Advertisement

Biological Trace Element Research

, Volume 168, Issue 1, pp 122–132 | Cite as

Arsenic-Induced Antioxidant Depletion, Oxidative DNA Breakage, and Tissue Damages are Prevented by the Combined Action of Folate and Vitamin B12

  • Nirmallya Acharyya
  • Bimal Deb
  • Sandip Chattopadhyay
  • Smarajit Maiti
Article

Abstract

Arsenic is a grade I human carcinogen. It acts by disrupting one-carbon (1C) metabolism and cellular methyl (−CH3) pool. The −CH3 group helps in arsenic disposition and detoxification of the biological systems. Vitamin B12 and folate, the key promoters of 1C metabolism were tested recently (daily 0.07 and 4.0 μg, respectively/100 g b.w. of rat for 28 days) to evaluate their combined efficacy in the protection from mutagenic DNA-breakage and tissue damages. The selected tissues like intestine (first-pass site), liver (major xenobiotic metabolizer) and lung (major arsenic accumulator) were collected from arsenic-ingested (0.6 ppm/same schedule) female rats. The hemo-toxicity and liver and kidney functions were monitored. Our earlier studies on arsenic-exposed humans can correlate carcinogenesis with DNA damage. Here, we demonstrate that the supplementation of physiological/therapeutic dose of vitamin B12 and folate protected the rodents significantly from arsenic-induced DNA damage (DNA fragmentation and comet assay) and hepatic and renal tissue degeneration (histo-architecture, HE staining). The level of arsenic-induced free-radical products (TBARS and conjugated diene) was significantly declined by the restored actions of several antioxidants viz. urate, thiol, catalase, xanthine oxidase, lactoperoxidase, and superoxide dismutase in the tissues of vitamin-supplemented group. The alkaline phosphatase, transaminases, urea and creatinine (hepatic and kidney toxicity marker), and lactate dehydrogenase (tissue degeneration marker) were significantly impaired in the arsenic-fed group. But a significant protection was evident in the vitamin-supplemented group. In conclusion, the combined action of folate and B12 results in the restitution in the 1C metabolic pathway and cellular methyl pool. The cumulative outcome from the enhanced arsenic methylation and antioxidative capacity was protective against arsenic induced mutagenic DNA breakages and tissue damages.

Keywords

Arsenic Antioxidant systems DNA breakage Vitamin B12 Folate 

Notes

Conflict of Interest

The author(s) declared no potential conflicts of interests with respect to the authorship and/or publication of this article.

