Epigallocatechin gallate attenuates arsenic induced genotoxicity via regulation of oxidative stress in balb/C mice

Mol Biol Rep. 2019 Oct;46(5):5355-5369. doi: 10.1007/s11033-019-04991-5. Epub 2019 Jul 26.

Abstract

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 LD50) 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.

Keywords: Arsenic; Epigallocatechin gallate; Genotoxicity; Oxidative stress.

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Apoptosis / drug effects
  • Arsenic / adverse effects
  • Arsenic / toxicity
  • Arsenic Poisoning / drug therapy*
  • Catechin / analogs & derivatives*
  • Catechin / metabolism
  • Catechin / pharmacology
  • DNA Damage / drug effects
  • Female
  • Mice
  • Mice, Inbred BALB C
  • Mutagenicity Tests / methods
  • Oxidative Stress / drug effects*
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects

Substances

  • Antioxidants
  • Reactive Oxygen Species
  • Catechin
  • epigallocatechin gallate
  • Arsenic