Glucoraphanin, the bioprecursor of the widely extolled chemopreventive agent sulforaphane found in broccoli, induces Phase-I xenobiotic metabolizing enzymes and increases free radical generation in rat liver

Paolo Perocco, Giorgio Bronzetti, Donatella Canistro, Luca Valgimigli, Andrea Sapone, Alessandra Affatato, Gian Franco Pedulli, Laura Pozzetti, Massimiliano Broccoli, Renato Iori, Jessica Barillari, Valeriana Sblendorio, Marvin S. Legator, Moreno Paolini, Sherif Abdel-Rahman

Research output: Contribution to journalArticle

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Abstract

Epidemiological and animal studies linking high fruit and vegetable consumption to lower cancer risk have strengthened the belief that long-term administration of isolated naturally occurring dietary constituents could reduce the risk of cancer. In recent years, metabolites derived from phytoalexins, such as glucoraphanin found in broccoli and other cruciferous vegetables (Brassicaceae), have gained much attention as potential cancer chemopreventive agents. The protective effect of these micronutrients is assumed to be due to the inhibition of Phase-I carcinogen-bioactivating enzymes and/or induction of Phase-II detoxifying enzymes, an assumption that still remains uncertain. The protective effect of glucoraphanin is thought to be due to sulforaphane, an isothiocyanate metabolite produced from glucoraphanin by myrosinase. Here we show, in rat liver, that while glucoraphanin slightly induces Phase-II enzymes, it powerfully boosts Phase-I enzymes, including activators of polycyclic aromatic hydrocarbons (PAHs), nitrosamines and olefins. Induction of the cytochrome P450 (CYP) isoforms CYP1A1/2, CYP3A1/2 and CYP2E1 was confirmed by Western immunoblotting. CYP induction was paralleled by an increase in the corresponding mRNA levels. Concomitant with this Phase-I induction, we also found that glucoraphanin generated large amount of various reactive radical species, as determined by electron paramagnetic resonance (EPR) spectrometry coupled to a radical-probe technique. This suggests that long-term uncontrolled administration of glucoraphanin could actually pose a potential health hazard.

Original languageEnglish (US)
Pages (from-to)125-136
Number of pages12
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume595
Issue number1-2
DOIs
StatePublished - Mar 20 2006

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Brassica
Xenobiotics
Free Radicals
Liver
Enzymes
Vegetables
Cytochrome P-450 Enzyme System
Enzyme Activators
Brassicaceae
Cytochrome P-450 CYP2E1
Nitrosamines
Neoplasms
Cytochrome P-450 CYP1A1
Enzyme Induction
Micronutrients
Polycyclic Aromatic Hydrocarbons
Electron Spin Resonance Spectroscopy
Alkenes
Carcinogens
sulforafan

Keywords

  • Cancer chemoprevention
  • Cytochrome P450s
  • Free radical species
  • Glucoraphanin
  • Glutathione-S-transferase
  • Isothiocyanates

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Molecular Biology

Cite this

Glucoraphanin, the bioprecursor of the widely extolled chemopreventive agent sulforaphane found in broccoli, induces Phase-I xenobiotic metabolizing enzymes and increases free radical generation in rat liver. / Perocco, Paolo; Bronzetti, Giorgio; Canistro, Donatella; Valgimigli, Luca; Sapone, Andrea; Affatato, Alessandra; Pedulli, Gian Franco; Pozzetti, Laura; Broccoli, Massimiliano; Iori, Renato; Barillari, Jessica; Sblendorio, Valeriana; Legator, Marvin S.; Paolini, Moreno; Abdel-Rahman, Sherif.

In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 595, No. 1-2, 20.03.2006, p. 125-136.

Research output: Contribution to journalArticle

Perocco, Paolo ; Bronzetti, Giorgio ; Canistro, Donatella ; Valgimigli, Luca ; Sapone, Andrea ; Affatato, Alessandra ; Pedulli, Gian Franco ; Pozzetti, Laura ; Broccoli, Massimiliano ; Iori, Renato ; Barillari, Jessica ; Sblendorio, Valeriana ; Legator, Marvin S. ; Paolini, Moreno ; Abdel-Rahman, Sherif. / Glucoraphanin, the bioprecursor of the widely extolled chemopreventive agent sulforaphane found in broccoli, induces Phase-I xenobiotic metabolizing enzymes and increases free radical generation in rat liver. In: Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis. 2006 ; Vol. 595, No. 1-2. pp. 125-136.
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AU - Canistro, Donatella

AU - Valgimigli, Luca

AU - Sapone, Andrea

AU - Affatato, Alessandra

AU - Pedulli, Gian Franco

AU - Pozzetti, Laura

AU - Broccoli, Massimiliano

AU - Iori, Renato

AU - Barillari, Jessica

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AU - Abdel-Rahman, Sherif

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