Source of Funding

Institutional

References

  1. 1.
    NRC (1999) National Research Council: arsenic in the drinking water. National Academy Press, Washington, pp 1–310Google Scholar
  2. 2.
    Zampella G, Neupane KP, De Gioia L, Pecoraro VL (2012) The importance of stereochemically active lone pairs for influencing Pb(II) and As(III) protein binding. Chemistry (Weinheim an der Bergstrasse, Germany) 18:2040–2050Google Scholar
  3. 3.
    Salnikow K, Zhitkovich A (2008) Genetic and epigenetic mechanisms in metal carcinogenesis and cocarcinogenesis: nickel, arsenic, and chromium. Chem Res Toxicol 21:28–44PubMedCentralCrossRefPubMedGoogle Scholar
  4. 4.
    Calatayud M, Devesa V, Velez D (2013) Differential toxicity and gene expression in Caco-2 cells exposed to arsenic species. Toxicol Lett 218:70–80CrossRefPubMedGoogle Scholar
  5. 5.
    Finsterer J, Ohnsorge P (2013) Influence of mitochondrion-toxic agents on the cardiovascular system. Regul Toxicol Pharmacol: RTP 67:434–445CrossRefPubMedGoogle Scholar
  6. 6.
    Liu X, Fan Y, Jiang Y, Xiang J, Wang J, Sun Z, Ren G, Yao S, Chang R, Zhao Y, Qiao Y, Zhou Q (2013) A cohort study on risk factors of lung cancer in Yunnan tin miners. Zhongguo Fei Ai Za Zhi = Chin J Lung Cancer 16:184–190Google Scholar
  7. 7.
    Liu F, Jan KY (2000) DNA damage in arsenite- and cadmium-treated bovine aortic endothelial cells. Free Radic Biol Med 28:55–63CrossRefPubMedGoogle Scholar
  8. 8.
    Lynn S, Gurr JR, Lai HT, Jan KY (2000) NADH oxidase activation is involved in arsenite-induced oxidative DNA damage in human vascular smooth muscle cells. Circ Res 86:514–519CrossRefPubMedGoogle Scholar
  9. 9.
    Glantzounis GK, Tsimoyiannis EC, Kappas AM, Galaris DA (2005) Uric acid and oxidative stress. Curr Pharm Des 11:4145–4151CrossRefPubMedGoogle Scholar
  10. 10.
    Gamble MV, Ahsan H, Liu X, Factor-Litvak P, Ilievski V, Slavkovich V, Parvez F, Graziano JH (2005) Folate and cobalamin deficiencies and hyperhomocysteinemia in Bangladesh. Am J Clin Nutr 81:1372–1377PubMedCentralPubMedGoogle Scholar
  11. 11.
    Gamble MV, Liu X, Ahsan H, Pilsner R, Ilievski V, Slavkovich V, Parvez F, Levy D, Factor-Litvak P, Graziano JH (2005) Folate, homocysteine, and arsenic metabolism in arsenic-exposed individuals in Bangladesh. Environ Health Perspect 113:1683–1688PubMedCentralCrossRefPubMedGoogle Scholar
  12. 12.
    Gamble MV, Liu X, Ahsan H, Pilsner JR, Ilievski V, Slavkovich V, Parvez F, Chen Y, Levy D, Factor-Litvak P, Graziano JH (2006) Folate and arsenic metabolism: a double-blind, placebo-controlled folic acid-supplementation trial in Bangladesh. Am J Clin Nutr 84:1093–1101PubMedCentralPubMedGoogle Scholar
  13. 13.
    Chattopadhyay S, Deb B, Maiti S (2012) Hepatoprotective role of vitamin B(12) and folic acid in arsenic intoxicated rats. Drug Chem Toxicol 35:81–88CrossRefPubMedGoogle Scholar
  14. 14.
    Majumdar S, Chanda S, Ganguli B, Mazumder DN, Lahiri S, Dasgupta UB (2010) Arsenic exposure induces genomic hypermethylation. Environ Toxicol 25:315–318CrossRefPubMedGoogle Scholar
  15. 15.
    Bhattacharjee S, Sarkar C, Pal S (2013) Additive beneficial effect of folic acid and vitamin B12 co-administration on arsenic induced oxidative damage in cardiac tissue in vivo. Asian J Pharm Clin Res 6:64–69Google Scholar
  16. 16.
    Acharyya N, Sajed Ali S, Deb B, Chattopadhyay S, Maiti S (2014) Green tea (Camellia sinensis) alleviates arsenic-induced damages to DNA and intestinal tissues in rat and in situ intestinal loop by reinforcing antioxidant system. Environ Toxicol. doi: 10.1002/tox.21977 PubMedGoogle Scholar
  17. 17.
    Mukherjee S, Das D, Mukherjee M, Das AS, Mitra C (2006) Synergistic effect of folic acid and vitamin B12 in ameliorating arsenic-induced oxidative damage in pancreatic tissue of rat. J Nutr Biochem 17:319–327CrossRefPubMedGoogle Scholar
  18. 18.
    Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275PubMedGoogle Scholar
  19. 19.
    Copeland WH, Nealon DA, Rej R (1985) Effects of temperature on measurement of alkaline phosphatase activity. Clin Chem 31:185–190PubMedGoogle Scholar
  20. 20.
    Fossati P, Prencipe L, Berti G (1980) Use of 3,5-dichloro-2-hydroxybenzenesulfonic acid/4-aminophenazone chromogenic system in direct enzymic assay of uric acid in serum and urine. Clin Chem 26:227–231PubMedGoogle Scholar
  21. 21.
    Pardue HL, Bacon BL, Nevius MG, Skoug JW (1987) Kinetic study of the Jaffe reaction for quantifying creatinine in serum: 1. Alkalinity controlled with NaOH. Clin Chem 33:278–285PubMedGoogle Scholar
  22. 22.
    Fawcett JK, Scott JE (1960) A rapid and precise method for the determination of urea. J Clin Pathol 13:156–159PubMedCentralCrossRefPubMedGoogle Scholar
  23. 23.
    Buege JA, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–310CrossRefPubMedGoogle Scholar
  24. 24.
    Jendryczko A, Drozdz M (1988) Lipid peroxidation in the nuclear fraction of rat lungs induced by hydralazine. Neoplasma 35:37–40PubMedGoogle Scholar
  25. 25.
    Steinman HM (1978) The amino acid sequence of mangano superoxide dismutase from Escherichia coli. J Biol Chem 253:8708–8720PubMedGoogle Scholar
  26. 26.
    Sinha AK (1972) Colorimetric assay of catalase. Anal Biochem 47:389–394CrossRefPubMedGoogle Scholar
  27. 27.
    Forman HJ (2009) Critical methods in free radical biology & medicine. In: Free radical biology & medicine. United States, p S207Google Scholar
  28. 28.
    Pals J, Attene-Ramos MS, Xia M, Wagner ED, Plewa MJ (2013) Human cell toxicogenomic analysis linking reactive oxygen species to the toxicity of monohaloacetic acid drinking water disinfection byproducts. Environ Sci Technol 47:12514–12523PubMedCentralCrossRefPubMedGoogle Scholar
  29. 29.
    Terada LS, Leff JA, Repine JE (1990) Measurement of xanthine oxidase in biological tissues. Methods Enzymol 186:651–666CrossRefPubMedGoogle Scholar
  30. 30.
    Garcia-Martinez V, Macias D, Gañan Y, Garcia-Lobo JM, Francia MV, Fernandez-Teran MA, Hurle JM (1993) Internucleosomal DNA fragmentation and programmed cell death (apoptosis) in the interdigital tissue of the embryonic chick leg bud. J Cell Sci 106:201–208Google Scholar
  31. 31.
    Singh NP, McCoy MT, Tice RR, Schneider EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175:184–191CrossRefPubMedGoogle Scholar
  32. 32.
    Schmitt CJ, and Dethloff, GM (2000) Biomonitoring of Environmental Status and Trends (BEST) Program: selected methods for monitoring chemical contaminants in aquatic ecosystems. U.S. Geological Survey, Information and Technology Report USGS/BRD/ITR–2000-0005; 81 ppGoogle Scholar
  33. 33.
    Maiti S, Chatterjee AK (2000) Differential response of cellular antioxidant mechanism of liver and kidney to arsenic exposure and its relation to dietary protein deficiency. Environ Toxicol Pharmacol 8:227–235CrossRefPubMedGoogle Scholar
  34. 34.
    Maiti S, Chatterjee AK (2001) Effects on levels of glutathione and some related enzymes in tissues after an acute arsenic exposure in rats and their relationship to dietary protein deficiency. Arch Toxicol 75:531–537CrossRefPubMedGoogle Scholar
  35. 35.
    Santra A, Maiti A, Das S, Lahiri S, Charkaborty SK, Mazumder DN (2000) Hepatic damage caused by chronic arsenic toxicity in experimental animals. J Toxicol Clin Toxicol 38:395–405CrossRefPubMedGoogle Scholar
  36. 36.
    Bustamante J, Nutt L, Orrenius S, Gogvadze V (2005) Arsenic stimulates release of cytochrome c from isolated mitochondria via induction of mitochondrial permeability transition. Toxicol Appl Pharmacol 207:110–116CrossRefPubMedGoogle Scholar
  37. 37.
    Hernandez-Zavala A, Del Razo LM, Aguilar C, Garcia-Vargas GG, Borja VH, Cebrian ME (1998) Alteration in bilirubin excretion in individuals chronically exposed to arsenic in Mexico. Toxicol Lett 99:79–84CrossRefPubMedGoogle Scholar
