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矢车菊素-3-O-β-吡喃葡萄糖苷,一种天然自由基清除剂,可对抗黄曲霉毒素B1和赭曲霉毒素A在人肝癌细胞系(Hep G2)和人结肠腺癌细胞系(CaCo-2)中诱导的细胞损伤。

Cyanidin-3-O-beta-glucopyranoside, a natural free-radical scavenger against aflatoxin B1- and ochratoxin A-induced cell damage in a human hepatoma cell line (Hep G2) and a human colonic adenocarcinoma cell line (CaCo-2).

作者信息

Guerra M C, Galvano F, Bonsi L, Speroni E, Costa S, Renzulli C, Cervellati R

机构信息

Department of Pharmacology, University of Bologna, 40126 Bologna, Italy.

出版信息

Br J Nutr. 2005 Aug;94(2):211-20. doi: 10.1079/bjn20051425.

Abstract

Recent findings have suggested that oxidative damage might contribute to the cytotoxicity and carcinogenicity of aflatoxin B1 (AFB1). Induction of oxidative stress also plays an important role in the toxicity of another mycotoxin, ochratoxin A (OTA). In the present study, the protective effect of cyanidin-3-O-beta-glucopyranoside (C-3-G; an anthocyanin contained in oranges, blackberries, strawberries and cranberries) against AFB1- and OTA-induced cytotoxicity was investigated in a human hepatoma-derived cell line (Hep G2) and a human colonic adenocarcinoma cell line (CaCo-2). The ability of C-3-G to reduce the production of reactive oxygen species (ROS), the inhibition of protein and DNA synthesis and the apoptosis caused by the two mycotoxins was also investigated in both cell lines. Our experiments proved the significant cytoprotective effect of C-3-G in vitro against OTA- and AFB1-induced cell damage. In particular, 24 h of pretreatment with 50 microm-C-3-G inhibited the cytotoxicity of 10 microm-AFB1 (by 35 %) and of 10 microm-OTA (by 25 %) in Hep G2 cells (P < 0.001) and of 10 microm-AFB1 (by 10 %, P < 0.01) and of 10 microm-OTA (by 14 %, P < 0.05) in CaCo-2 cells. Moreover, 50 microm-C-3-G attenuated ROS production induced by the two toxins in both cell lines (P < 0.05). Inhibition of DNA and protein synthesis induced by the mycotoxins was counteracted by pretreatment with the antioxidant at 50 microm. Similarly, apoptotic cell death was prevented as demonstrated by a reduction of DNA fragmentation and inhibition of caspase-3 activation. The in vitro free-radical scavenging capacity of the anthocyanin was tested with the Briggs-Rauscher oscillating reaction. This system works at pH approximately 2. The results showed good scavenging power, in accordance with the observed inhibition of ROS production.

摘要

最近的研究结果表明,氧化损伤可能导致黄曲霉毒素B1(AFB1)的细胞毒性和致癌性。氧化应激的诱导在另一种霉菌毒素赭曲霉毒素A(OTA)的毒性中也起重要作用。在本研究中,研究了花青素-3-O-β-葡萄糖苷(C-3-G,一种存在于橙子、黑莓、草莓和蔓越莓中的花青素)对人肝癌细胞系(Hep G2)和人结肠腺癌细胞系(CaCo-2)中AFB1和OTA诱导的细胞毒性的保护作用。还研究了C-3-G在两种细胞系中减少活性氧(ROS)产生、抑制蛋白质和DNA合成以及由这两种霉菌毒素引起的细胞凋亡的能力。我们的实验证明了C-3-G在体外对OTA和AFB1诱导的细胞损伤具有显著的细胞保护作用。特别是,用50μM C-3-G预处理24小时可抑制Hep G2细胞中10μM AFB1(35%)和10μM OTA(25%)的细胞毒性(P<0.001),以及CaCo-2细胞中10μM AFB1(10%,P<0.01)和10μM OTA(14%,P<0.05)的细胞毒性。此外,50μM C-3-G可减弱两种毒素在两种细胞系中诱导的ROS产生(P<0.05)。用抗氧化剂50μM预处理可抵消霉菌毒素诱导的DNA和蛋白质合成的抑制。同样,通过减少DNA片段化和抑制caspase-3激活证明可防止凋亡细胞死亡。用Briggs-Rauscher振荡反应测试了花青素的体外自由基清除能力。该系统在pH约为2的条件下工作。结果显示出良好的清除能力,这与观察到的ROS产生的抑制一致。

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