Hepatic and intestinal cytochrome P450 and conjugase activities in rats treated with black tea theafulvins and theaflavins.
Theaflavins and theafulvins, a fraction of thearubigins, were isolated from aqueous infusions of black tea, and their effects on the hepatic and intestinal cytochrome P450 system, and on the glutathione S-transferase, epoxide hydrolase, glucuronosyl transferase and sulphotransferase enzyme systems were investigated in rats following oral intake for four weeks. Neither theafulvins nor theaflavins influenced cytochrome P450 activity in the liver as exemplified by the O-dealkylations of methoxy-, ethoxy- and pentoxyresorufin, the hydroxylations of lauric acid and p-nitrophenol, and the N-demethylation of erythromycin; similarly, hepatic xenobiotic conjugation systems were unaffected. In the intestine, both polyphenolic fractions markedly suppressed the O-deethylation of ethoxyresorufin and this was accompanied by a decrease in the CYP1A1 apoprotein levels. Probing intestinal microsomes with antibodies to CYP2E1 revealed the presence of a single band in the cytochrome P450 region whose intensity was lower in the polyphenol-treated animals. Immunoblot analysis utilising antibodies to CYP3A showed that the treatment with theafulvins and theaflavins reduced the apoprotein levels. A single band in the cytochrome P450 region was evident when the intestinal microsomes were probed with antibodies to CYP4A1 but the level of expression was not affected by the treatment with the black tea polyphenols. Finally, treatment of the rats with theaflavins had no effect on any of the intestinal conjugating enzymes studied, but treatment with theafulvins led to inhibition of glucuronosyl transferase activity.
Catterall
F
F
School of Biomedical and Life Sciences, University of Surrey, Surrey, GU2 7XH, Guildford, UK.
McArdle
N J
NJ
Mitchell
L
L
Papayanni
A
A
Clifford
M N
MN
Ioannides
C
C
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D044946:Biflavonoids; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D015536:Down-Regulation; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D007422:Intestines / Q000187:drug effects / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D010636:Phenols / Q000494:pharmacology*; D059808:Polyphenols; D051381:Rats; D017208:Rats, Wistar; D013662:Tea / Q000737:chemistry*
D000975:Antioxidants; D044946:Biflavonoids; D004791:Enzyme Inhibitors; D010636:Phenols; D059808:Polyphenols; D013662:Tea; C086701:thearubigin; C056068:theaflavin; D002392:Catechin; D003577:Cytochrome P-450 Enzyme System; D014453:Glucuronosyltransferase