Skip to main content

Advertisement

Log in

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

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Roy JS, Chatterjee D, Das N, Giri AK (2018) Substantial evidence indicate that arsenic is a genotoxic carcinogen: a review. Toxicol Res 34:311–324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Parkash C, Kumar V (2016) Chronic arsenic exposure-induced oxidative stress is mediated by decreased mitochondrial biogenesis in rat liver. Biol Trace Elem Res 173:87–95

    Article  Google Scholar 

  3. Brinkel J, Khan MH, Kraemer A (2009) A systematic review of arsenic exposure and its social and mental health effects with special reference to Bangladesh. Int J Environ Res Public Health 6:1609–1619

    Article  PubMed  PubMed Central  Google Scholar 

  4. Argos M, Kalra T, Rathouz PJ, Chen Y, Pierce B, Parvez F, Islam T, Ahmed A, Rakibuz-Zaman M, Hasan R, Sarwar G, Slavkovich V, van Geen A, Graziano J, Ahsan H (2010) Arsenic exposure from drinking water, and all-cause and chronic-disease mortalities in Bangladesh (HEALS): a prospective cohort study. Lancet 376:252–258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Cohen SM, Arnold LL, Beck BD, Lewis AS, Eldan M (2013) Evaluation of the carcinogenicity of inorganic arsenic. Crit Rev Toxicol 43:711–752

    Article  CAS  PubMed  Google Scholar 

  6. Mahata J, Basu A, Ghoshal S, Sarkar JN, Roy AK, Poddar G, Nandy AK, Banerjee A, Ray K, Natarajan AT, Nilsson R, Giri AK (2003) Chromosomal aberrations and sister chromatid exchanges in individuals exposed to arsenic through drinking water in West Bengal, India. Mutat Res 534:133–143

    Article  CAS  PubMed  Google Scholar 

  7. Hei TK, Liu SX, Waldren C (1998) Mutagenicity of arsenic in mammalian cells: role of reactive oxygen species. Proc Natl Acad Sci USA 95:8103–8107

    Article  CAS  PubMed  Google Scholar 

  8. Faita F, Cori L, Bianchi F, Andreassi MG (2013) Arsenic-induced genotoxicity and genetic susceptibility to arsenic-related pathologies. Int J Environ Res Public Health 10:1527–1546

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Mo J, Xia Y, Wade TJ, Schmitt M, Le XC, Dang R, Mumford JL (2006) Chronic arsenic exposure and oxidative stress: OGG1 expression and arsenic exposure, nail selenium and skin hyperkeratosis in Inner Mongolia. Environ Health Perspect 114:835–841

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hossain MB, Vahter M, Concha G, Broberg K (2012) Environmental arsenic exposure and DNA methylation of the tumor suppressor gene p16 and the DNA repair gene MLH1: effect of arsenic metabolism and genotype. Metallomics 4:1167–1175

    Article  CAS  PubMed  Google Scholar 

  11. Sun HJ, Rathinasabapathi B, Wu B, Luo J, Pu LP, Ma LQ (2014) Arsenic and selenium toxicity and their interactive effects in humans. Environ Int 69:148–158

    Article  CAS  PubMed  Google Scholar 

  12. Johnson JJ, Bailey HH, Mukhtar H (2010) Green tea polyphenols for prostate cancer chemoprevention: a translational perspective. Phytomedicine 17:3–13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Park SY, Jeong YJ, Kim SH, Jung JY, Kim WJ (2013) Epigallocatechin gallate protects against nitric oxide-induced apoptosis via scavenging ROS and modulating the Bcl-2 family in human dental pulp cells. J Toxicol Sci 38:371–378

    Article  CAS  PubMed  Google Scholar 

  14. Garcia-Rodriguez Mdel C, Montano-Rodriguez AR, Altamirano-Lozano MA (2016) Modulation of hexavalent chromium-induced genotoxic damage in peripheral blood of mice by epigallocatechin-3-gallate (EGCG) and its relationship to the apoptotic activity. J Toxicol Environ Health 79:28–38

    Article  Google Scholar 

  15. Yang WS, Moon SY, Lee MJ, Park SK (2016) Epigallocatechin-3-gallate attenuates the effects of TNF-α in vascular endothelial cells by causing ectodomain shedding of TNF receptor 1. Cell Physiol Biochem 38:963–974

    Google Scholar 

  16. Chen J, Du L, Li J, Song H (2016) Epigallocatechin-3-gallate attenuates cadmium-induced chronic renal injury and fibrosis. Food Chem Toxicol 96:70–78

