Modulation of xenobiotic conjugation enzymes by dihydromyricetin in rats

Abstract

Dihydromyricetin, 3,3′,4′,5,5′,7-hexahydroxyflavanone, is a phytochemical occurring in high quantities in tree Hovenia dulcis. This flavanonol is effective in counteracting acute EtOH intoxication and in reducing excessive EtOH consumption. As dihydromyricetin is considered for a potential human use its interactions with biotransformation enzymes should be examined. In general, ingested foreign compounds (xenobiotics) might stimulate expression (induction) of these enzymes and/or inhibit their activities. Usually the metabolism of xenobiotics proceeds via two phases of sequential enzymatic conversion to facilitate their excretion from the body. As xenobiotics biotransformation enzymes of the phase II, sulfo- and N/O-acetyltransferases (SULTs and NATs), are involved in the process of carcinogen activation, their induction/inhibition by dihydromyricetin should be examined. Dihydromyricetin was administered to experimental rats by gastric gavages in three consecutive doses (60 mg/kg body weight/day). The induction of sulfo- and N/O-acetyltransferases was assessed based on the protein levels on Western blots and on their metabolic activity in cytosolic samples of liver, small intestines and colon. Moreover, dihydromyricetin the inhibition of sulfo- and N/O-acetyltransferase mediated activities was examined with recombinant enzymes. Dihydromyricetin induced SULT1A1 activity in all tissues were studied with the exception of small intestines but had no effect on N/O-acetyltransferases. While dihydromyricetin did not affect SULT1A1 specific activity, both NAT1 and NAT2 were effectively inhibited (IC50 <10 μmol dm−3).