Inhibition of rat liver sulfotransferases SULT1A1 and SULT2A1 and glucuronosyltransferase by dietary flavonoids.
1. Dietary flavonoids including kaempferol, quercetin, genistein and daidzein were tested for their ability to alter the conjugation of oestradiol (E(2)) via rat liver sulfotransferases and glucuronosyltransferase. 2. All four flavonoids inhibited the sulfonation of E(2) via phenol sulfotransferase, SULT1A1 with IC(50)s ranging from 0.29 to 4.61 micro M. Sulfonation of dehydroisoandrosterone (DHEA) via hydroxysteroid sulfotransferase, SULT2A1, was inhibited by higher amounts of the flavonoids (IC(50)s ranging from 34 to 116 micro M). 3. All flavonoids inhibited the formation of E(2)-beta-glucuronides (at carbon atoms 3 and 17) with IC(50)s ranging from 43 to 260 micro M. Glucuronidation of 4-methylumbelliferone (4-MU) was inhibited by high amounts of the flavonoids (IC(50)s ranging from 860 to 1550 micro M). 4. Hydrolysis of sulfonated oestrogens via arylsulfatase-c (ARSC) or 4-methylumbelliferone beta-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.
Mesía-Vela
S
S
Laboratory for Cellular and Biochemical Toxicology, Department of Pharmacology and Toxicology, College of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA.
Kauffman
F C
FC
D000818:Animals; D015239:Arylsulfotransferase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000378:metabolism; D004032:Diet; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D019833:Genistein / Q000737:chemistry / Q000494:pharmacology; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors*; D006923:Hymecromone / Q000031:analogs & derivatives / Q000378:metabolism; D020128:Inhibitory Concentration 50; D007529:Isoflavones / Q000737:chemistry / Q000494:pharmacology; D044949:Kaempferols / Q000737:chemistry / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D011794:Quercetin / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D015238:Sulfotransferases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
D004791:Enzyme Inhibitors; D005419:Flavonoids; D007529:Isoflavones; D044949:Kaempferols; D011994:Recombinant Proteins; D006923:Hymecromone; D003687:Dehydroepiandrosterone; C004742:daidzein; D011794:Quercetin; D019833:Genistein; D014453:Glucuronosyltransferase; D015238:Sulfotransferases; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human; C028152:alcohol sulfotransferase