Costa Stefano, Utan Anelì, Speroni Ester, Cervellati Rinaldo, Piva Gianfranco, Prandini Aldo, Guerra Maria Clelia
Department of Pharmacology, University of Bologna, Italy.
J Appl Toxicol. 2007 Mar-Apr;27(2):152-9. doi: 10.1002/jat.1186.
Since oxidative stress plays an important role in the toxicity mechanism of several mycotoxins such as aflatoxin B1 (AFB1), the use of natural or synthetic free radical scavengers could be a potential chemopreventive strategy. Carnosic acid (CA) is the major polyphenolic compound present in rosemary plants and it can also be found in sage leaves. Its free radical scavenging properties were tested with two chemical methods. It was found that it has good free radical scavenging capacity at pH 7.4. This study also found that a 24 h pre-treatment with 10, 20 and 30 microm CA led to a clear, dose-dependent protective effect on cell toxicity, reducing cell death induced by a 24 h exposure with 10 microm AFB1, respectively, by 16% (P < 0.05), 26% (P < 0.01) and 63% (P < 0.001). It was also found that a 24 h pre-treatment with 20 and 30 microm CA achieved a reduction of ROS levels, respectively, of 146% (P < 0.001) and 173% (P < 0.001) in HepG2 cells exposed to 10 microm AFB1 for 8 h. Moreover, in cells pre-incubated with 30 microm CA for 24 h the concentration of 8-OH-deoxyguanine decreased by 57% (P < 0.001) with respect to the cells exposed for 24 h to 10 microm AFB1 alone. The results obtained with the in vitro and chemical studies support the theory that AFB1 induced oxidative stress plays an important role in the cytotoxic mechanism of this mycotoxin. Furthermore these findings suggest a starting point for developing alimentary strategies in order to counteract the damage caused by AFB1 contamination in feed and food.
由于氧化应激在黄曲霉毒素B1(AFB1)等多种霉菌毒素的毒性机制中起着重要作用,因此使用天然或合成的自由基清除剂可能是一种潜在的化学预防策略。肌醇六磷酸(CA)是迷迭香植物中存在的主要多酚化合物,在鼠尾草叶中也能找到。用两种化学方法测试了其自由基清除特性。发现在pH 7.4时它具有良好的自由基清除能力。该研究还发现,用10、20和30微摩尔CA进行24小时预处理对细胞毒性产生了明显的剂量依赖性保护作用,分别将10微摩尔AFB1 24小时暴露诱导的细胞死亡减少了16%(P<0.05)、26%(P<0.01)和63%(P<0.001)。还发现,用20和30微摩尔CA进行24小时预处理后,在暴露于10微摩尔AFB1 8小时的HepG2细胞中,活性氧水平分别降低了146%(P<0.001)和173%(P<0.001)。此外,在预先用30微摩尔CA孵育24小时的细胞中,相对于仅暴露于10微摩尔AFB1 24小时的细胞,8-羟基脱氧鸟苷的浓度降低了57%(P<0.001)。体外和化学研究获得的结果支持了AFB1诱导的氧化应激在这种霉菌毒素的细胞毒性机制中起重要作用的理论。此外,这些发现为制定饮食策略以抵消饲料和食品中AFB1污染造成的损害提供了一个起点。