Effect of butylated hydroxytoluene, curcumin, propyl gallate and thiabendazole on cytochrome P450 forms in cultured human hepatocytes.
1. The objective of this study was to investigate the effects of four food chemicals, namely butylated hydroxytoluene (BHT), curcumin (CC), propyl gallate (PG) and thiabendazole (TB), on cytochrome P450 (CYP) forms in cultured human hepatocytes. 2. Treatment of human hepatocytes for 72 h with 2-200 microM TB produced concentration-dependent increases in CYP1A2, CYP2B6 and CYP3A4 mRNA levels, whereas treatment with BHT increased CYP2B6 and CYP3A4 mRNA levels. CYP1A2, CYP2B6 and CYP3A4 mRNA levels were induced around 48-, 21- and 9-fold, respectively, by 200 microM TB, with CYP2B6 and CYP 3A4 mRNA levels being induced around 12- and 7-fold, respectively, by 200 microM BHT. 3. In contrast, the treatment of human hepatocytes for 72 h with PG and CC had little or no effect on CYP mRNA levels. 4. The treatment of human hepatocytes with TB also induced CYP1A-dependent 7-ethoxyresorufin O-deethylase activity, whereas BHT induced CYP3A-dependent testosterone 6beta-hydroxylase activity. 5. In summary, the results demonstrate that TB is a mixed inducer of CYP forms in human hepatocytes inducing CYP1A, CYP2B and CYP3A forms, whereas BHT is an inducer of CYP2B and CYP3A forms.
LFI Molecular Sciences, Leatherhead, UK.
R J
RJ
Price
M P
MP
Scott
A M
AM
Giddings
D G
DG
Walters
R H
RH
Stierum
C
C
Meredith
B G
BG
Lake
D000368:Aged; D000871:Anthelmintics / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D002084:Butylated Hydroxytoluene / Q000494:pharmacology*; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology*; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics / Q000378:metabolism; D065702:Cytochrome P-450 CYP2B6; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011435:Propyl Gallate / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000378:metabolism; D013827:Thiabendazole / Q000494:pharmacology*
D000871:Anthelmintics; D000975:Antioxidants; D012333:RNA, Messenger; D002084:Butylated Hydroxytoluene; D011435:Propyl Gallate; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; C585599:CYP2B6 protein, human; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D065702:Cytochrome P-450 CYP2B6; D051544:Cytochrome P-450 CYP3A; C022657:steroid hormone 6-beta-hydroxylase; D003474:Curcumin; D013827:Thiabendazole