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

我们发现，大豆植物雌激素金雀异黄素能降低APAP诱导的两种肝细胞系：人肝癌细胞系HepG2和小鼠非实质肝细胞系NCTC Clone 1469的细胞毒作用。5 mM APAP作用48h后，细胞存活率分别降至21.0%和8.6%。而10μM染料木素使两种细胞的存活率分别恢复到66.1%和52.8%。活性氧(ROS)产生水平的分析表明，染料木素减少了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素可能通过抗氧化应激活性对APAP所致的肝毒性具有保护作用。另一方面，我们观察到染料木素与N-乙酰-L-半胱氨酸(NAC)合用对急性肝损伤有保护作用。由于金雀异黄素是一种常见的食物因子，它应该是一种很有前途的保护APAP诱导的肝损伤的化学制剂。在未来，我们计划建立金雀异黄素对APAP诱导的肝损伤的改进治疗用途。

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.