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Isothiocyanates and Xenobiotic Detoxification.

Ahmad Faizal Abdull Razis1, Nattaya Konsue2,3, Costas Ioannides3

  • 1Laboratory 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.

Molecular Nutrition & Food Research
|December 31, 2017
PubMed
Summary
This summary is machine-generated.

Isothiocyanates protect DNA from carcinogens by inhibiting toxic metabolite generation and boosting detoxification. Phenethyl isothiocyanate is most effective, while dietary intake of glucosinolates

Keywords:
cancer chemopreventioncytochromes P450detoxificationglucosinolatesisothiocyanates

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Area of Science:

  • Biochemistry
  • Toxicology
  • Cancer Chemoprevention

Background:

  • Isothiocyanates are known to counteract chemical carcinogenicity in animal models.
  • Their mechanism involves protecting DNA from genotoxic metabolites of carcinogens.
  • This protection is achieved by inhibiting metabolite generation and/or enhancing detoxification.

Purpose of the Study:

  • To investigate the role of isothiocyanates in modulating carcinogen metabolism and detoxification.
  • To compare the efficacy of different isothiocyanates, including aromatic and aliphatic types.
  • To explore the impact of isothiocyanates on cytochrome P450 activity and detoxification enzyme systems.

Main Methods:

  • In vivo and in vitro studies using rat/human primary hepatocytes and precision-cut tissue slices.
  • Assessing the effect of isothiocyanates on cytochrome P450 (CYP1 family) activity as mechanism-based inactivators.
  • Evaluating the induction of detoxification enzyme systems such as quinone reductase and glutathione S-transferase.

Main Results:

  • Isothiocyanates impair cytochrome P450 activity, particularly CYP1, which is crucial for carcinogen bioactivation.
  • Phenethyl isothiocyanate demonstrated higher efficacy compared to aliphatic isothiocyanates like sulforaphane and erucin.
  • Isothiocyanates strongly induce detoxification enzymes, leading to increased excretion of detoxified tobacco metabolites in smokers.

Conclusions:

  • Isothiocyanates offer a promising strategy for cancer chemoprevention by interfering with carcinogen metabolism.
  • Phenethyl isothiocyanate is a potent agent, but high doses of aliphatic isothiocyanates may be needed.
  • Further research is needed to evaluate the contribution of dietary glucosinolates to cancer chemoprevention.