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4-Methylsulfanyl-3-butenyl isothiocyanate derived from glucoraphasatin is a potent inducer of rat hepatic phase II enzymes and a potential chemopreventive agent

  • Toxicokinetics and Metabolism
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Abstract

The objective of this study was to establish whether the phytochemical glucoraphasatin, a glucosinolate present in cruciferous vegetables, and its corresponding isothiocyanate, 4-methylsulfanyl-3-butenyl isothiocyanate, up-regulate enzymes involved in the detoxification of carcinogens and are thus potential chemopreventive agents. Glucoraphasatin and myrosinase were isolated and purified from Daikon sprouts and Sinapis alba L., respectively. Glucoraphasatin (0–10 μM) was incubated for 24 h with precision-cut rat liver slices in the presence and absence of myrosinase, the enzyme that converts the glucosinolate to the isothiocyanate. The intact glucosinolate failed to influence the O-dealkylations of methoxy- and ethoxyresorufin or the apoprotein expression of CYP1 enzymes. Supplementation with myrosinase led to an increase in the dealkylation of methoxyresorufin, but only at the highest concentration of the glucosinolate, and CYP1A2 expression. In the absence of myrosinase, glucoraphasatin caused a marked increase in epoxide hydrolase activity at concentrations as low as 1 μM paralleled by a rise in the enzyme protein expression; at the highest concentration only, a rise was also observed in glucuronosyl transferase activity, but other phase II enzyme systems were unaffected. Addition of myrosinase to the glucoraphasatin incubation maintained the rise in epoxide hydrolase and glucuronosyl transferase activities, further elevated quinone reductase and glutathione S-transferase activities, and increased total glutathione concentrations. It is concluded that at low concentrations, glucoraphasatin, either intact and/or through the formation of 4-methylsulfanyl-3-butenyl isothiocyanate, is a potent inducer of hepatic enzymes involved in the detoxification of chemical carcinogens and merits further investigation for chemopreventive activity.

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Acknowledgments

The authors thank the Malaysian Government for funding this work through a PhD award to one of them (AF Abdull Razis).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Molecular Toxicology Group, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK

    Ahmed Faizal Abdull Razis & Costas Ioannides

  2. Agricultural Research Council Industrial Crop Research Center (CRA-CIN), Via di Corticella, 133, 40129, Bologna, Italy

    Gina Rosalinda De Nicola, Eleonora Pagnotta & Renato Iori

Authors
  1. Ahmed Faizal Abdull Razis
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  2. Gina Rosalinda De Nicola
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  3. Eleonora Pagnotta
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  4. Renato Iori
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  5. Costas Ioannides
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Correspondence to Costas Ioannides.

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Abdull Razis, A.F., De Nicola, G.R., Pagnotta, E. et al. 4-Methylsulfanyl-3-butenyl isothiocyanate derived from glucoraphasatin is a potent inducer of rat hepatic phase II enzymes and a potential chemopreventive agent. Arch Toxicol 86, 183–194 (2012). https://doi.org/10.1007/s00204-011-0750-x

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  • DOI: https://doi.org/10.1007/s00204-011-0750-x

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