Effects of sulforaphane and its S- and R-enantiomers on the expression and activities of human drug-metabolizing cytochromes P450

Srovnalova, Alzbeta; Vanduchova, Alena; Švécarová, Michaela; Anzenbacherová, Eva; Tománková, Veronika; Anzenbacher, Pavel; Dvořák, Zdeněk

doi:10.1016/j.jff.2015.02.006

Cited by 15 publications

(10 citation statements)

References 38 publications

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“…In primary rat hepatocytes, SFN significantly inhibited CYP1A1/2, CYP3A and CYP2B activities after 24-h treatment [ 6 , 14 ]. In human hepatocytes, SFN caused a marked decrease in CYP2A6, CYP2C9, CYP2D6, and CYP3A4 activity, but the protein expression of these forms remained unchanged, which indicates that the SFN-caused decrease in CYP activity was not due to the down-regulation of CYP protein [ 15 ]. Ten-day oral treatment with SFN (3 mg/kg or 12 mg/kg) caused a significant decrease in rat liver CYP1A2, CYP2B, and CYP3A4 activity, while the protein expression of CYP1A1/2 was markedly elevated and that of CYP2B and CYP3A2 was decreased [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, no changes in the mRNA transcript levels of Cyp1a1 and Cyp1a2 were found in SFN-treated rat hepatocytes [ 6 ]. In primary human hepatocytes treated with SFN 10 μM, no induction in the mRNA expression of Cyp1a1 , Cyp1a2 , Cyp2b6 , Cyp2c9 and Cyp3a4 after 24-h treatment was observed [ 15 ], while a great decrease in Cyp3a4 mRNA after 48-h treatment was reported [ 18 ]. In our experiments, the treatment of rat hepatocytes with BNF led to Cyp1a1 , Cyp1a2 , and Cyp3a mRNA induction, which was diminished by SFN co-administration ( Figure 1 ).…”

Section: Discussionmentioning

confidence: 99%

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Sulforaphane Alters β-Naphthoflavone-Induced Changes in Activity and Expression of Drug-Metabolizing Enzymes in Rat Hepatocytes

et al. 2017

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Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, exerts many beneficial effects on human health such as antioxidant, anti-inflammatory, and anticancer effects. The effect of SFN alone on drug-metabolizing enzymes (DMEs) has been investigated in numerous in vitro and in vivo models, but little is known about the effect of SFN in combination with cytochrome P450 (CYP) inducer. The aim of our study was to evaluate the effect of SFN on the activity and gene expression of selected DMEs in primary cultures of rat hepatocytes treated or non-treated with β-naphthoflavone (BNF), the model CYP1A inducer. In our study, SFN alone did not significantly alter the activity and expression of the studied DMEs, except for the glutathione S-transferase (GSTA1) mRNA level, which was significantly enhanced. Co-treatment of hepatocytes with SFN and BNF led to a substantial increase in sulfotransferase, aldoketoreductase 1C, carbonylreductase 1 and NAD(P)H:quinone oxidoreductase 1 activity and a marked decrease in cytochrome P450 (CYP) Cyp1a1, Cyp2b and Cyp3a4 expression in comparison to the treatment with BNF alone. Sulforaphane is able to modulate the activity and/or expression of DMEs, thus shifting the balance of carcinogen metabolism toward deactivation, which could represent an important mechanism of its chemopreventive activity.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Sulforaphane Alters β-Naphthoflavone-Induced Changes in Activity and Expression of Drug-Metabolizing Enzymes in Rat Hepatocytes

et al. 2017

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“…In subsequent extended studies, when rat hepatocytes were exposed to various isothiocyanates (20–40 μ m ) a differential effect was seen in that activity was impaired by SFN but induced by PEITC and BITC whereas allyl isothiocyanate had no effect, highlighting the importance of the side chain . In human hepatocytes, both sulforaphane enantiomers impaired CYP2D6 and CYP3A4 activities but at high, nonphysiological concentrations (50–400 μ m ) …”

Section: Modulation Of the Bioactivation Of Chemical Carcinogens By Dmentioning

confidence: 96%

Isothiocyanates and Xenobiotic Detoxification

Razis

Konsue

Ioannides

2018

Molecular Nutrition Food Res

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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.

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“…23 A previous publication focused on the differences in the degree of interaction between single studies and cocktail studies and proved that the cocktail approach was an adequate and quantitative evaluation method for drug–drug interactions. 24 In addition, it has been deemed that hepatocytes are the most physiologically relevant in vitro system because they contain complete machinery for drug transport and metabolism. 25 Moreover, hepatocyte systems were reported to be more suitable for measuring the activity of UGTs or the expression of both CYPs and UGTs than human liver microsome in vitro systems.…”

Section: Introductionmentioning

confidence: 99%

Stereoisomers of octahydrocurcumin, the hydrogenated metabolites of curcumin, display stereoselective activity on the CYP2E1 enzyme in L-02 cells

et al. 2023

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Effects of sulforaphane and its S- and R-enantiomers on the expression and activities of human drug-metabolizing cytochromes P450

Cited by 15 publications

References 38 publications

Sulforaphane Alters β-Naphthoflavone-Induced Changes in Activity and Expression of Drug-Metabolizing Enzymes in Rat Hepatocytes

Sulforaphane Alters β-Naphthoflavone-Induced Changes in Activity and Expression of Drug-Metabolizing Enzymes in Rat Hepatocytes

Isothiocyanates and Xenobiotic Detoxification

Stereoisomers of octahydrocurcumin, the hydrogenated metabolites of curcumin, display stereoselective activity on the CYP2E1 enzyme in L-02 cells

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