caa a22 4500 445312548 CHVBK 20180317142635.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s11095-011-0500-z doi (NATIONALLICENCE)springer-10.1007/s11095-011-0500-z Metabolism and Tissue Distribution of Sulforaphane in Nrf2 Knockout and Wild-Type Mice [Elektronische Daten] [John Clarke, Anna Hsu, David Williams, Roderick Dashwood, Jan Stevens, Masayuki Yamamoto, Emily Ho] 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 20μmoles) by oral gavage; plasma, liver, kidney, small intestine, colon, lung, brain and prostate were collected at 2, 6 and 24h (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 6h 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 5μmole, Nrf2−/− genotype had no effect on sulforaphane metabolism. Only Nrf2−/− females given 20μmoles sulforaphane for 6h 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. Springer Science+Business Media, LLC (outside the USA), 2011 broccoli nationallicence metabolism nationallicence Nrf2 nationallicence sulforaphane nationallicence tissue distribution nationallicence ARE : antioxidant response element nationallicence GSH : glutathione nationallicence GST : glutathione-S-transferase nationallicence Keap1 : kelch-like ECH-associated protein 1 nationallicence LC-MS/MS : liquid chromatography-tandem mass spectrometry nationallicence Nrf2 : nuclear factor erythroid 2 (NF-E2) related factor 2 nationallicence PK : pharmacokinetics nationallicence SFN-CG : SFN-cysteinyl-glycine nationallicence SFN-Cys : SFN-cysteine nationallicence SFN-GSH : SFN-glutathione nationallicence SFN-NAC : SFN-N-acetylcysteine nationallicence SI : small intestine nationallicence SFN : sulforaphane nationallicence TBHQ : tert-butylhydroquinone nationallicence TFA : trifluoroacetic acid nationallicence Clarke John Molecular and Cellular Biology Program, Oregon State University, 97331, Corvallis, Oregon, USA aut Hsu Anna Department of Nutrition and Exercise Sciences, Oregon State University, 97331, Corvallis, Oregon, USA aut Williams David Linus Pauling Institute, Oregon State University, 97331, Corvallis, Oregon, USA aut Dashwood Roderick Linus Pauling Institute, Oregon State University, 97331, Corvallis, Oregon, USA aut Stevens Jan Linus Pauling Institute, Oregon State University, 97331, Corvallis, Oregon, USA aut Yamamoto Masayuki Department of Medical Biochemistry, Tohoku University, 980-8575, Sendai, Japan aut Ho Emily Department of Nutrition and Exercise Sciences, Oregon State University, 97331, Corvallis, Oregon, USA aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/12(2011-12-01), 3171-3179 0724-8741 28:12<3171 2011 28 11095 https://doi.org/10.1007/s11095-011-0500-z text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-011-0500-z text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Clarke John Molecular and Cellular Biology Program, Oregon State University, 97331, Corvallis, Oregon, USA aut NATIONALLICENCE 700 1- Hsu Anna Department of Nutrition and Exercise Sciences, Oregon State University, 97331, Corvallis, Oregon, USA aut NATIONALLICENCE 700 1- Williams David Linus Pauling Institute, Oregon State University, 97331, Corvallis, Oregon, USA aut NATIONALLICENCE 700 1- Dashwood Roderick Linus Pauling Institute, Oregon State University, 97331, Corvallis, Oregon, USA aut NATIONALLICENCE 700 1- Stevens Jan Linus Pauling Institute, Oregon State University, 97331, Corvallis, Oregon, USA aut NATIONALLICENCE 700 1- Yamamoto Masayuki Department of Medical Biochemistry, Tohoku University, 980-8575, Sendai, Japan aut NATIONALLICENCE 700 1- Ho Emily Department of Nutrition and Exercise Sciences, Oregon State University, 97331, Corvallis, Oregon, USA aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/12(2011-12-01), 3171-3179 0724-8741 28:12<3171 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer