SYNTHETIC FLAVONOIDS CROSS THE PLACENTA IN THE RAT AND ARE FOUND IN FETAL BRAIN

The synthetic flavonoid EMD-49209 is a potent inhibitor of the in vivo and in vitro binding of thyroxine (T-4) to transthyretin (TTR). We st udied the distribution of I-125-labeled EMD-49209 in maternal tissues, intestinal contents, and fetal tissues in rats that were 20 days preg nant (from 1 to 24 h after intravenous injection). The percent dose of EMD decreased quickly with time. In maternal brain no radioactive fla vonoid could be detected. EMD was excreted very rapidly from the intes tines. In the fetal compartment the percent dose of EMD increased with time; after 24 h it contained 17% of the EMD. The flavonoid was found in all fetal tissues investigated and also in the fetal brain. Becaus e TTR concentrations are high in the fetal rat, especially in the brai n, the transfer of flavonoid to the fetal brain might be linked to TTR expression. The presence of flavonoid in the fetal brain raises the p ossibility of an essential interference of flavonoids with the availab lity of T-4 in the fetal compartment.