Protective Role of EGCG Against Malathion Induced Genotoxicity Using Human Lymphocytes

Abstract

Background: Green tea (Camellia sinensis), which is the most common drink across the world after water, has many antioxidant properties. Epigallocatecin-3-gallate (EGCG) is a flavonoid which accounts for 33–50% of green tea solids. It functions as a powerful antioxidant, preventing oxidative damage in healthy cells, with antiangiogenic and antitumor activities and as a modulator of tumor cell response to chemotherapy. Malathion is an organophosphate pesticide which is widely used in agriculture, veterinary and industries. Oxidative stress has been identified as one of malathion’s main molecular mechanisms. The purpose of this study was to evaluate protective role of EGCG against malathion induced genotoxicity using human lymphocyte model. Blood samples from 8 non-smoker healthy volunteers with no history of chemotherapy were collected and divided into six groups: Control, EGCG (50 µM), EGCG (20 µM), Malathion (24 µM), EGCG (50 µM)+Malathion (24 µM) and EGCG (20 µM)+Malathion (24 µM). For genotoxicity assay, we employed micronuclei test. For antioxidant capacity evaluation, GSH content and MDA levels were measured. Malathion showed significant genotoxic damage compared to the intact lymphocytes, however, treatment with EGCG at both concentrations were reduced the genotoxic effect of malathion. Malathion induced lipid peroxidation, while pre-treatment with EGCG at both concentrations, significantly protected the lymphocytes against malathion induced lipid peroxidation. Malathion significantly reduced GSH content, but pre-treatment with EGCG significantly recovered GSH content. Overall this study demonstrated that EGCG (at both concentrations) significantly prevents human lymphocytes against malathion induced genotoxicity and oxidative damage.

Key words

anticancer drugs - toxicology - pharmacogenetics

• References

• 1 Laetz CA, Baldwin DH, Hebert V. et al. Interactive neurobehavioral toxicity of diazinon, malathion, and ethoprop to juvenile coho salmon. Environmental Science & Technology 2013; 47: 2925-2931
• 2 Murakami A, Ashida H, Terao J. Multitargeted cancer prevention by quercetin. Cancer Letters 2008; 269: 315-325
• 3 Pimentel D, Acquay H, Biltonen M. et al. Environmental and economic costs of pesticide use. BioScience 1992; 42: 750-760
• 4 Valavanidis A, Vlahogianni T, Dassenakis M. et al. Molecular biomarkers of oxidative stress in aquatic organisms in relation to toxic environmental pollutants. Ecotoxicology and Environmental Safety 2006; 64: 178-189
• 5 Heikal TM, Ghanem HZ, Soliman MS. Protective effect of green tea extracts against dimethoate induced DNA damage and oxidant/antioxidant status in male rats. Biohealth. Sci Bull 2011; 3: 1-11
• 6 Gee JM, Johnson IT. Polyphenolic compounds: Interactions with the gut and implications for human health. Current Medicinal Chemistry 2001; 8: 1245-1255
• 7 Van der Hooft JJ, Akermi M, Ünlü FY. et al. Structural annotation and elucidation of conjugated phenolic compounds in black, green, and white tea extracts. Journal of Agricultural and Food Chemistry 2012; 60: 8841-88450
• 8 Namita P, Mukesh R. et al. Camellia sinensis (green tea): A review. Global Journal of Pharmacology 2012; 6: 52-59
• 9 Graham HN. Green teacomposition,consumption,and polyphenolchemistry. Preventive Medicine 1992; 21: 334-350
• 10 De Andrade KQ, Moura FA, Dos Santos JM. et al. Oxidative stress and inflammation in hepatic diseases: Therapeutic possibilities of N-acetylcysteine. International Journal of Molecular Sciences 2015; 16: 30269-30308
• 11 Rice-Evans C, Miller N, Paganga G. Antioxidant properties of phenolic compounds. Trends in Plant Science 1997; 2: 152-159
• 12 Nahid Z, Tavakol HS, Abolfazl GK. et al. Protective role of green tea on malathion-induced testicular oxidative damage in rats. Asian Pacific Journal of Reproduction 2016; 5: 42-45
• 13 Lukaszewicz-Hussain A. Role of oxidative stress in organophosphate insecticide toxicity–Short review. Pesticide Biochemistry and Physiology 2010; 98: 145-150
• 14 Tilman D, Cassman KG, Matson PA. et al. Agricultural sustainability and intensive production practices. Nature 2002; 418: 671
• 15 Yao LH, Jiang YM, Shi J. et al. Flavonoids in food and their health benefits. Plant Foods for Human Nutrition 2004; 59: 113-122
• 16 Ortiz-López L, Márquez-Valadez B, Gómez-Sánchez A. et al. Green tea compound epigallo-catechin-3-gallate (EGCG) increases neuronal survival in adult hippocampal neurogenesis in vivo and in vitro. Neuroscience 2016; 322: 208-220
• 17 Zhang H, Tsao R. Dietary polyphenols, oxidative stress and antioxidant and anti-inflammatory effects. Current Opinion in Food Science 2016; 8: 33-42
• 18 Titenko-Holland N, Windham G, Kolachana P. et al. Genotoxicity of malathion in human lymphocytes assessed using the micronucleus assay in vitro and in vivo: A study of malathion-exposed workers. Mutation Research/Genetic Toxicology and Environmental Mutagenesis 1997; 388: 85-95
• 19 Moore PD, Yedjou CG, Tchounwou PB. Malathion-induced oxidative stress, cytotoxicity, and genotoxicity in human liver carcinoma (HepG2) cells. Environmental Toxicology 2010; 25: 221-226
• 20 Gupta J, Siddique YH, Beg T. et al. A review on the beneficial effects of tea polyphenols on human health. International Journal of Pharmacology 2008; 4: 314-338
• 21 Sepand MR, Ghahremani MH, Razavi-Azarkhiavi K. et al. Ellagic acid confers protection against gentamicin-induced oxidative damage, mitochondrial dysfunction and apoptosis-related nephrotoxicity. Journal of Pharmacy and Pharmacology 2016; 68: 1222-1232
• 22 Venkatesan R, Park YU, Yeo EJ. et al. Malathion increases apoptotic cell death by inducing lysosomal membrane permeabilization in N2a neuroblastoma cells: A model for neurodegeneration in Alzheimer’s disease. Cell Death Discovery 2017; 3: 17007
• 23 Hashim EF, Abdella EM. The protective potency of green tea and ginger extracts on the genotoxic effect of malathion insecticide in bone marrow cells of mice (mus musculus). Arab Universities Journal of Agricultural Sciences 2005; 13: 1019-1031
• 24 Yarsan E, Tanyuksel M, Celik S. et al. Effects of aldicarb and malathion on lipid peroxidation. Bulletin of environmental contamination and toxicology 1999; 63: 575-581
• 25 Feng B, Fang Y, Wei SM. Effect and mechanism of epigallocatechin-3-gallate (EGCG). Against the hydrogen peroxide-induced oxidative damage in human dermal fibroblasts. Journal of Cosmetic Science 2013; 64: 35-44