title: Pharmacokinetics, Tissue Distribution, and Anti-Lipogenic/Adipogenic Effects of Allyl-Isothiocyanate Metabolites.
abstract: Allyl-isothiocyanate (AITC) is an organosulfur phytochemical found in abundance in common cruciferous vegetables such as mustard, wasabi, and cabbage. Although AITC is metabolized primarily through the mercapturic acid pathway, its exact pharmacokinetics remains undefined and the biological function of AITC metabolites is still largely unknown. In this study, we evaluated the inhibitory effects of AITC metabolites on lipid accumulation in vitro and elucidated the pharmacokinetics and tissue distribution of AITC metabolites in rats. We found that AITC metabolites generally conjugate with glutathione (GSH) or N-acetylcysteine (NAC) and are distributed in most organs and tissues. Pharmacokinetic analysis showed a rapid uptake and complete metabolism of AITC following oral administration to rats. Although AITC has been reported to exhibit anti-tumor activity in bladder cancer, the potential bioactivity of its metabolites has not been explored. We found that GSH-AITC and NAC-AITC effectively inhibit adipogenic differentiation of 3T3-L1 preadipocytes and suppress expression of PPAR-γ, C/EBPα, and FAS, which are up-regulated during adipogenesis. GSH-AITC and NAC-AITC also suppressed oleic acid-induced lipid accumulation and lipogenesis in hepatocytes. Our findings suggest that AITC is almost completely metabolized in the liver and rapidly excreted in urine through the mercapturic acid pathway following administration in rats. AITC metabolites may exert anti-obesity effects through suppression of adipogenesis or lipogenesis.
authors: Department of Food Biotechnology, Korea University of Science and Technology, Seongnam 463-746, Republic of Korea.
authors: Yang-Ji
authors: YJ
authors: Kim
authors: Department of Food Biotechnology, Korea University of Science and Technology, Seongnam 463-746, Republic of Korea.
authors: Da-Hye
authors: DH
authors: Lee
authors: Department of Food Biotechnology, Korea University of Science and Technology, Seongnam 463-746, Republic of Korea; Metabolic Mechanism Research Group, Korea Food Research Institute, Seongnam 463-746, Republic of Korea.
authors: Jiyun
authors: J
authors: Ahn
authors: Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors: Woo-Jae
authors: WJ
authors: Chung
authors: Metabolic Mechanism Research Group, Korea Food Research Institute, Seongnam 463-746, Republic of Korea.
authors: Young Jin
authors: YJ
authors: Jang
authors: Metabolic Mechanism Research Group, Korea Food Research Institute, Seongnam 463-746, Republic of Korea.
authors: Ki-Seung
authors: KS
authors: Seong
authors: Department of Food Science & Technology, Chonnam National University, Gwangju 500-757, Republic of Korea.
authors: Jae-Hak
authors: JH
authors: Moon
authors: Department of Food Biotechnology, Korea University of Science and Technology, Seongnam 463-746, Republic of Korea; Metabolic Mechanism Research Group, Korea Food Research Institute, Seongnam 463-746, Republic of Korea.
authors: Tae Youl
authors: TY
authors: Ha
authors: Department of Food Biotechnology, Korea University of Science and Technology, Seongnam 463-746, Republic of Korea; Metabolic Mechanism Research Group, Korea Food Research Institute, Seongnam 463-746, Republic of Korea.
authors: Chang Hwa
authors: CH
authors: Jung
mesh_terms: D016475:3T3 Cells; D000111:Acetylcysteine / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects*; D000284:Administration, Oral; D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D017879:Isothiocyanates / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000652:urine; D050356:Lipid Metabolism / Q000187:drug effects*; D050155:Lipogenesis / Q000187:drug effects*; D008297:Male; D051379:Mice; D019301:Oleic Acid / Q000494:pharmacology; D051381:Rats; D014018:Tissue Distribution
chemical_list: D017879:Isothiocyanates; D019301:Oleic Acid; C004471:allyl isothiocyanate; D005978:Glutathione; D000111:Acetylcysteine