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Arsenic-Induced Hepatic Toxicity and Its Attenuation by Fruit Extract of Emblica officinalis (Amla) in Mice

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Abstract

Arsenic a metalloid and environmental contaminated has been found to be associated with public health problems in the affected areas. It is naturally occurred in groundwater and its accumulation in plant and animals leads to toxicity in several tissues most notably hepatic organ. Arsenic exposures (3 mg/kg body weight/day for 30 days) in mice exhibited increased arsenic and Zn levels in hepatocytes associated with enhanced oxidative stress in hepatocytes while there were no significantly changes were observed in Cu level. An increase in the lipid peroxidation and decrease in the levels of reduced glutathione and activity of superoxide dismutase, catalase, and glutathione peroxidase were observed in arsenic treated mice as compared to controls. Arsenic exposure in mice also caused a significant change in serum biomarkers in the SGOT, SGPT and creatinine as compared to the controls. There were no significant changes in the serum levels of total protein in these mice. Co-administration of arsenic and fruit extract of amla (500 mg/kg body weight/day for 30 days) caused a significant reduction of arsenic transference associated with significantly decreases hepatic arsenic levels and balanced the antioxidant enzyme and levels of serum hepatic enzymes like SGOT and SGPT. The results of the present study clearly demonstrate the antioxidant property of amla that could be responsible for its protective efficacy in arsenic induced hepatic toxicity.

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References:

  1. Brinkel J, Khan MMH, Kraemer A. A systematic review of arsenic exposure and its social and mental health effects with special reference to Bangladesh. Int J Environ Res Public Health. 2009;6:1609–19.

    Article  PubMed  Google Scholar 

  2. Yadav RS, Sankhwar ML, Shukla RK, Chandra R, Pant AB, Islam F, et al. Attenuation of arsenic neurotoxicity by curcumin in rats. Toxicol Appl Pharmacol. 2009;240:367–76.

    Article  CAS  PubMed  Google Scholar 

  3. Ahamed S, Sengutpa MK, Mukherjee A, Hossain A, Das B, Nayak BA, et al. Arsenic ground water contamination and its health effects in the state of Uttar Pradesh (UP) in upper and middle Ganga plain, India: severe danger. Sci Total Environ. 2006;370:310–22.

    Article  CAS  PubMed  Google Scholar 

  4. Kapaj S, Peterson H, Liber K, Bhattacharya P. Human health effects from chronic arsenic poisoning—a review. J Environ Sci Health A. 2006;41:2399–428.

    Article  CAS  Google Scholar 

  5. Klaassen CD. Heavy metals and heavy-metal antagonist. In: Gilman AG, Rall TW, Nies AS, Taylor P, editors. The pharmacological basis of therapeutics. New York: McGraw-Hill; 1996. p. 1592–614.

    Google Scholar 

  6. Aposhian HV, Aposhian MM. Newer developments in arsenic toxicity. J Am Coll Toxicol. 1989;8:1297–305.

    Article  Google Scholar 

  7. WHO, Environmental health criteria 224, arsenic and arsenic compounds. Inter-organization programme for the sound management of chemicals. Geneva 2001.

  8. Liu J, Liu Y, Goyer RA, Achanzar W, Waalkes MP. Metallothionein-I/II null mice are more sensitive than wild-type mice to the hepatotoxic and nephrotoxic effects of chronic oral or injected inorganic arsenicals. Toxicol Sci. 2000;55:460–7.

    Article  CAS  PubMed  Google Scholar 

  9. Markovich D, James KM. Heavy metals mercury, cadmium and chromium inhibit the activity of the mammalian liver and kidney sulfate transporter sat-1. Toxicol Appl Pharmacol. 1999;154:181–7.

    Article  CAS  PubMed  Google Scholar 

  10. Dash DK, Yeligar VC, Nayak SS, Ghosh T, Rajalingam D, Sengupta P, et al. Evaluation of hepatoprotective and antioxidant activity of Ichnocarpus frutescens (Linn.) R. Br. on paracetamol-induced hepatotoxicity in rats. Trop J Pharm Res. 2007;6:755–65.

    Article  Google Scholar 

  11. Ramirez P, Del Razo LM, Gutierrez-Ruiz MC, Gonsebatt ME. Arsenite induces DNA-protein crosslinks and cytokeratin expression in the WRL-68 human hepatic cell line. Carcinogenesis. 2000;21:701–6.

    Article  CAS  PubMed  Google Scholar 

  12. Khan KH. Roles of Emblica officinalis in medicine—a review. Bot Res Int. 2009;2(4):218–28.

    CAS  Google Scholar 

  13. Flora SJS. Arsenic-induced oxidative stress and its reversibility. Free Radical Biol Med. 2011;51:257–81.

    Article  CAS  Google Scholar 

  14. Yadav RS, Sankhwar ML, Shukla RK, Chandravanshi LP, Ansari RW, Shukla PK, et al. Neuroprotective efficacy of curcumin in arsenic induced cholinergic dysfunctions in rats. NeuroToxicology. 2011;32:760–8.

