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Mol Nutr Food Res. 2018 Sep;62(18):e1700916. doi: 10.1002/mnfr.201700916. Epub 2018 Feb 12.

Isothiocyanates and Xenobiotic Detoxification.

Author information

1
Laboratory of Molecular Biomedicine, Institute of Bioscience, Laboratory of Food Safety and Food Integrity, Institute of Tropical Agriculture and Food Security, Faculty of Food Science and Technology, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
2
Food Science Technology Program, School of Agro-Industry, Mae Fah Luang University, Chiang Rai, Thailand.
3
Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK.

Abstract

The potential of isothiocyanates to antagonize the carcinogenicity of structurally diverse chemicals has been established in animals. A feasible mechanism of action involves protecting DNA by reducing the availability of the genotoxic metabolites of chemical carcinogens by either inhibiting their generation and/or stimulating their detoxification. In vivo as well as in vitro studies conducted in rat/human primary hepatocytes and precision-cut tissue slices have revealed that isothiocyanates can impair cytochrome P450 activity, including the CYP1 family which is the most active in the bioactivation of carcinogens, by virtue of being mechanism-based inactivators. The aromatic phenethyl isothiocyanate is the most effective of those studied, whereas aliphatic isothiocyanates such as sulforaphane and erucin necessitate high doses in order to manifest such effects that may not always be achievable through the diet. In all systems studied, isothiocyanates are strong inducers of detoxification enzyme systems including quinone reductase, glutathione S-transferase, epoxide hydrolase, and UDP-glucuronosyl transferase. Indeed, in smokers phenethyl isothiocyanate intake increases the urinary excretion of inactive mercapturate metabolites of toxic chemicals present in tobacco. Glucosinolates, the precursors of isothiocyanates, have also the potential to upregulate detoxification enzyme systems, but their contribution to the cancer chemoprevention linked to cruciferous vegetable consumption remains to be evaluated.

KEYWORDS:

cancer chemoprevention; cytochromes P450; detoxification; glucosinolates; isothiocyanates

PMID:
29288567
DOI:
10.1002/mnfr.201700916
[Indexed for MEDLINE]

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