  38. 38.
    Danielson C, Houseworth J, Skipworth E, Smith D, McCarthy L, Nanagas K (2006) Arsine toxicity treated with red blood cell and plasma exchanges. Transfusion 46:1576–1579CrossRefPubMedGoogle Scholar
  39. 39.
    Naranmandura H, Suzuki KT (2008) Formation of dimethylthioarsenicals in red blood cells. Toxicol Appl Pharmacol 227:390–399CrossRefPubMedGoogle Scholar
  40. 40.
    Karim MR, Salam KA, Hossain E, Islam K, Ali N, Haque A, Saud ZA, Yeasmin T, Hossain M, Miyataka H, Himeno S, Hossain K (2010) Interaction between chronic arsenic exposure via drinking water and plasma lactate dehydrogenase activity. Sci Total Environ 409:278–283CrossRefPubMedGoogle Scholar
  41. 41.
    Messarah M, Saoudi M, Boumendjel A, Kadeche L, Boulakoud MS, El Feki A (2013) Green tea extract alleviates arsenic-induced biochemical toxicity and lipid peroxidation in rats. Toxicol Ind Health 29:349–359CrossRefPubMedGoogle Scholar
  42. 42.
    Zamora PL, Rockenbauer A, Villamena FA (2014) Radical model of arsenic(III) toxicity: theoretical and EPR spin trapping studies. Chem Res Toxicol 27:765–774CrossRefPubMedGoogle Scholar
  43. 43.
    Faraci FM, Didion SP (2004) Vascular protection: superoxide dismutase isoforms in the vessel wall. Arterioscler Thromb Vasc Biol 24:1367–1373CrossRefPubMedGoogle Scholar
  44. 44.
    Lambrou A, Baccarelli A, Wright RO, Weisskopf M, Bollati V, Amarasiriwardena C, Vokonas P, Schwartz J (2012) Arsenic exposure and DNA methylation among elderly men. Epidemiology (Cambridge, Mass) 23:668–676CrossRefGoogle Scholar
  45. 45.
    Spiegelstein O, Lu X, Le XC, Troen A, Selhub J, Melnyk S, James SJ, Finnell RH (2003) Effects of dietary folate intake and folate binding protein-1 (Folbp1) on urinary speciation of sodium arsenate in mice. Toxicol Lett 145:167–174CrossRefPubMedGoogle Scholar
  46. 46.
    Vahter M, Marafante E (1987) Effects of low dietary intake of methionine, choline or proteins on the biotransformation of arsenite in the rabbit. Toxicol Lett 37:41–46CrossRefPubMedGoogle Scholar
  47. 47.
    Buchet JP, Lauwerys R, Roels H (1981) Comparison of the urinary excretion of arsenic metabolites after a single oral dose of sodium arsenite, monomethylarsonate, or dimethylarsinate in man. Int Arch Occup Environ Health 48:71–79CrossRefPubMedGoogle Scholar
  48. 48.
    Vahter M, Concha G (2001) Role of metabolism in arsenic toxicity. Pharmacol Toxicol 89:1–5CrossRefPubMedGoogle Scholar
  49. 49.
    Ercal N, Gurer-Orhan H, Aykin-Burns N (2001) Toxic metals and oxidative stress part I: mechanisms involved in metal-induced oxidative damage. Curr Top Med Chem 1:529–539CrossRefPubMedGoogle Scholar
  50. 50.
    Valinluck V, Tsai HH, Rogstad DK, Burdzy A, Bird A, Sowers LC (2004) Oxidative damage to methyl-CpG sequences inhibits the binding of the methyl-CpG binding domain (MBD) of methyl-CpG binding protein 2 (MeCP2). Nucleic Acids Res 32:4100–4108PubMedCentralCrossRefPubMedGoogle Scholar
  51. 51.
    Pogribny IP, Tryndyak VP, Woods CG, Witt SE, Rusyn I (2007) Epigenetic effects of the continuous exposure to peroxisome proliferator WY-14,643 in mouse liver are dependent upon peroxisome proliferator activated receptor alpha. Mutat Res 625:62–71PubMedCentralCrossRefPubMedGoogle Scholar
  52. 52.
    Maiti S, Chattopadhyay S, Acharyya N, Deb B, Hati A (2014) Emblica officinalis (amla) ameliorates arsenic-induced liver damage via DNA protection by antioxidant systems. Mol Cell Toxicol 10:75–82CrossRefGoogle Scholar
  53. 53.
    Villa-Bellosta R, Sorribas V (2010) Arsenate transport by sodium/phosphate cotransporter type IIb. Toxicol Appl Pharmacol 247:36–40CrossRefPubMedGoogle Scholar
  54. 54.
    Murer H, Forster I, Biber J (2004) The sodium phosphate cotransporter family SLC34. Pflugers Arch - Eur J Physiol 447:763–767CrossRefGoogle Scholar
  55. 55.
