Flavonoids specifically inhibit iodothyronine-deiodinase in rat hepatocytes.

Functionally intact hepatocytes in suspension metabolize iodothyronines (T4, rT3) by 5'-deiodination. These ITH-5H-deiodination reactions are inhibited by flavonoids. The structure-activity relationships are similar to those found for the 5'-D reaction using microsomal membranes as enzyme source. Different effects of flavonoids on the 5'-deiodination reaction of T4 and rT3 point to additional effects, e.g. ITH cellular uptake, transport and binding. Estimation of gluconeogenesis from lactate by biochemically intact hepatocytes allows us to detect "cell toxic" flavonoid effects with higher sensitivity than estimation of viability by trypan blue exclusion. Gluconeogenesis per se is not affected by T4, T3, rT3 or T3 formed by T4-5'-D reaction.