EVALUATION OF THE PROTECTIVE EFFECT OF GALLIC ACID AGAINST ARSENIC-INDUCED GENOTOXICITY IN HEPG2 CELL LINE
Objective: Arsenic has cytotoxic as well as mutagenic effect in human health due to its indirect effect on oxidative stress on the cells. We aimed to find out the effect of gallic acid (GA), a well-known natural antioxidant in ameliorating in heavy metal toxicity.
Methods: MTT assay was performed to determine the cytotoxicity of sodium arsenite (NaAsO2) on HepG2 cells with the cytoprotectant GA at varying concentrations for exposure durations of 6 h, 12 h, and 24 h. Similarly, the alkaline version of the comet assay was performed to investigate the genotoxicity and assessment of oxidative stress of the cells using flow cytometry.
Results: Cells treated with NaAsO2 at various doses spanning a broad range of concentrations (5–500 μM) showed a dose- and time-dependent decrease in cellular viability as observed. However, the effect of the proposed protectant, GA showed an increase in cellular viability in a concentration-dependent manner.
Conclusion: We assessed the cytotoxicity and genotoxicity induced by NaAsO2 to provide insight into the role of GA on arsenic-induced toxicity in liver cells and to shed light on its possible ameliorative effect at low concentrations in a time-dependent manner.
2. Hopenhayn-Rich C, Biggs ML, Smith AH, Kalman DA, Moore LE. Methylation study of a population environmentally exposed to arsenic in drinking water. Environ Health Perspect 1996;104:620-8.
3. Ravenscroft P, Brammer H, Richards K. Arsenic Pollution A Global Synthesis. Chichester: John Wiley and Sons; 2011.
4. Chandra S, Saini AK, Gupta AK. Arsenic: A harmful and desecrate compound for the humans. Asian J Pharm Clin Res 2019;12:24-9.
5. Kumar M, Puri A. A review of permissible limits of drinking water. Indian J Occup Environ Med 2012;16:40-4.
6. Ratnaike RN. Acute and chronic arsenic toxicity. Postgrad Med J 2003;79:391-6.
7. Hong YS, Song KH, Chung JY. Health effects of chronic arsenic exposure. J Prev Med Public Health 2014;47:245-52.
8. Saha JC, Dikshit AK, Bandyopadhyay M, Saha KC. A review of arsenic poisoning and its effects on human health. Crit Rev Environ Sci Technol 1999;29:281-313.
9. Khairul I, Wang QQ, Jiang YH, Wang C, Naranmandura H. Metabolism, toxicity and anticancer activities of arsenic compounds. Oncotarget 2017;8:23905-26.
10. Jeon BG, Kumar BM, Kang EJ, Maeng GH, Lee YM, Hah YS, et al. Differential cytotoxic effects of sodium meta-arsenite on human cancer cells, dental papilla stem cells and somatic cells correlate with telomeric properties and gene expression. Anticancer Res 2011;31:4315-28.
11. Kurutas EB. The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: Current state. Nutr J 2016;15:71.
12. Ercal N, Gurer-Orhan H, Aykin-Burns N. Toxic metals and oxidative stress part I: Mechanisms involved in metal-induced oxidative damage. Curr Top Med Chem 2001;1:529-39.
13. Hosseinzadeh A, Houshmand G, Goudarzi M, Sezavar SH, Mehrzadi S, Mansouri E, et al. Ameliorative effect of gallic acid on sodium arsenite-induced spleno-, cardio-and hemato-toxicity in rats. Life Sci 2019;217:91-100.
14. Alley MC, Scudiero DA, Monks A, Hursey ML, Czerwinski MJ, Fine DL, et al. Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay. Cancer Res 1988;48:589-601.
15. Singh NP, McCoy MT, Tice RR, Schneider EL. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 1988;175:184-91.
16. Nandhakumar S, Parasuraman S, Shanmugam MM, Rao KR, Chand P, Bhat BV. Evaluation of DNA damage using single-cell gel electrophoresis (Comet Assay). J Pharmacol Pharmacother 2011;2:107-11.
17. Satish Rao BS, Sreedevi MV, Nageshwar Rao B. Cytoprotective and antigenotoxic potential of mangiferin, a glucosylxanthone against cadmium chloride induced toxicity in HepG2 cells. Food Chem Toxicol 2009;47:592-600.
18. Liu SX, Davidson MM, Tang X, Walker WF, Athar M, Ivanov V, et al. Mitochondrial damage mediates genotoxicity of arsenic in mammalian cells. Cancer Res 2005;65:3236-42.
19. Kim HS, Kim YJ, Seo YR. An overview of carcinogenic heavy metal: Molecular toxicity mechanism and prevention. J Cancer Prev 2015;20:232-40.
20. Carocho M, Ferreira IC. A review on antioxidants, prooxidants and related controversy: Natural and synthetic compounds, screening and analysis methodologies and future perspectives. Food Chem Toxicol 2013;51:15-25.
21. Abiko Y, Shinkai Y, Sumi D, Kumagai Y. Reduction of arsenic-induced cytotoxicity through Nrf2/HO-1 signaling in HepG2 cells. J Toxicol Sci 2010;35:419-23.
22. Watanabe T, Ohta Y, Mizumura A, Kobayashi Y, Hirano S. Analysis of arsenic metabolites in HepG2 and AS3MT-transfected cells. Arch Toxicol 2011;85:577-88.
23. Kobayashi H, Oikawa S, Hirakawa K, Kawanishi S. Metal-mediated oxidative damage to cellular and isolated DNA by gallic acid, a metabolite of antioxidant propyl gallate. Mutat Res 2004;558:111-20.
24. Kong KW, Mat-Junit S, Aminudin N, Hassan FA, Ismail A, Abdul Aziz A. Protective effects of the extracts of Barringtonia racemosa shoots against oxidative damage in HepG2 cells. PeerJ 2016;4:e1628.
25. Pandey KB, Rizvi SI. Plant polyphenols as dietary antioxidants in human health and disease. Oxid Med Cell Longev 2009;2:270-8.
26. Gholamine B, Houshmand G, Hosseinzadeh A, Kalantar M, Mehrzadi S, Goudarzi M. Gallic acid ameliorates sodium arsenite-induced renal and hepatic toxicity in rats. Drug Chem Toxicol 2019;25:1-2.
27. Ambasta SK, Kumari S, Sinha UK. Anticlastogenicity of Tinospora cordifolia stem extract against arsenic genotoxicity in Mus musculus bone marrow erythrocytes using micronucleus assay. Int J Pharm Pharm Sci 2017;9:260-4.
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