    Article  CAS  PubMed  Google Scholar 

  15. Sharma A, Sharma MK, Kumar M. Modulatory role of emblica officinalis fruit extract against arsenic induced oxidative stress in swiss albino mice. Chemico-Biol interact. 2009;180:20–30.

    Article  CAS  Google Scholar 

  16. Sharma P, Pramod J, Sharma PK, Chaturvedi SK, Kothari LK. Effect of vitamin C administration on serum and aortic lipid profile of guinea pigs. Ind J Med Res. 1988;87:283–9.

    CAS  Google Scholar 

  17. Kothari LK, Sharma P. Aggravation of cholesterol induced hyperlipidaemia by chronic vitamin C deficiency: an experimental study in guinea pigs. Acta Biologica. 1988;39:49–57.

    CAS  PubMed  Google Scholar 

  18. Kothari LK, Pramod J, Sharma P, Chaturvedi SK. Influence of age and vitamin C status on serum cholesterol. Int J Epidemiol. 1988;17:929–30.

    Article  CAS  PubMed  Google Scholar 

  19. Habib-ur-Rehman, Yasin KA, Choudhary MA, Khaliq N, Atta-ur-Rahman, Choudhary MI, Malik S. Studies on the chemical constituents of Phyllanthus emblica. Nat Prod Res. 2007;21:775–81.

    Article  CAS  PubMed  Google Scholar 

  20. Krishnaveni M, Mirunalini S. Therapeutic potential of Phyllanthus emblica (amla): the ayurvedic wonder. J Basic Clin Physiol Pharmacol. 2010;21:93–105.

    CAS  PubMed  Google Scholar 

  21. Esterbauer H, Cheesman KH. Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. Methods Enzymol. 1990;186:407–21.

    Article  CAS  PubMed  Google Scholar 

  22. Ellman GL. Tissue sulfhydryl group. Arch Biochem Biophys. 1959;82:70–7.

    Article  CAS  PubMed  Google Scholar 

  23. Bonaventura J, Schroeder WA, Fang S. Human erythrocyte catalase: an improved method of isolation and a revaluation of reported properties. Arch Biochem Biophys. 1972;150:606–17.

    Article  CAS  PubMed  Google Scholar 

  24. Nishikimi M, Rao NA, Yagi K. The occurrence of superoxide anion in the reaction of reduced phenazine methosulphate and molecular oxygen. Biochem Biophys Res Commun. 1972;46:849–54.

    Article  CAS  PubMed  Google Scholar 

  25. Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem. 1974;249:7130–9.

    CAS  PubMed  Google Scholar 

  26. Flohe L, Gunzler WA. Assay of glutathione peroxidase. Methods Enzymol. 1984;105:114–21.

    Article  CAS  PubMed  Google Scholar 

  27. Santra A, Maiti A, Das S, Lahiri S, Charkaborty SK, Mazumder DN. Hepatic damage caused by chronic arsenic toxicity in experimental animals. Toxicol Clin Toxicol. 2000;38(4):395–405.

    Article  CAS  Google Scholar 

  28. Rossman TG. Mechanism of arsenic carcinogenesis: an integrated approach. Mutat Res. 2003;533:37–65.

    Article  CAS  PubMed  Google Scholar 

  29. Patrick L. Toxic metal and antioxidants: part II. The role of antioxidant in arsenic and cadmium toxicity. Altern Med Rev. 2003;8:106–28.

    PubMed  Google Scholar 

  30. Das S, Santra A, Lahiri S, Guha Mazumder DN. Implication of oxidative stress and hepatic cytokine (TNF-alpha and IL-6) response in the pathogenesis of hepatic collagenesis in chronic arsenic toxicity. Toxicol Appl Pharmacol. 2005;204:18–26.

    Article  CAS  PubMed  Google Scholar 

  31. Mazumder S, Mukherjee S, Mitra A, Karmakar S, Das AS, Mukherjee M, Nanda A, Mitra C. Folic acid or combined of folic acid and vitamin12 prevent short term arsenic trioxide-induced systemic and mitrochondrial dysfunction and DNA damage. Environ Biophys. 2009;860:277–85.

    Google Scholar 

  32. Navarro CM, Montilla PM, Martin A, Jimenez J, Utrilla PM. Free radicals scavenger and anti-hepatotoxic activity of Rosmarinus. Plant Med. 1993;59:312–4.

    Article  Google Scholar 

  33. Green DR, Kroemer G. The pathophysiology of mitochondrial cell death. Science. 2004;305:626–9.

    Article  CAS  PubMed  Google Scholar 

  34. Rehaily AJAI, TAAl Howiriny, Sohaibani MOAI, Rafatullah S. Gastro protective role of (Amla) Emblica-officinalis on in vivo test models in rats. Phytomedicine. 2002;9:515–22.

    Article  Google Scholar 

  35. Flora SJS, Gupta R. Beneficial effect of Centella asiatica aqueous extract against arsenic induced oxidative stress and essential metal status in rats. Phytother Res. 2007;21:980–8.

    Article  CAS  PubMed  Google Scholar 

  36. Sinha M, Manna P, Sil PC. Protective effect of arjunolic acid against arsenic induced oxidative stress in mouse brain. J Biochem Mol Toxicol. 2008;22(1):15–26.

