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Depression: 21st Century Solutions + The Dark Side of Wheat

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Abstract Title:

Dual effects of phloretin on aflatoxin B1 metabolism: activation and detoxification of aflatoxin B1.

Abstract Source:

Biofactors. 2012 Jan-Feb;38(1):34-43. Epub 2012 Jan 18. PMID: 22253071

Abstract Author(s):

Shang Shang Gao, Xiao Yan Chen, Ri Zhe Zhu, Byung-Min Choi, Sun Jun Kim, Bok-Ryang Kim

Article Affiliation:

Shang Shang Gao

Abstract:

Typically, chemopreventive agents involve either induction of phase II detoxifying enzymes and/or inhibition of cytochrome P450 enzymes (CYPs) that are required for the activation of procarcinogens. In this study, we investigated the protective effects of phloretin against aflatoxin B1 (AFB1) activation to the ultimate carcinogenic intermediate, AFB(1)-8, 9-epoxide (AFBO), and its subsequent detoxification. Phloretin markedly inhibited formation of the epoxide with human liver microsomes in a dose-dependent manner. Phloretin also inhibited the activities of nifedipine oxidation and ethoxyresorufin O-deethylase (EROD) in human liver microsomes. These data show that phloretin strongly inhibits CYP1A2 and CYP3A4 activities, which are involved in the activation of AFB1. Phloretin increased glutathione S-transferase (GST) activity of alpha mouse liver 12 (AML 12) cells in a dose-dependent manner. GST activity toward AFBO in cell lysates treated with 20μM phloretin was 23-fold that of untreated control cell lysates. The expression of GSTA3, GSTA4, GSTM1, GSTP1 and GSTT1 was induced by phloretin in a dose-dependent manner in AML 12 cells. GSTP1, GSTM1, and GSTT1 were able to significantly increase the conjugation of AFBO with glutathione. Concurrently, induction of the GST isozyme genes was partially associated with the Nrf2/ARE pathway. Taken together, the results demonstrate that phloretin has a strong chemopreventive effect against AFB1 through its inhibitory effect on CYP1A2, CYP3A4, and its inductive effect on GST activity.

Study Type : In Vitro Study

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Sayer Ji
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Depression: 21st Century Solutions + The Dark Side of Wheat

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