Inhibition of rat liver sulfotransferases SULT1A1 and SULT2A1 and glucuronosyltransferase by dietary flavonoids

Abstract

1. Dietary flavonoids including kaempferol, quercetin, genistein and daidzein were tested for their ability to alter the conjugation of oestradiol (E₂) via rat liver sulfotransferases and glucuronosyltransferase.

2. All four flavonoids inhibited the sulfonation of E₂ via phenol sulfotransferase, SULT1A1 with IC₅₀s ranging from 0.29 to 4.61 µM. Sulfonation of dehydroisoandrosterone (DHEA) via hydroxysteroid sulfotransferase, SULT2A1, was inhibited by higher amounts of the flavonoids (IC₅₀s ranging from 34 to 116 µM).

3. All flavonoids inhibited the formation of E₂-β-glucuronides (at carbon atoms 3 and 17) with IC₅₀s ranging from 43 to 260 µM. Glucuronidation of 4-methylumbelliferone (4-MU) was inhibited by high amounts of the flavonoids (IC₅₀s ranging from 860 to 1550 µM).

4. Hydrolysis of sulfonated oestrogens via arylsulfatase-c (ARSC) or 4-methylumbelliferone β-glucuronidate (MUG) were not inhibited by the flavonoids.

5. It is concluded that SULT1A1 but not SULT2A1 or glucuronosyltransferase is highly sensitive to inhibition by dietary flavonoids. The potency of the inhibition for SULT1A1 (quercetin > kaempferol > genistein > daidzein) suggests a dependency on the number and position of hydroxyl radicals in the flavonoid molecule.