    Article  CAS  PubMed  Google Scholar 

  17. Cabrera C, Artacho R, Gimenez R (2006) Beneficial effects of green tea-a review. J Am Col Nutr 25:79–99

    Article  CAS  Google Scholar 

  18. OECD (2001) OECD guidelines for testing of chemicals 423

  19. Kaushal S, Garg V, Ahsan AU, Sharma VL, Chopra M (2017) Alleviation of arsenic induced lung toxicity by Ocimum sanctum in murine model. Int J Pharm Sci Res 8:4604–4613

    CAS  Google Scholar 

  20. Orsolic N, Sirovina D, Gajski G, Garaj-Vrhovac V, Jazvinscak Jembrek M, Kosalec I (2013) Assessment of DNA damage and lipid peroxidation in diabetic mice: effects of propolis and epigallocatechin gallate (EGCG). Mutat Res 757:36–44

    Article  CAS  PubMed  Google Scholar 

  21. Bartosikova L, Necas J (2018) Epigallocatechin gallate: a review. Vet Med 63:443–467

    Article  Google Scholar 

  22. Turner PV, Brabb T, Pekow C, Vasbinder MA (2011) Administration of substance to animal laboratory animals: routes of administration and factors to consider. J Am Assoc Lab Anim Sci 50:600–613

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Beuge JA, Augst SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–310

    Article  Google Scholar 

  24. Beulter E, Duron O, Kelly BM (1963) Improved method for determination of blood glutathione. J Lab Clin Med 61:882–888

    Google Scholar 

  25. Luck H (1971) Catalase. Methods of enzymatic analysis. Academic Press, New York, pp 885–893

    Google Scholar 

  26. Kono Y (1978) Generation of superoxide radical during autooxidation of hydroxylamine and an assay for superoxide dismutase. Arch Biochem Biophy 86:189–195

    Article  Google Scholar 

  27. Habig WH, Pabst MJ, Jakoby WB (1974) Glutathione-S-transferase. The first enzymatic step in mercapturic acid formation. J Biol Chem 249:7130–7139

    CAS  PubMed  Google Scholar 

  28. Horn HD (1971) Glutathione reductase. Methods of enzymatic analysis. Academic Press, New York, pp 875–881

    Google Scholar 

  29. Sambrook J, Fritsh EF, Maniatis T (1989) A laboratory manual. Molecular cloning, 2nd edn. Cold Spring Harbour Laboratory Press, New York

    Google Scholar 

  30. Das KC (1966) Study of human chromosomes by a direct method from bone marrow. Ind J Pediatr 33:264–266

    Article  CAS  Google Scholar 

  31. Hayashi M, Sofuni JI, Ishidate M (1983) An application of acridine orange fluorescent staining to the micronucleus test. Mutat Res 120:241–247

    Article  CAS  PubMed  Google Scholar 

  32. Singh NP, McCoy MT, Tice RR, Schneider EL (1989) A simple technique for quantification of low levels of DNA damage in individual cells. Exp Cell Res 175:184–191

    Article  Google Scholar 

  33. Madrigal-Bujaidar E, Barriga SD, Cassani M, Marquez P, Revuelta P (1998) In vivo and in vitro antigenotoxic effect of nordihydroguaiaretic acid against SCEs induced by methyl methanesulfonate. Mutat Res 419:163–168

    Article  CAS  PubMed  Google Scholar 

  34. Kitchin KT, Conolly R (2010) Arsenic-induced carcinogenesis-oxidative stress as a possible mode of action and future research needs for more biologically based risk assessment. Chem Res Toxicol 23:327–335

    Article  CAS  PubMed  Google Scholar 

  35. Pierce BL, Kibriya MG, Jasmine F, Argos M, Roy S, Paul-Brutus R, Rahaman R, Rakibuz-Zaman M, Parvez F, Ahmed A, Quasem I, Hore SK, Alam S, Islam T, Slavkovich V, Gamble MV, Yunus M, Rahman M, Baron JA, Graziano JH, Ahsan H (2012) Genome-wide association study identifies chromosome 10q24 32 variants associated with arsenic metabolism and toxicity phenotypes in Bangladesh. PLoS Genet 8:1002522

    Article  Google Scholar 

  36. Maheshwari N, Khan FH, Mahmood R (2018) 3,4-Dihydroxybenzaldehyde lowers ROS generation and protects human red blood cells from arsenic (III) induced oxidative damage. Environ Toxicol 33:861–875

    Article  CAS  Google Scholar 

  37. Dutta S, Saha S, Mahalanoish S, Sadhukhan P, Sil PC (2018) Melatonin attenuates arsenic induced nephropathy via regulation of oxidative stress and inflammatory signalling cascade in mice. Food Chem Toxicol 118:303–316

