COMMON FOOD-ADDITIVES ARE POTENT INHIBITORS OF HUMAN LIVER 17-ALPHA-ETHINYLESTRADIOL AND DOPAMINE SULFOTRANSFERASES

Interactions between dietary xenobiotics, drugs and biologically activ e endogenous compounds are a potential source of idiosyncratic adverse pathology. We have examined the inhibition of the sulphation of a num ber of xenobiotics and endobiotics in human liver cytosol by 15 food a dditives and constituents. Sulphation of dehydroepiandrosterone was re sistant to inhibition by all compounds tested; however, dopamine sulph otransferase (ST) activity was inhibited strongly by (+/-)-catechin, ( +)-catechin, octyl gallate, tartrazine and vanillin. Sulphation of the xenobiotic steroid 17alpha-ethinyloestradiol (EE2) was inhibited by v anillin, erythrosin B and octyl gallate. Of these compounds, only vani llin was found to be sulphated to a significant extent by both human l iver and platelets, and vanillin was determined to be a substrate for the monoamine-sulphating isoenzyme of phenolsulphotransferase. Vanilli n was found to inhibit 50% of liver EE2 ST activity (IC50) at a concen tration of approximately 1.3 muM and the mode of inhibition was non-co mpetitive. The implications of these results for the adverse side effe cts associated with food additives and oral contraceptives are discuss ed.