu, Anna
AU - Williams, David E.
AU - Dashwood, Roderick H.
AU - Stevens, Jan F.
AU - Yamamoto, Masayuki
AU - Ho, Emily
N1 - Funding Information:
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).
PY - 2011/12
Y1 - 2011/12
N2 - 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.
AB - 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.
KW - Nrf2
KW - broccoli
KW - metabolism
KW - sulforaphane
KW - tissue distribution
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U2 - 10.1007/s11095-011-0500-z
DO - 10.1007/s11095-011-0500-z
M3 - Article
C2 - 21681606
AN - SCOPUS:83555173511
SN - 0724-8741
VL - 28
SP - 3171
EP - 3179
JO - Pharmaceutical Research
JF - Pharmaceutical Research
IS - 12
ER -