    Article  CAS  PubMed  Google Scholar 

  38. Kenyon EM, Hughes MF, Adair BM, Highfill JH, Crecelius EA, Clewell HJ, Yager JW (2008) Tissue distribution and urinary excretion of inorganic arsenic and its methylated metabolites in C57BL6 mice following subchronic exposure to arsenate in drinking water. Toxicol Appl Pharmacol 232:448–455

    Article  CAS  PubMed  Google Scholar 

  39. Dkhil MA, Al-Khalifa MS, Al-Quraishy S, Zrieq R, Abdel Moneim AE (2016) Indigofera oblongifolia mitigates lead-acetate induced kidney damage and apoptosis in a rat model. Drug Des Dev Ther 10:1847–1856

    Google Scholar 

  40. Kharroubi W, Dhibi M, Mekni M, Haouas Z, Chreif I, Neffati F, Hammami M, Sakly R (2014) Sodium arsenate induced changes in fatty acids profiles and oxidative damage in kidney of rats. Environ Sci Pollut Res Int 21:12040–12049

    Article  CAS  PubMed  Google Scholar 

  41. Dua TK, Dewanjee S, Feo VD (2015) Ameliorative effect of water spinach, Ipomea aquatica (Convolvulaceae), against experimentally induced arsenic toxicity. J Transl Med 13:81–98

    Article  PubMed  PubMed Central  Google Scholar 

  42. Laborde E (2010) Glutathione transferases as mediators of signaling pathways involvedin cell proliferation and cell death. Cell Death Differ 17:1373–1380

    Article  CAS  PubMed  Google Scholar 

  43. Muthumani M, Miltonprabu S (2015) Ameliorative efficacy of tetrahydrocurcumin against arsenic induced oxidative damage, dyslipidemia and hepatic mitochondrial toxicity in rats. Chem Biol Interact 235:95–105

    Article  CAS  PubMed  Google Scholar 

  44. Al-Brakati AY, Kassab RB, Lokman MS, Elmahallawy EK, Amin HK, Abdel Moneim AE (2018) Role of thymoquinone and ebselen in the prevention of sodium arsenite induced nephrotoxicity in female rats. Hum Exp Toxicol 38:482–493

    Article  PubMed  Google Scholar 

  45. Mehrzadi S, Fatemi I, Malayeri AR, Khodadadi A, Mohammadi F, Mansouri E, Rashno M, Goudarzi M (2018) Ellagic acid mitigates sodium arsenite renal and hepatic toxicity in male Wistar rats. Pharm Rep 70:712–719

    Article  CAS  Google Scholar 

  46. Salazar AM, Miller HL, McNeely SC, Sordo M, Ostrosky-Wegman P, States JC (2010) Suppression of p53 and p21 reduces arsenite-induced aneuploidy. Chem Res Toxicol 23:357–364

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Cooke MS, Evans MD, Dizdaroglu M, Lunec J (2003) Oxidative DNA damage: mechanisms, mutation and disease. FASEB J 17:1195–1214

    Article  CAS  PubMed  Google Scholar 

  48. Chopra M, Sobti RC, Sharma VL (2013) Cadmium administration mediated renal toxicity and plausible correlative chromosomal aberrations in mice. Int J Pharmacol Toxicol Sci 3:19–31

    CAS  Google Scholar 

  49. Sankar P, Telang AG, Ramya K, Vijayakaran K, Kesavan M, Sarkar SN (2014) Protective action of curcumin and nano-curcumin against arsenic induced genotoxicity in rats in vivo. Mol Biol Rep 41:7413–7422

    Article  CAS  PubMed  Google Scholar 

  50. Odunola OA, Akinwumi KA, Ibegbu DM (2011) The influence of garlic spondias mombin on sodium arsenite induced clastogenicity hepatotoxicity in rats. Pacific J Sci Technol 12:401–409

    Google Scholar 

  51. Tian D, Ma H, Feng Z, Xia Y, Le XC, Ni Z, Allen J, Collins B, Schreinemachers D, Mumford JL (2001) Analyses of micronuclei in exfoliated epithelial cells from individuals chronically exposed to arsenic via drinking water in Inner Mongolia, China. J Toxicol Environ Health 64:473–484

    Article  CAS  Google Scholar 

  52. Titenko-Holland N, Moore LE (1994) Measurement and characterization of micronuclei in exfoliated human cells by fluorescence in situ hybridization with a centromeric probe. Mutat Res 312:39–59

