Induction of Nrf2-mediated cellular defenses and alteration of phase I activities as mechanisms of chemoprotective effects of coffee in the liver
Identifieur interne : 000B27 ( PascalFrancis/Curation ); précédent : 000B26; suivant : 000B28Induction of Nrf2-mediated cellular defenses and alteration of phase I activities as mechanisms of chemoprotective effects of coffee in the liver
Auteurs : C. Cavin [Suisse] ; M. Marin-Kuan [Suisse] ; S. Langouët [France] ; C. Bezencon [Suisse] ; G. Guignard [Suisse] ; C. Verguet [Suisse] ; D. Piguet [Suisse] ; D. Holzh User [Suisse] ; R. Cornaz [Suisse] ; B. Schilter [Suisse]Source :
- Food and chemical toxicology [ 0278-6915 ] ; 2008.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Café.
English descriptors
- KwdEn :
Abstract
Coffee consumption has been associated with a significant decrease in the risk of developing chronic diseases such as Parkinson disease, diabetes type-2 and several types of cancers (e.g. colon, liver). In the present study, a coffee-dependent induction of enzymes involved in xenobiotic detoxification processes was observed in rat liver and primary hepatocytes. In addition, coffee was found to induce the mRNA and protein expression of enzymes involved in cellular antioxidant defenses. These inductions were correlated with the activation of the Nrf2 transcription factor as shown using an ARE-reporter luciferase assay. The induction of detoxifying enzymes GSTs and AKR is compatible with a protection against both genotoxicity and cytotoxicity of aflatoxin B1 (AFB1). This hypothesis was confirmed in in vitro and ex vivo test systems, where coffee reduced both AFB1-DNA and protein adducts. Interestingly, coffee was also found to inhibit cytochrome CYP1A1/2, indicating that other mechanisms different from a stimulation of detoxification may also play a significant role in the chemoprotective effects of coffee. Further investigations in either human liver cell line and primary hepatocytes indicated that the chemoprotective effects of coffee against AFB1 genotoxicity are likely to be of relevance for humans. These data strongly suggest that coffee may protect against the adverse effects of AFB1. In addition, the coffee-mediated stimulation of the Nrf2-ARE pathway resulting in increased endogenous defense mechanisms against electrophilic but also oxidative insults further support that coffee may be associated with a protection against various types of chemical stresses.
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">Induction of Nrf2-mediated cellular defenses and alteration of phase I activities as mechanisms of chemoprotective effects of coffee in the liver</title><author><name sortKey="Cavin, C" sort="Cavin, C" uniqKey="Cavin C" first="C." last="Cavin">C. Cavin</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Quality and Safety Department, Nestlé Research Center, P. 0. Box 44, Vers-chez-les-Blanc</s1><s2>1000 Lausanne</s2><s3>CHE</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Suisse</country></affiliation></author><author><name sortKey="Marin Kuan, M" sort="Marin Kuan, M" uniqKey="Marin Kuan M" first="M." last="Marin-Kuan">M. Marin-Kuan</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Quality and Safety Department, Nestlé Research Center, P. 0. Box 44, Vers-chez-les-Blanc</s1><s2>1000 Lausanne</s2><s3>CHE</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Suisse</country></affiliation></author><author><name sortKey="Langouet, S" sort="Langouet, S" uniqKey="Langouet S" first="S." last="Langouët">S. Langouët</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>INSERM U620, Unirersité de Rennes I, IFR 140, 2 Avenue du Prof. Bernard</s1><s2>35043 Rennes</s2><s3>FRA</s3><sZ>3 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Bezencon, C" sort="Bezencon, C" uniqKey="Bezencon C" first="C." last="Bezencon">C. Bezencon</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Quality and Safety Department, Nestlé Research Center, P. 0. Box 44, Vers-chez-les-Blanc</s1><s2>1000 Lausanne</s2><s3>CHE</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Suisse</country></affiliation></author><author><name sortKey="Guignard, G" sort="Guignard, G" uniqKey="Guignard G" first="G." last="Guignard">G. Guignard</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Quality and Safety Department, Nestlé Research Center, P. 0. Box 44, Vers-chez-les-Blanc</s1><s2>1000 