title: Metabolism and tissue distribution of sulforaphane in Nrf2 knockout and wild-type mice.
abstract: OBJECTIVE
  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.
authors.affiliation: Molecular and Cellular Biology Program, Oregon State University, Corvallis, Oregon 97331, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Clarke
authors.forename: Anna
authors.initials: A
authors.lastname: Hsu
authors.forename: David E
authors.initials: DE
authors.lastname: Williams
authors.forename: Roderick H
authors.initials: RH
authors.lastname: Dashwood
authors.forename: Jan F
authors.initials: JF
authors.lastname: Stevens
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Emily
authors.initials: E
authors.lastname: Ho
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000378:metabolism* / Q000493:pharmacokinetics*; D005260:Female; D017879:Isothiocyanates; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000235:genetics*; D013454:Sulfoxides; D013861:Thiocyanates / Q000378:metabolism* / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D016588:Anticarcinogenic Agents; D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; D013454:Sulfoxides; D013861:Thiocyanates; C016766:sulforaphane