Effects of tea polyphenols and flavonoids on liver microsomal glucuronidation of estradiol and estrone.
Administration of 0.5 or 1% lyophilized green tea (5 or 10 mg tea solids per ml, respectively) as the sole source of drinking fluid to female Long-Evans rats for 18 days stimulated liver microsomal glucuronidation of estrone, estradiol and 4-nitrophenol by 30-37%, 15-27% and 26-60%, respectively. Oral administration of 0.5% lyophilized green tea to female CD-1 mice for 18 days stimulated liver microsomal glucuronidation of estrone, estradiol and 4-nitrophenol by 33-37%, 12-22% and 172-191%, respectively. The in vitro addition of a green tea polyphenol mixture, a black tea polyphenol mixture or (-)-epigallocatechin gallate inhibited rat liver microsomal glucuronidation of estrone and estradiol in a concentration-dependent manner and their IC50 values for inhibition of estrogen metabolism were approximately 12.5, 50 and 10 microg/ml, respectively. Enzyme kinetic analysis indicates that the inhibition of estrone glucuronidation by 10 microM (-)-epigallocatechin gallate was competitive while inhibition by 50 microM (-)-epigallocatechin gallate was noncompetitive. Similarly, several flavonoids (naringenin, hesperetin, kaempferol, quercetin, rutin, flavone, alpha-naphthoflavone and beta-naphthoflavone) also inhibited rat liver microsomal glucuronidation of estrone and estradiol to varying degrees. Naringenin and hesperetin displayed the strongest inhibitory effects (IC50 value of approximately 25 microM). These two hydroxylated flavonoids had a competitive mechanism of enzyme inhibition for estrone glucuronidation at a 10 microM inhibitor concentration and a predominantly noncompetitive mechanism of inhibition at a 50 microM inhibitor concentration.
Zhu
B T
BT
Department of Chemical Biology, College of Pharmacy, Rutgers, The State University of New Jersey, Piscataway 08855, USA.
Taneja
N
N
Loder
D P
DP
Balentine
D A
DA
Conney
A H
AH
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000378:metabolism*; D004970:Estrone / Q000378:metabolism; D005260:Female; D044950:Flavanones; D005419:Flavonoids / Q000494:pharmacology*; D005965:Glucuronates / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000378:metabolism; D006569:Hesperidin; D007700:Kinetics; D051379:Mice; D008815:Mice, Inbred Strains; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D009596:Nitrophenols / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology*; D011108:Polymers / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013662:Tea / Q000737:chemistry*; D014535:Uridine Diphosphate Glucuronic Acid / Q000378:metabolism
D004791:Enzyme Inhibitors; D044950:Flavanones; D005419:Flavonoids; D005965:Glucuronates; D009596:Nitrophenols; D010636:Phenols; D011108:Polymers; D013662:Tea; D014535:Uridine Diphosphate Glucuronic Acid; D004970:Estrone; D004958:Estradiol; D006569:Hesperidin; D014453:Glucuronosyltransferase; C005273:naringenin; C013015:hesperetin; C024836:4-nitrophenol