Lausanne</s2><s3>CHE</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Suisse</country></affiliation></author><author><name sortKey="Verguet, C" sort="Verguet, C" uniqKey="Verguet C" first="C." last="Verguet">C. Verguet</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Quality and Safety Department, Nestlé Research Center, P. 0. Box 44, Vers-chez-les-Blanc</s1><s2>1000 Lausanne</s2><s3>CHE</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Suisse</country></affiliation></author><author><name sortKey="Piguet, D" sort="Piguet, D" uniqKey="Piguet D" first="D." last="Piguet">D. Piguet</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Quality and Safety Department, Nestlé Research Center, P. 0. Box 44, Vers-chez-les-Blanc</s1><s2>1000 Lausanne</s2><s3>CHE</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Suisse</country></affiliation></author><author><name sortKey="Holzh User, D" sort="Holzh User, D" uniqKey="Holzh User D" first="D." last="Holzh User">D. Holzh User</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Quality and Safety Department, Nestlé Research Center, P. 0. Box 44, Vers-chez-les-Blanc</s1><s2>1000 Lausanne</s2><s3>CHE</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Suisse</country></affiliation></author><author><name sortKey="Cornaz, R" sort="Cornaz, R" uniqKey="Cornaz R" first="R." last="Cornaz">R. Cornaz</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Quality and Safety Department, Nestlé Research Center, P. 0. Box 44, Vers-chez-les-Blanc</s1><s2>1000 Lausanne</s2><s3>CHE</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Suisse</country></affiliation></author><author><name sortKey="Schilter, B" sort="Schilter, B" uniqKey="Schilter B" first="B." last="Schilter">B. Schilter</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Quality and Safety Department, Nestlé Research Center, P. 0. Box 44, Vers-chez-les-Blanc</s1><s2>1000 Lausanne</s2><s3>CHE</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Suisse</country></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">08-0285055</idno><date when="2008">2008</date><idno type="stanalyst">PASCAL 08-0285055 INIST</idno><idno type="RBID">Pascal:08-0285055</idno><idno type="wicri:Area/PascalFrancis/Corpus">000882</idno><idno type="wicri:Area/PascalFrancis/Curation">000B27</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Induction of Nrf2-mediated cellular defenses and alteration of phase I activities as mechanisms of chemoprotective effects of coffee in the liver</title><author><name sortKey="Cavin, C" sort="Cavin, C" uniqKey="Cavin C" first="C." last="Cavin">C. Cavin</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Quality and Safety Department, Nestlé Research Center, P. 0. Box 44, Vers-chez-les-Blanc</s1><s2>1000 Lausanne</s2><s3>CHE</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Suisse</country></affiliation></author><author><name sortKey="Marin Kuan, M" sort="Marin Kuan, M" uniqKey="Marin Kuan M" first="M." last="Marin-Kuan">M. Marin-Kuan</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Quality and Safety Department, Nestlé Research Center, P. 0. Box 44, Vers-chez-les-Blanc</s1><s2>1000 Lausanne</s2><s3>CHE</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Suisse</country></affiliation></author><author><name sortKey="Langouet, S" sort="Langouet, S" uniqKey="Langouet S" first="S." last="Langouët">S. Langouët</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>INSERM U620, Unirersité de Rennes I, IFR 140, 2 Avenue du Prof. Bernard</s1><s2>35043 Rennes</s2><s3>FRA</s3><sZ>3 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Bezencon, C" sort="Bezencon, C" uniqKey="Bezencon C" first="C." last="Bezencon">C. Bezencon</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Quality and Safety Department, Nestlé Research Center, P. 0. Box 44, Vers-chez-les-Blanc</s1><s2>1000 Lausanne</s2><s3>CHE</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Suisse</country></affiliation></author><author><name sortKey="Guignard, G" sort="Guignard, G" uniqKey="Guignard G" first="G." last="Guignard">G. Guignard</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Quality and Safety Department, Nestlé Research Center, P. 0. Box 44, Vers-chez-les-Blanc</s1><s2>1000 Lausanne</s2><s3>CHE</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Suisse</country></affiliation></author><author><name sortKey="Verguet, C" sort="Verguet, C" uniqKey="Verguet