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PLoS One. 2015 Aug 28;10(8):e0132151. doi: 10.1371/journal.pone.0132151. eCollection 2015.

Pharmacokinetics, Tissue Distribution, and Anti-Lipogenic/Adipogenic Effects of Allyl-Isothiocyanate Metabolites.

Author information

1
Department of Food Biotechnology, Korea University of Science and Technology, Seongnam 463-746, Republic of Korea.
2
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.
3
Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
4
Metabolic Mechanism Research Group, Korea Food Research Institute, Seongnam 463-746, Republic of Korea.
5
Department of Food Science & Technology, Chonnam National University, Gwangju 500-757, Republic of Korea.

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.

PMID:
26317351
PMCID:
PMC4552636
DOI:
10.1371/journal.pone.0132151
[Indexed for MEDLINE]
Free PMC Article

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