Department of Zoology, Panjab University, Chandigarh, India.
Mol Biol Rep. 2019 Oct;46(5):5355-5369. doi: 10.1007/s11033-019-04991-5. Epub 2019 Jul 26.
Arsenic is well known genotoxicant which causes the excessive generation of reactive oxygen species (ROS) and inhibition of antioxidant enzyme systems leading to cell damage through the activation of oxidative sensitive signaling pathways. Epigallocatechin gallate (EGCG), the main and active polyphenolic catechin present in green tea, has shown potent antioxidant, free radical scavenging and genoprotective activity in vivo. The present study attempted to investigate antioxidant and geno-protective efficacy of EGCG by regulating arsenic induced oxidative stress in mice. Animals received prophylactic and therapeutic treatments at two different doses (25 and 50 mg/kg b.wt.) of EGCG orally for 15 days and administered arsenic intraperitoneally at dose of 1.5 mg/kg b.wt (1/10th of LD) for 10 days. Arsenic intoxication revealed enhanced ROS production (114%) in lymphocytes; elevated levels of LPO (2-4 fold); reduced levels of hepato-renal antioxidants (approx. 45%) and augmented genomic fragmentation in hepato-renal tissues; increased chromosomal anomalies (78%) and micronucleation (21.93%) in bone marrow cells and comet tailing (25%) in lymphocytes of mice. Both pre and post treatments of EGCG decreased ROS production, restored lipid peroxidation (LPO) and reduced hepato-renal antioxidants levels, reduced the DNA fragmentation, number of chromosomal aberrations (CA), micronucleation (MN), and comet tailing but prophylactic treatment of 50 mg/kg b.wt was the most effective treatment in regulating arsenic induced oxidative stress. The effectiveness of this dose was furthermore validated by calculating the inhibitory index. Thus, results of present work empirically demonstrate free radical scavenging, anti-oxidative and genoprotective efficacy of EGCG against arsenic toxicity.
砷是一种众所周知的遗传毒性物质,它会导致活性氧(ROS)的过度产生,并抑制抗氧化酶系统,从而通过激活氧化敏感的信号通路导致细胞损伤。表没食子儿茶素没食子酸酯(EGCG)是绿茶中主要的、有活性的多酚儿茶素,它在体内表现出强大的抗氧化、自由基清除和遗传保护活性。本研究试图通过调节砷诱导的小鼠氧化应激来研究 EGCG 的抗氧化和遗传保护作用。动物接受了两种不同剂量(25 和 50mg/kg b.wt.)的 EGCG 预防性和治疗性口服治疗,持续 15 天,并腹腔内注射 1.5mg/kg b.wt 的砷(LD 的 1/10),持续 10 天。砷中毒导致淋巴细胞中 ROS 产生增加(114%);LPO 水平升高(2-4 倍);肝肾功能抗氧化剂水平降低(约 45%);肝肾功能组织基因组碎片化增加;骨髓细胞中的染色体异常(78%)和微核形成(21.93%)以及淋巴细胞中的彗星尾化(25%)增加。EGCG 的预治疗和后治疗均降低了 ROS 产生,恢复了脂质过氧化(LPO)并降低了肝肾功能抗氧化剂水平,减少了 DNA 片段化、染色体畸变(CA)、微核形成(MN)和淋巴细胞中的彗星尾化,但 50mg/kg b.wt 的预防治疗是调节砷诱导的氧化应激的最有效治疗方法。通过计算抑制指数进一步验证了这种剂量的有效性。因此,目前的工作结果从经验上证明了 EGCG 对砷毒性的自由基清除、抗氧化和遗传保护作用。