    Article  CAS  PubMed  Google Scholar 

  37. Carter DE, Aposhian HV, Gandolfi AJ. The metabolism of inorganic arsenic oxides. Gallium arsenide and arsine: a toxicochemical review. Toxicol Appl Pharmacol. 2003;193:309–34.

    Article  CAS  PubMed  Google Scholar 

  38. Ngamkitidechakul C, Jaijoy K, Hansakul P, Soonthornchareonnon N, Sireeratawong S. Antitumour effects of Phyllanthus emblica L: induction of cancer cell apoptosis and inhibition of in vivo tumour promotion and in vitro invasion of human cancer cells. Phytother Res. 2010;24:1405–13.

    Article  CAS  PubMed  Google Scholar 

  39. Phromnoi K, Yodkeeree S, Anuchapreeda S, Limtrakul P. Inhibition of MMP-3 activity and invasion of the MDA-MB-231 human invasive breast carcinoma cell line by bioflavonoids. Acta Pharmacol Sin. 2009;30:1169–76.

    Article  CAS  PubMed  Google Scholar 

  40. Ho HH, Chang CS, Ho WC, Liao SY, Wu CH, Wang CJ. Anti-metastasis effects of gallic acid on gastric cancer cells involves inhibition of NF-kappa B activity and downregulation of PI3K/AKT/small GTPase signals. Food Chem Toxicol. 2010;48:2508–16.

    Article  CAS  PubMed  Google Scholar 

  41. Anila L, Vijayalakshmi NR. Antioxidant action of flavonoid from Mangifera indica and Emblica officanalis in hyper cholesterolemic rats. Foods chem. 2003;83:57–569.

    Google Scholar 

  42. Kim HJ, Yokozawa T, Kim HY, Tohda C, Rao TP, Juneja LR. Influence of Amla (Emblica officinalis) on hypercholesterolemia and lipid peroxidation in cholesterol-fed rats. J Nutr Sci Vitaminol. 2005;51:413–8.

    Article  CAS  PubMed  Google Scholar 

  43. Sultana S, Ahmed S, Sharma S, Jahangir T. Emblica officinalis reverses thioacetamide-induced oxidation stress and early promotional events of primary hepatocarcinogenesis. J Pharmacol. 2004;5612:1573–6.

    Article  Google Scholar 

  44. Sharma P, Pramod J, Kothari LK, Ranka R, Sharma S. Hyperlipidaemia in guinea pigs induced by chronic vitamin C deficiency. Ind J Clin Biochem. 1989;4:62–4.

    Article  CAS  Google Scholar 

  45. Sharma P, Pramod J, Sharma PK, Sapra M, Kothari LK. Effect of vitamin C deficiency and excess on liver: a histopathological and biochemical study in guinea pigs fed normal or high cholesterol diet. Ind J Pathol Microbiol. 1990;33(4):307–13.

    CAS  Google Scholar 

  46. Kojo S. Vitamin C: basic metabolism and its function as an index of oxidative stress. Curr Med Chem. 2004;11:1041–64.

    Article  CAS  PubMed  Google Scholar 

  47. Rana T, Bera A, Das K, Pan S, Bandyopadhyay D, Bhattacharyya S, et al. Effect of ascorbic acid on blood oxidative stress in experimental chronic arsenicosis in rodents. Food Chem Toxicol. 2010;48:1027–77.

    Article  Google Scholar 

  48. Kannan GM, Flora SJS. Chronic arsenic poisoning in the rat: treatment with combined administration of succimers and an antioxidant. Ecotoxicol Environ Saf. 2004;58:37–43.

    Article  CAS  PubMed  Google Scholar 

  49. Modi M, Kaul RRK, Kannan GM, Flora SJS. Co-administration of zinc and N-acetylcysteine prevents arsenic induced tissue oxidative stress in male rats. J Trace Elem Med Biol. 2005;20:197–204.

    Article  Google Scholar 

  50. Peraza MA, Ayala-Fierro F, Barber DS, Casarez E, Rael LT. Effects of micronutrients on metal toxicity. Environ Health Perspect. 1998;1:203–16.

    Google Scholar 

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Acknowledgments

Authors are thankful to the Department of Pharmacology, King George’s Medical University Lucknow for providing research facilities and to the Indian Council of Medical Research (ICMR), New Delhi for providing financial assistance as Senior Research Fellow.

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Authors and Affiliations

  1. Department of Pharmacology, King George’s Medical University, Lucknow, 226 003, India

    Manish K. Singh, Suraj S. Yadav & Sanjay Khattri

  2. Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, 342005, India

    Shailendra Dwivedi & Praveen Sharma

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Correspondence to Sanjay Khattri.

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Singh, M.K., Dwivedi, S., Yadav, S.S. et al. Arsenic-Induced Hepatic Toxicity and Its Attenuation by Fruit Extract of Emblica officinalis (Amla) in Mice. Ind J Clin Biochem 29, 29–37 (2014). https://doi.org/10.1007/s12291-013-0353-9

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