    Article  CAS  PubMed  Google Scholar 

  53. Basu A, Mahata J, Roy AK, Sarkar JN, Poddar G, Nandy AK, Sarkar PK, Dutta PK, Banerjee A, Das M, Ray K, Roychaudhury S, Natarajan AT, Nilsson R, Giri AK (2002) Enhanced frequency of micronuclei in individuals exposed to arsenic through drinking water in West Bengal, India. Mutat Res 516:29–40

    Article  CAS  PubMed  Google Scholar 

  54. Ochi T, Suzuki T, Barrett JC, Tsutsui T (2004) A trivalent dimethylarsenic compound, dimethylarsine oxide, induces cellular transformation, aneuploidy, centrosome abnormality and multipolar spindle formation in Syrian hamster embryo cells. Toxicology 203:n155–n163

    Article  Google Scholar 

  55. Gebel TW (2001) Genotoxicity of arsenical compounds. Int J Hyg Environ Health 203:249–262

    Article  CAS  PubMed  Google Scholar 

  56. Balakumar BS, Ramanathan K, Kumaresan S, Suresh R (2010) DNA damage by sodium arsenite in experimental rats: ameliorative effects of antioxidant vitamins C, E. Indian J Sci Technol 3:322–327

    CAS  Google Scholar 

  57. Sun T, Liu Z, Qi Z, Huang YP, Gao XQ, Zhang YY (2016) Epigallocatechin-3-gallate (EGCG) attenuates arsenic-induced cardiotoxicity in rats. Food Chem Toxicol 93:102e110

    Article  Google Scholar 

  58. Miltonprabu S, Thangapandiya S (2015) Epigallocatechin gallate potentially attenuates fluoride induced oxidative stress mediated cardiotoxicity and dyslipidemia in rats. J Trace Elem Med Biol 29:321–335

    Article  CAS  PubMed  Google Scholar 

  59. Zhong Y, Shahidi F (2011) Lipophilized epigallocatechin gallate (EGCG) derivatives as a novel antioxidants. J Agric Food Chem 59:6526–6533

    Article  CAS  PubMed  Google Scholar 

  60. Thangapandiyan S, Miltonprabu S (2013) Epigallocatechin gallate effectively ameliorates fluoride-induced oxidative stress and DNA damage in the liver of rats. Can J Physiol Pharmacol 91:528–537

    Article  CAS  PubMed  Google Scholar 

  61. Othman AI, Elkomy MM, El-Missiry MA, Dardor M (2017) Epigallocatechin-3-gallate prevents cardiac apoptosis by modulating the intrinsic apoptotic pathway in isoproterenol-induced myocardial infarction. Eur J Pharmacol 794:27–36

    Article  CAS  PubMed  Google Scholar 

  62. Johnson MK, Loo G (2000) Effects of epigallocatechin gallate and quercetin on oxidative damage to cellular DNA. Mutat Res 459:211–218

    Article  CAS  PubMed  Google Scholar 

  63. Abib RT, Peres KC, Barbosa AM, Peres TV, Bernardes A, Zimmermann LM, Quincozes-Santos A, Fiedler HD, Leal RB, Farina M, Gottfried C (2011) Epigallocatechin-3-gallate protects rat brain mitochondria against cadmium-induced damage. Food Chem Toxicol 49:2618–2623

    Article  CAS  PubMed  Google Scholar 

  64. Thangapandiyan S, Miltonprabu S (2014) Epigallocatechin gallate supplementation protects against renal injury induced by fluoride intoxication in rats: Role of Nrf2/Ho-1 signaling. Toxicol Rep 1:12–30

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Devika PT, Prince SM (2008) (-) Epigalllocatechin-gallate (EGCG) prevents mitochondrial damage in isoproterenol-induced cardiac toxicity in albino Wistar rats: a transmission electron microscopic and in vitro study. Pharm Res 57:351–357

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors are thankful to University Grant Commission-Rajiv Gandhi National Fellowship (F1-17.1/2012-13-RGNF-2012-13-SC-HIM-22387, dated 28-02-2013), University Grant Commission-Centre for Advanced Studies (F.4-28/2015/CAS-II (SAP-II, dated 20-07-2013) and Department of Science and Technology-PURSE for providing financial support to conduct this experimental work.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mani Chopra.

Ethics declarations

Conflict of interest

The authors declare that there is no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kaushal, S., Ahsan, A.U., Sharma, V.L. et al. Epigallocatechin gallate attenuates arsenic induced genotoxicity via regulation of oxidative stress in balb/C mice. Mol Biol Rep 46, 5355–5369 (2019). https://doi.org/10.1007/s11033-019-04991-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-019-04991-5

Keywords

Navigation