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Publication : Metabolism and tissue distribution of sulforaphane in Nrf2 knockout and wild-type mice.

First Author  Clarke JD Year  2011
Journal  Pharm Res Volume  28
Issue  12 Pages  3171-9
PubMed ID  21681606 Mgi Jnum  J:303128
Mgi Id  MGI:6511437 Doi  10.1007/s11095-011-0500-z
Citation  Clarke JD, et al. (2011) Metabolism and tissue distribution of sulforaphane in Nrf2 knockout and wild-type mice. Pharm Res 28(12):3171-9
abstractText  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 mumoles) 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 mumole, Nrf2(-/-) genotype had no effect on sulforaphane metabolism. Only Nrf2(-/-) females given 20 mumoles 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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