C" first="C." last="Verguet">C. Verguet</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Quality and Safety Department, Nestlé Research Center, P. 0. Box 44, Vers-chez-les-Blanc</s1><s2>1000 Lausanne</s2><s3>CHE</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Suisse</country></affiliation></author><author><name sortKey="Piguet, D" sort="Piguet, D" uniqKey="Piguet D" first="D." last="Piguet">D. Piguet</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Quality and Safety Department, Nestlé Research Center, P. 0. Box 44, Vers-chez-les-Blanc</s1><s2>1000 Lausanne</s2><s3>CHE</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Suisse</country></affiliation></author><author><name sortKey="Holzh User, D" sort="Holzh User, D" uniqKey="Holzh User D" first="D." last="Holzh User">D. Holzh User</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Quality and Safety Department, Nestlé Research Center, P. 0. Box 44, Vers-chez-les-Blanc</s1><s2>1000 Lausanne</s2><s3>CHE</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Suisse</country></affiliation></author><author><name sortKey="Cornaz, R" sort="Cornaz, R" uniqKey="Cornaz R" first="R." last="Cornaz">R. Cornaz</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Quality and Safety Department, Nestlé Research Center, P. 0. Box 44, Vers-chez-les-Blanc</s1><s2>1000 Lausanne</s2><s3>CHE</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Suisse</country></affiliation></author><author><name sortKey="Schilter, B" sort="Schilter, B" uniqKey="Schilter B" first="B." last="Schilter">B. Schilter</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Quality and Safety Department, Nestlé Research Center, P. 0. Box 44, Vers-chez-les-Blanc</s1><s2>1000 Lausanne</s2><s3>CHE</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Suisse</country></affiliation></author></analytic><series><title level="j" type="main">Food and chemical toxicology</title><title level="j" type="abbreviated">Food chem. toxicol.</title><idno type="ISSN">0278-6915</idno><imprint><date when="2008">2008</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Food and chemical toxicology</title><title level="j" type="abbreviated">Food chem. toxicol.</title><idno type="ISSN">0278-6915</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Biological activity</term><term>Coffee</term><term>Cytochrome P450</term><term>Glutathione transferase</term><term>Liver</term><term>Mechanism of action</term><term>Organism defense</term><term>Prevention</term><term>Red blood cell</term><term>Toxicity</term><term>Transcription factor</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Défense organisme</term><term>Toxicité</term><term>Activité biologique</term><term>Mécanisme action</term><term>Prévention</term><term>Café</term><term>Foie</term><term>Facteur transcription</term><term>Erythrocyte</term><term>Glutathione transferase</term><term>Cytochrome P450</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Café</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Coffee consumption has been associated with a significant decrease in the risk of developing chronic diseases such as Parkinson disease, diabetes type-2 and several types of cancers (e.g. colon, liver). In the present study, a coffee-dependent induction of enzymes involved in xenobiotic detoxification processes was observed in rat liver and primary hepatocytes. In addition, coffee was found to induce the mRNA and protein expression of enzymes involved in cellular antioxidant defenses. These inductions were correlated with the activation of the Nrf2 transcription factor as shown using an ARE-reporter luciferase assay. The induction of detoxifying enzymes GSTs and AKR is compatible with a protection against both genotoxicity and cytotoxicity of aflatoxin B1 (AFB<sub>1</sub>). This hypothesis was confirmed in in vitro and ex vivo test systems, where coffee reduced both AFB<sub>1</sub>-DNA and protein adducts. Interestingly, coffee was also found to inhibit cytochrome CYP1A1/2, indicating that other mechanisms different from a stimulation of detoxification may also play a significant role in the chemoprotective effects of coffee. Further investigations in either human liver cell line and primary hepatocytes indicated that the chemoprotective effects of coffee against AFB<sub>1</sub> genotoxicity are likely to be of relevance for humans. These data strongly suggest that coffee may protect against the adverse effects of AFB<sub>1</sub>. In addition, the coffee-mediated stimulation of the Nrf2-ARE pathway resulting in increased endogenous defense mechanisms against electrophilic but also oxidative insults further support that coffee may be associated with a protection against various types of chemical stresses.