Analyses of protective effects of soy-derived isoflavone against acetaminophen-induced liver injury

我们发现，染料木素，大豆植物雌激素，减少APAP诱导的细胞毒性的两个培养的肝细胞系; HepG 2（人肝细胞癌细胞系）和NCTC克隆1469（小鼠非实质肝细胞）。当这些细胞系用5 mM APAP处理时，48 h时细胞活力分别降低至21.0%和8.6%。而10 μM染料木黄酮可使细胞活力分别恢复到66.1%和52.8%。活性氧（ROS）的生产水平的分析表明，染料木素减少APAP在两种细胞系中产生的ROS。综上所述，这些结果表明，染料木黄酮可能通过抗氧化应激活性对APAP诱导的肝毒性具有保护作用。另一方面，我们观察到染料木黄酮与N-乙酰-L-半胱氨酸（NAC）联合对APAP诱导的小鼠急性肝损伤具有保护作用。由于染料木黄酮是一种常见的食物因子，它应该是一个很有前途的化学保护剂，对APAP诱导的肝损伤。在未来，我们正计划建立一个改进的治疗使用染料木黄酮的APAP诱导的肝损伤。

We found that genistein, a soybean phytoestrogen, reduced APAP-induced cytotoxicity of two cultured liver cell lines; HepG2 (human hepatocellular carcinoma cell line) and NCTC Clone 1469 (a mouse non-parenchymal hepatocyte). When these cell lines were treated with 5 mM APAP, the cell viabilities were decreased to 21.0% and 8.6% at 48 hr, respectively. However, 10 μM genistein restored the both cell viabilities up to 66.1% and 52.8%, respectively. Analyses of reactive oxygen species (ROS) production level revealed that genistein reduced ROS produced by APAP in both cell lines. Taken together, these findings indicated that genistein might have protective effects against APAP-induced hepatotoxicity via anti-oxidative stress activities. On the other hand, we observed that genistein showed protective effects on APAP-induced acute mouse liver injury in combination with N-acetyl-L-cysteine (NAC). Because genistein is a common food factor, it should be a promising protective chemical agent against APAP-induced liver injury. In the future, we are planning to establish the improved therapeutic use of genistein for APAP-induced liver injury.