title: Effect of red wine polyphenol dietary supplementation on two phase II enzymes in liver of hyperhomocysteinemic mice.
abstract: Hyperhomocysteinemia leads to diverse clinical manifestations, notably liver disease. The pathogenicity of homocysteine is believed to be due to its ability to produce oxidative stress. Paraoxonase-1 (Pon1), a phase I xenobiotic-metabolizing enzyme (XME) synthesized by liver with anti-oxidative properties within the circulating system is down regulated in case of hyperhomocysteinemia. In a previous study, we have shown that red wine polyphenol extract (PE) supplementation induces a decrease in plasma homocysteine level and an increase in hepatic Pon1 gene expression concomitant with an increase in hepatic and plasma Pon1 activity in a murine model of hyperhomocysteinemia. In the present study, we analyzed the effect of PE supplementation on two phase II XME: NAD(P)H:quinone oxidoreductase (Nqo1) and arylamine-N-acetyltransferase (Nat) family. We found that hyperhomocysteinemia leads to a decrease of hepatic Nqo1 gene expression and activity with a reversal effect of PE supplementation. We also found that hyperhomocysteinemia-induced decrease of peroxynitrite level is associated with an increase of hepatic total Nat activity mainly due to the Nat2 isoform with a reversal effect of PE supplementation. Our results show a beneficial effect of PE supplementation on two phase II enzymes which are altered in case of hyperhomocysteinemia.
authors.affiliation: Laboratory of Gene Dysregulation and Differentiation, Univ. Paris Diderot-CNRS EAC 4413, Unit of Functional and Adaptive Biology (BFA), 75205 Paris cedex 13, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Noll
authors.forename: Julien
authors.initials: J
authors.lastname: Dairou
authors.forename: Clémentine
authors.initials: C
authors.lastname: Ripoll
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Paul
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Dupret
authors.forename: Jean-Maurice
authors.initials: JM
authors.lastname: Delabar
authors.forename: Fernando
authors.initials: F
authors.lastname: Rodrigues-Lima
authors.forename: Nathalie
authors.initials: N
authors.lastname: Janel
mesh_terms: D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D043303:Aryldialkylphosphatase / Q000235:genetics / Q000378:metabolism; D019587:Dietary Supplements; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D020138:Hyperhomocysteinemia / Q000378:metabolism* / Q000517:prevention & control; D008099:Liver / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D010636:Phenols / Q000494:pharmacology*; D059808:Polyphenols; D014920:Wine / Q000032:analysis*
chemical_list: D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D016660:NAD(P)H Dehydrogenase (Quinone); C491732:Nqo1 protein, mouse; D001191:Arylamine N-Acetyltransferase; D043303:Aryldialkylphosphatase