Common food additives are potent inhibitors of human liver 17 alpha-ethinyloestradiol and dopamine sulphotransferases.
Interactions between dietary xenobiotics, drugs and biologically active endogenous compounds are a potential source of idiosyncratic adverse pathology. We have examined the inhibition of the sulphation of a number of xenobiotics and endobiotics in human liver cytosol by 15 food additives and constituents. Sulphation of dehydroepiandrosterone was resistant to inhibition by all compounds tested; however, dopamine sulphotransferase (ST) activity was inhibited strongly by (+/-)-catechin, (+)-catechin, octyl gallate, tartrazine and vanillin. Sulphation of the xenobiotic steroid 17 alpha-ethinyloestradiol (EE2) was inhibited by vanillin, erythrosin B and octyl gallate. Of these compounds, only vanillin was found to be sulphated to a significant extent by both human liver and platelets, and vanillin was determined to be a substrate for the monoamine-sulphating isoenzyme of phenolsulphotransferase. Vanillin was found to inhibit 50% of liver EE2 ST activity (IC50) at a concentration of approximately 1.3 microM and the mode of inhibition was non-competitive. The implications of these results for the adverse side effects associated with food additives and oral contraceptives are discussed.
Bamforth
K J
KJ
Department of Biochemical Medicine, University of Dundee, Ninewells Hospital and Medical School, U.K.
Jones
A L
AL
Roberts
R C
RC
Coughtrie
M W
MW
D015239:Arylsulfotransferase / Q000037:antagonists & inhibitors*; D001547:Benzaldehydes / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D004923:Erythrosine / Q000494:pharmacology; D004997:Ethinyl Estradiol / Q000009:adverse effects / Q000378:metabolism*; D005503:Food Additives / Q000494:pharmacology*; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D015238:Sulfotransferases / Q000037:antagonists & inhibitors*
D001547:Benzaldehydes; D005503:Food Additives; C016627:octyl gallate; D004997:Ethinyl Estradiol; D005707:Gallic Acid; C100058:vanillin; D015238:Sulfotransferases; C084556:ethinylestradiol-17 alpha sulfotransferase; D015239:Arylsulfotransferase; D004923:Erythrosine