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Effect of butylated hydroxytoluene, curcumin, propyl gallate and thiabendazole on cytochrome P450 forms in cultured human hepatocytes

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Author: Price, R.J. · Scott, M.P. · Giddings, A.M. · Walters, D.G. · Stierum, R.H. · Meredith, C. · Lake, B.G.
Institution: TNO Kwaliteit van Leven
Source:Xenobiotica, 6, 38, 574-586
Identifier: 240810
doi: doi:10.1080/00498250802008615
Keywords: Biology · Physiological Sciences · Butylated hydroxytoluene · Curcumin · CYP induction · Cytochrome P450 (CYP) · Human hepatocytes · Propyl gallate · Thiabendazole · butylcresol · curcumin · cytochrome P450 · cytochrome P450 1A2 · cytochrome P450 2B6 · cytochrome P450 3A4 · ethoxyresorufin deethylase · gallic acid propyl ester · messenger RNA · tiabendazole · adult · aged · article · controlled study · enzyme activity · human · human cell · liver cell · male · Aged · Anthelmintics · Antioxidants · Butylated Hydroxytoluene · Cells, Cultured · Curcumin · Cytochrome P-450 CYP1A1 · Cytochrome P-450 CYP1A2 · Cytochrome P-450 CYP3A · Cytochrome P-450 Enzyme System · Hepatocytes · Humans · Male · Middle Aged · Propyl Gallate · RNA, Messenger · Steroid Hydroxylases · Thiabendazole


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 μM 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 μM TB, with CYP2B6 and CYP 3A4 mRNA levels being induced around 12- and 7-fold, respectively, by 200 μM 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 6β-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. © 2008 Informa UK Ltd.