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0278-6915</s0></fA01><fA02 i1="01"><s0>FCTOD7</s0></fA02><fA03 i2="1"><s0>Food chem. toxicol.</s0></fA03><fA05><s2>46</s2></fA05><fA06><s2>4</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Induction of Nrf2-mediated cellular defenses and alteration of phase I activities as mechanisms of chemoprotective effects of coffee in the liver</s1></fA08><fA09 i1="01" i2="1" l="ENG"><s1>Molecular and Physiological Effects of Bioactive Food Components</s1></fA09><fA11 i1="01" i2="1"><s1>CAVIN (C.)</s1></fA11><fA11 i1="02" i2="1"><s1>MARIN-KUAN (M.)</s1></fA11><fA11 i1="03" i2="1"><s1>LANGOUËT (S.)</s1></fA11><fA11 i1="04" i2="1"><s1>BEZENCON (C.)</s1></fA11><fA11 i1="05" i2="1"><s1>GUIGNARD (G.)</s1></fA11><fA11 i1="06" i2="1"><s1>VERGUET (C.)</s1></fA11><fA11 i1="07" i2="1"><s1>PIGUET (D.)</s1></fA11><fA11 i1="08" i2="1"><s1>HOLZHÄUSER (D.)</s1></fA11><fA11 i1="09" i2="1"><s1>CORNAZ (R.)</s1></fA11><fA11 i1="10" i2="1"><s1>SCHILTER (B.)</s1></fA11><fA12 i1="01" i2="1"><s1>KNASMÜLLER (Siegfried)</s1><s9>ed.</s9></fA12><fA12 i1="02" i2="1"><s1>STIDL (Reinhard)</s1><s9>ed.</s9></fA12><fA12 i1="03" i2="1"><s1>SONTAG (Gerhard)</s1><s9>ed.</s9></fA12><fA12 i1="04" i2="1"><s1>WAGNER (Karl-Heinz)</s1><s9>ed.</s9></fA12><fA14 i1="01"><s1>Quality and Safety Department, Nestlé Research Center, P. 0. Box 44, Vers-chez-les-Blanc</s1><s2>1000 Lausanne</s2><s3>CHE</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>10 aut.</sZ></fA14><fA14 i1="02"><s1>INSERM U620, Unirersité de Rennes I, IFR 140, 2 Avenue du Prof. Bernard</s1><s2>35043 Rennes</s2><s3>FRA</s3><sZ>3 aut.</sZ></fA14><fA15 i1="01"><s1>Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Borschkeagasse 8a</s1><s2>1090 Vienna</s2><s3>AUT</s3><sZ>1 aut.</sZ></fA15><fA15 i1="02"><s1>Department of Analytical Chemistry and Food Chemistry, University of Vienna</s1><s2>Vienna</s2><s3>AUT</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ></fA15><fA15 i1="03"><s1>Institute of Nutritional Sciences, University of Vienna</s1><s2>Vienna</s2><s3>AUT</s3><sZ>4 aut.</sZ></fA15><fA18 i1="01" i2="1"><s1>COST (European Co-operation in Science and Technology</s1><s3>EUR</s3><s9>org-cong.</s9></fA18><fA20><s1>1239-1248</s1></fA20><fA21><s1>2008</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>10616</s2><s5>354000173670880040</s5></fA43><fA44><s0>0000</s0><s1>© 2008 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>1 p.1/4</s0></fA45><fA47 i1="01" i2="1"><s0>08-0285055</s0></fA47><fA60><s1>P</s1><s2>C</s2></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Food and chemical toxicology</s0></fA64><fA66 i1="01"><s0>GBR</s0></fA66><fC01 i1="01" l="ENG"><s0>Coffee consumption has been associated with a significant decrease in the risk of developing chronic diseases such as Parkinson disease, diabetes type-2 and several types of cancers (e.g. colon, liver). In the present study, a coffee-dependent induction of enzymes involved in xenobiotic detoxification processes was observed in rat liver and primary hepatocytes. In addition, coffee was found to induce the mRNA and protein expression of enzymes involved in cellular antioxidant defenses. These inductions were correlated with the activation of the Nrf2 transcription factor as shown using an ARE-reporter luciferase assay. The induction of detoxifying enzymes GSTs and AKR is compatible with a protection against both genotoxicity and cytotoxicity of aflatoxin B1 (AFB<sub>1</sub>). This hypothesis was confirmed in in vitro and ex vivo test systems, where coffee reduced both AFB<sub>1</sub>-DNA and protein adducts. Interestingly, coffee was also found to inhibit cytochrome CYP1A1/2, indicating that other mechanisms different from a stimulation of detoxification may also play a significant role in the chemoprotective effects of coffee. Further investigations in either human liver cell line and primary hepatocytes indicated that the chemoprotective effects of coffee against AFB<sub>1</sub> genotoxicity are likely to be of relevance for humans. These data strongly suggest that coffee may protect against the adverse effects of AFB<sub>1</sub>. In addition, the coffee-mediated stimulation of the Nrf2-ARE pathway resulting in increased endogenous defense mechanisms against electrophilic but also oxidative insults further support that coffee may be associated with a protection against various types of chemical stresses.