Effect of red wine polyphenol dietary supplementation on two phase II enzymes in liver of hyperhomocysteinemic mice

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.