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AFB₁ 대사에서 phloretion의 이중 활성 효과
임대원,이광,고상상,진효연,은상용,최병민,김복량 圓光大學校 醫科學硏究所 2008 圓光醫科學 Vol.23 No.1
Aflatoxm B₁(AFB₁) is a potent hepatocarcinogen in experimental animals and a hazard to human health in several parts of the world. AFB₁ is activated to its ultimate carcinogenic intermediate, AFB₁-8,9-epoxide, by cytochrome P450(CYP) 1A2 and CYP3A4 in human liver and the intermediate is decomposed by several glutathione S-transferase(GST) including GSTA2, GSTM1 and GSTP1. In this study, we investigated the effects of phloretin on the enzyme systems which are involved in the activation and detoxification of AFB₁. The metabolic intermediate of AFB₁ was measured with HPLC. We found that phloretin could strongly inhibit the activities of CYP 3A4 and CYP1A2 in a dose dependent manner. Phloretin induced the antioxidant-response element(ARE)-mediated gene expression, including GSTs. The expressions of GSTA2, T1, M1, and GSTP1 were induced by 10μM phloretin. The decomposition of AFB₁-8,9-epoxide was measured with GSH conjugating activity of the epoxide. The rate was increased to 1.5 fold when HepG2 cells were treated by 10μM phloretin for 12h. In the mean while, the total GST activitives toward CDNB in HepG2 cells were not changed by the treatment with phloretin. The results demonstrate that phloretin has strong chemopreventive effects against AFB₁ toxicity through the inhibition of AFB₁ activation and induction of GSTs.
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