</s0></fC01><fC02 i1="01" i2="X"><s0>002B03</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Défense organisme</s0><s5>02</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Organism defense</s0><s5>02</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Defensa organismo</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Toxicité</s0><s5>03</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Toxicity</s0><s5>03</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Toxicidad</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Activité biologique</s0><s5>05</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Biological activity</s0><s5>05</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Actividad biológica</s0><s5>05</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Mécanisme action</s0><s5>06</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>Mechanism of action</s0><s5>06</s5></fC03><fC03 i1="04" i2="X" l="SPA"><s0>Mecanismo acción</s0><s5>06</s5></fC03><fC03 i1="05" i2="X" l="FRE"><s0>Prévention</s0><s5>08</s5></fC03><fC03 i1="05" i2="X" l="ENG"><s0>Prevention</s0><s5>08</s5></fC03><fC03 i1="05" i2="X" l="SPA"><s0>Prevención</s0><s5>08</s5></fC03><fC03 i1="06" i2="X" l="FRE"><s0>Café</s0><s2>FX</s2><s5>09</s5></fC03><fC03 i1="06" i2="X" l="ENG"><s0>Coffee</s0><s2>FX</s2><s5>09</s5></fC03><fC03 i1="06" i2="X" l="SPA"><s0>Café</s0><s2>FX</s2><s5>09</s5></fC03><fC03 i1="07" i2="X" l="FRE"><s0>Foie</s0><s5>11</s5></fC03><fC03 i1="07" i2="X" l="ENG"><s0>Liver</s0><s5>11</s5></fC03><fC03 i1="07" i2="X" l="SPA"><s0>Hígado</s0><s5>11</s5></fC03><fC03 i1="08" i2="X" l="FRE"><s0>Facteur transcription</s0><s5>12</s5></fC03><fC03 i1="08" i2="X" l="ENG"><s0>Transcription factor</s0><s5>12</s5></fC03><fC03 i1="08" i2="X" l="SPA"><s0>Factor transcripción</s0><s5>12</s5></fC03><fC03 i1="09" i2="X" l="FRE"><s0>Erythrocyte</s0><s5>16</s5></fC03><fC03 i1="09" i2="X" l="ENG"><s0>Red blood cell</s0><s5>16</s5></fC03><fC03 i1="09" i2="X" l="SPA"><s0>Eritrocito</s0><s5>16</s5></fC03><fC03 i1="10" i2="X" l="FRE"><s0>Glutathione transferase</s0><s2>FE</s2><s5>17</s5></fC03><fC03 i1="10" i2="X" l="ENG"><s0>Glutathione transferase</s0><s2>FE</s2><s5>17</s5></fC03><fC03 i1="10" i2="X" l="SPA"><s0>Glutathione transferase</s0><s2>FE</s2><s5>17</s5></fC03><fC03 i1="11" i2="X" l="FRE"><s0>Cytochrome P450</s0><s5>18</s5></fC03><fC03 i1="11" i2="X" l="ENG"><s0>Cytochrome P450</s0><s5>18</s5></fC03><fC03 i1="11" i2="X" l="SPA"><s0>Citocromo P450</s0><s5>18</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Transferases</s0><s2>FE</s2></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Transferases</s0><s2>FE</s2></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Transferases</s0><s2>FE</s2></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Enzyme</s0><s2>FE</s2></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Enzyme</s0><s2>FE</s2></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Enzima</s0><s2>FE</s2></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Appareil digestif</s0><s5>61</s5></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Digestive system</s0><s5>61</s5></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Aparato digestivo</s0><s5>61</s5></fC07><fC07 i1="04" i2="X" l="FRE"><s0>Cellule sanguine</s0><s5>62</s5></fC07><fC07 i1="04" i2="X" l="ENG"><s0>Blood cell</s0><s5>62</s5></fC07><fC07 i1="04" i2="X" l="SPA"><s0>Célula sanguínea</s0><s5>62</s5></fC07><fN21><s1>182</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA><pR><fA30 i1="01" i2="1" l="ENG"><s1>Molecular and Physiological Effects of Bioactive Food Compounds. International conference</s1><s3>Vienna AUT</s3><s4>2006-10-11</s4></fA30></pR></standard></inist></record>Pour manipuler ce document sous Unix (Dilib)
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|texte= Induction of Nrf2-mediated cellular defenses and alteration of phase I activities as mechanisms of chemoprotective effects of coffee in the liver
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