Metabolism and tissue distribution of sulforaphane in Nrf2 knockout and wild-type mice.
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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 moles) 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 mole, Nrf2(-/-) genotype had no effect on sulforaphane metabolism. Only Nrf2(-/-) females given 20 moles 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.
