Triclosan Inhibits the Activity of Expressed Human Sulfotransferases (SULTs) Towards Their Diagnostic Substrates

Abstract

The antibacterial agent, triclosan [5‐chloro‐2(2,4‐dichlorophenoxy)phenol], is added to several consumer products and has been identified in the blood and urine of over 75% of the US population. Triclosan is known to inhibit human hepatic cytosolic SULT activity with several xenobiotic and steroid substrates. In this study we examined the effects of triclosan on isoform‐selective sulfonation of diagnostic substrates of the major SULT isoforms known to be expressed in human liver and intestine. Expressed recombinant SULTs 1A1, 1A3, 1B1, 1E1 and 2A1 were incubated respectively with 4 μM p‐nitrophenol (p‐NP), 10 µM dopamine, 100 µM tri‐iodothyronine (T3), 1 nM estradiol (E2) or 5 µM dehydroepiandrosterone (DHEA), varying amounts of triclosan and buffer (pH 7.4). The sulfonation reaction was started by adding 10 to 20 μM 3′‐phosphoadenosine‐5′‐phosphosulfate.Triclosan inhibited SULTs 1E1, 1B1 and 1A1 activities towards E2, T3 and p‐NP most potently with IC50 values of 0.017, 2.1 and 3.6 µM, respectively. Triclosan was a weaker inhibitor of SULTs 1A3 and 2A1 towards dopamine or DHEA, with respective IC50 values of 31.1 and 431 µM. This work confirms the high potency of triclosan as an inhibitor of estrogen sulfotransferase, and demonstrates inhibitory interactions with other sulfotransferases. Supported in part by R21 ES020545 and seed funds from the University of Florida.