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

article






Price, R.J.

Scott, M.P.

Giddings, A.M.

Walters, D.G.

Stierum, R.H.

Meredith, C.

Lake, B.G.
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.
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Physiological SciencesButylated hydroxytolueneCurcuminCYP inductionCytochrome P450 (CYP)Human hepatocytesPropyl gallateThiabendazolebutylcresolcurcumincytochrome P450cytochrome P450 1A2cytochrome P450 2B6cytochrome P450 3A4ethoxyresorufin deethylasegallic acid propyl estermessenger RNAtiabendazoleadultagedarticlecontrolled studyenzyme activityhumanhuman cellliver cellmaleAgedAnthelminticsAntioxidantsButylated HydroxytolueneCells, CulturedCurcuminCytochrome P-450 CYP1A1Cytochrome P-450 CYP1A2Cytochrome P-450 CYP3ACytochrome P-450 Enzyme SystemHepatocytesHumansMaleMiddle AgedPropyl GallateRNA, MessengerSteroid HydroxylasesThiabendazole
TNO Identifier
240810
Repository link
https://resolver.tno.nl/uuid:e2f8f189-fc40-408d-b97e-a31082a72738
ISSN
00498254
Source
Xenobiotica, 38(6), pp. 574-586.
Pages
574-586
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