Patel Tapan A, Rao Mandava V
a Department of Zoology , Human Genetics Center, School of Sciences, Gujarat University , Ahmedabad , Gujarat , India.
Drug Chem Toxicol. 2015 Oct;38(4):408-14. doi: 10.3109/01480545.2014.975354. Epub 2015 Feb 3.
Various antioxidants play an important role in reducing the reactive oxygen species (ROS) by scavenging them directly or indirectly. Mercury (Hg) is one of the known hazardous genotoxicant, induces the genotoxicity by enhancing the ROS. In the present study, three structurally different bioactive compounds such as melatonin (0.2 mM), curcumin (3.87 µM) and andrographolide (0.4 µM) were evaluated against the genotoxic effect of mercury. All the experiments were conducted using the peripheral blood lymphocytes In Vitro. The cultures were exposed to different doses (2.63 µM; 6.57 µM; 10.52 µM) of mercury salt (HgCl2) for studying various genotoxic indices. All three antioxidant compounds, alone and in combination with high dose of mercury, were added to the cultures with controls. For ascertaining genotoxicity, sister chromatid exchanges (SCEs), cell cycle proliferative index/replicative index (CCPI/RI), average generation time (AGT), population doubling time (PDT), %M1, %M2 and %M3 were assessed and analyzed using suitable statistical analysis. The results revealed a dose dependent increase in SCEs, AGT and PDT, with a concomitant reduction in CCPI values after treatment of mercury. Supplementation of these three antioxidant compounds effectively negated these genotoxic endpoints in treated cultures with improvement in the cell cycle kinetics i.e. CCPI. The antimutagenic activity of these compounds on mercury induced genotoxicity was in the following order: melatonin > curcumin > andrographolide. In conclusion, these compounds have ameliorated mercury induced increase in genotoxic indices due to their excellent antioxidant properties and the combination seems to be effective.
各种抗氧化剂通过直接或间接清除活性氧(ROS)在减少ROS方面发挥着重要作用。汞(Hg)是一种已知的有害基因毒性剂,通过增强ROS诱导基因毒性。在本研究中,评估了三种结构不同的生物活性化合物,即褪黑素(0.2 mM)、姜黄素(3.87 μM)和穿心莲内酯(0.4 μM)对汞的基因毒性作用。所有实验均在体外使用外周血淋巴细胞进行。将培养物暴露于不同剂量(2.63 μM;6.57 μM;10.52 μM)的汞盐(HgCl2)中,以研究各种基因毒性指标。将所有三种抗氧化化合物单独以及与高剂量汞联合添加到有对照的培养物中。为了确定基因毒性,使用合适的统计分析评估并分析了姐妹染色单体交换(SCEs)、细胞周期增殖指数/复制指数(CCPI/RI)、平均世代时间(AGT)、群体倍增时间(PDT)、%M1、%M2和%M3。结果显示,汞处理后,SCEs、AGT和PDT呈剂量依赖性增加,同时CCPI值降低。补充这三种抗氧化化合物有效地消除了处理培养物中的这些基因毒性终点,细胞周期动力学即CCPI得到改善。这些化合物对汞诱导的基因毒性的抗诱变活性顺序如下:褪黑素>姜黄素>穿心莲内酯。总之,这些化合物由于其优异的抗氧化性能改善了汞诱导的基因毒性指标增加,并且联合使用似乎是有效的。