Coffee inhibits the glucuronidation of 1-naphthol in rat syncytiotrophoblast cells

The placenta acts as a barrier that protects the fetus from xenobiotics in the maternal blood. Phase II conjugation reactions in the placenta are considered to play an important role in this protective process by transferring polar hydroxyl groups and thereby imparting water solubility that facilitates the excretion of xenobiotics. Since coffee consumption during pregnancy is reported to affect fetal growth and development, we examined its effects upon the conjugation reactions in the rat syncytiotrophoblast cell line TR-TBT 18d-1. We detected a high level of glucuronidation for 1-naphthol, a model compound, in both a dose- and culture time-dependent manner in the TR-TBT 18d-1 cells. However, no sulfation was detected in any of our analyses. Coffee was found to inhibit the glucuronidation of 1-naphthol with an IC₅₀ of 4.5% (v/v). In contrast however, caffeine, which is a major bioactive constituent of coffee, did not show any inhibition at doses of up to 100 μM. Coffee was also found to inhibit UDP-glucuronosyl transferase (UGT) activity towards 1-naphthol in vitro to a similar extent [IC₅₀ = 1.5% (v/v)] as in intact cells. Moreover, the expression of the UGT 1A6, which is known to mainly catalyze the glucuronidation of 1-naphthol, was not affected by coffee. If coffee inhibits placental glucuronidation during pregnancy, its consumption would increase the fetal plasma concentrations of harmful xenobiotics, potentially affecting normal fetal growth and development.