Renzulli C, Galvano F, Pierdomenico L, Speroni E, Guerra M C
Department of Pharmacology, University of Bologna, via Irnerio 48, 40126 Bologna, Italy.
J Appl Toxicol. 2004 Jul-Aug;24(4):289-96. doi: 10.1002/jat.982.
Recent findings have suggested that oxidative damage might contribute to the cytotoxicity and carcinogenicity of aflatoxin B(1) (AFB(1)). The induction of oxidative stress also plays an important role in the toxicity of another mycotoxin: ochratoxin A (OTA). In this study, the protective effect of rosmarinic acid (Ros A) against AFB(1) and OTA-induced cytotoxicity was investigated in a human hepatoma-derived cell line (Hep G2). Rosmarinic acid, a natural phenolic compound contained in many Lamiaceae herbs such as Perilla frutescens, sage, basil and mint, inhibits complement-dependent inflammatory processes and may have therapeutic potential. The ability of Ros A to reduce radical oxygen species (ROS) production, protein and DNA synthesis inhibition and apoptosis caused by the two mycotoxins was also investigated. Our experiments proved the significant cytoprotective effect of Ros A in vitro from OTA- and AFB(1)-induced cell damage. In particular, 24-h pretreatment with 50 micro M Ros A inhibited the cytotoxicity of 10 micro M AFB(1) (by 45%) and 10 micro M OTA (by 35%) in Hep G2 cells (P < 0.001). Moreover, Ros A dose dependently attenuated ROS production and DNA and protein synthesis inhibition induced by both of the toxins. Similarly, apoptosis cell death was prevented, as demonstrated by reduction of DNA fragmentation and inhibition of caspase-3 activation (P < 0.001).
最近的研究结果表明,氧化损伤可能导致黄曲霉毒素B(1)(AFB(1))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)的毒性中也起着重要作用。在本研究中,在人肝癌衍生细胞系(Hep G2)中研究了迷迭香酸(Ros A)对AFB(1)和OTA诱导的细胞毒性的保护作用。迷迭香酸是紫苏、鼠尾草、罗勒和薄荷等许多唇形科草药中含有的一种天然酚类化合物,可抑制补体依赖性炎症过程,可能具有治疗潜力。还研究了Ros A减少两种霉菌毒素引起的活性氧(ROS)产生、蛋白质和DNA合成抑制以及细胞凋亡的能力。我们的实验证明了Ros A在体外对OTA和AFB(1)诱导的细胞损伤具有显著的细胞保护作用。特别是,用50μM Ros A进行24小时预处理可抑制Hep G2细胞中10μM AFB(1)(45%)和10μM OTA(35%)的细胞毒性(P<0.001)。此外,Ros A剂量依赖性地减弱了两种毒素诱导的ROS产生以及DNA和蛋白质合成抑制。同样,细胞凋亡性细胞死亡得到了预防,DNA片段化减少和caspase-3激活受到抑制证明了这一点(P<0.001)。