    Virkki LV, Biber J, Murer H, Forster IC (2007) Phosphate transporters: a tale of two solute carrier families. Am J Physiol Renal Physiol 293:F643–F654CrossRefPubMedGoogle Scholar
  56. 56.
    Moore SA, Moennich DM, Gresser MJ (1983) Synthesis and hydrolysis of ADP-arsenate by beef heart submitochondrial particles. J Biol Chem 258:6266–6271PubMedGoogle Scholar
  57. 57.
    Nielsen F, Mikkelsen BB, Nielsen JB, Andersen HR, Grandjean P (1997) Plasma malondialdehyde as biomarker for oxidative stress: reference interval and effects of life-style factors. Clin Chem 43:1209–1214PubMedGoogle Scholar
  58. 58.
    Li M, Cai JF, Chiu JF (2002) Arsenic induces oxidative stress and activates stress gene expressions in cultured lung epithelial cells. J Cell Biochem 87:29–38CrossRefPubMedGoogle Scholar
  59. 59.
    Shila S, Subathra M, Devi MA, Panneerselvam C (2005) Arsenic intoxication-induced reduction of glutathione level and of the activity of related enzymes in rat brain regions: reversal by DL-alpha-lipoic acid. Arch Toxicol 79:140–146CrossRefPubMedGoogle Scholar
  60. 60.
    Santra A, Chowdhury A, Ghatak S, Biswas A, Dhali GK (2007) Arsenic induces apoptosis in mouse liver is mitochondria dependent and is abrogated by N-acetylcysteine. Toxicol Appl Pharmacol 220:146–155CrossRefPubMedGoogle Scholar
  61. 61.
    Steinmaus C, Ferreccio C, Acevedo J, Yuan Y, Liaw J, Duran V, Cuevas S, Garcia J, Meza R, Valdes R, Valdes G, Benitez H, VanderLinde V, Villagra V, Cantor KP, Moore LE, Perez SG, Steinmaus S, Smith AH (2014) Increased lung and bladder cancer incidence in adults after in utero and early-life arsenic exposure. Cancer Epidemiol, Biomark Prev: Publ Am Assoc Cancer Res 23:1529–1538Google Scholar
  62. 62.
    Kligerman AD, Doerr CL, Tennant AH (2005) Oxidation and methylation status determine the effects of arsenic on the mitotic apparatus. Mol Cell Biochem 279:113–121CrossRefPubMedGoogle Scholar
  63. 63.
    Kligerman AD, Doerr CL, Tennant AH, Harrington-Brock K, Allen JW, Winkfield E, Poorman-Allen P, Kundu B, Funasaka K, Roop BC, Mass MJ, DeMarini DM (2003) Methylated trivalent arsenicals as candidate ultimate genotoxic forms of arsenic: induction of chromosomal mutations but not gene mutations. Environ Mol Mutagen 42:192–205CrossRefPubMedGoogle Scholar
  64. 64.
    Gurr JR, Liu F, Lynn S, Jan KY (1998) Calcium-dependent nitric oxide production is involved in arsenite-induced micronuclei. Mutat Res 416:137–148CrossRefPubMedGoogle Scholar
  65. 65.
    Vermeulen K, Van Bockstaele DR, Berneman ZN (2005) Apoptosis: mechanisms and relevance in cancer. Ann Hematol 84:627–639CrossRefPubMedGoogle Scholar
  66. 66.
    Cutler RG (1984) Urate and ascorbate: their possible roles as antioxidants in determining longevity of mammalian species. Arch Gerontol Geriatr 3:321–348CrossRefPubMedGoogle Scholar
  67. 67.
    Toncev G (2006) Therapeutic value of serum uric acid levels increasing in the treatment of multiple sclerosis. Vojnosanit Pregl Mil-Med Pharm Rev 63:879–882CrossRefGoogle Scholar
  68. 68.
    Zhang TC, Schmitt MT, Mumford JL (2003) Effects of arsenic on telomerase and telomeres in relation to cell proliferation and apoptosis in human keratinocytes and leukemia cells in vitro. Carcinogenesis 24:1811–1817CrossRefPubMedGoogle Scholar
  69. 69.
    Jauge P, Del-Razo LM (1985) Uric acid levels in plasma and urine in rats chronically exposed to inorganic As (III) and As(V). Toxicol Lett 26:31–35CrossRefPubMedGoogle Scholar
  70. 70.
    Aposhian HV, Zakharyan RA, Avram MD, Kopplin MJ, Wollenberg ML (2003) Oxidation and detoxification of trivalent arsenic species. Toxicol Appl Pharmacol 193:1–8CrossRefPubMedGoogle Scholar
  71. 71.
    Sharma S, Singh AK, Kaushik S, Sinha M, Singh RP, Sharma P, Sirohi H, Kaur P, Singh TP (2013) Lactoperoxidase: structural insights into the function, ligand binding and inhibition. Int J Biochem Mol Biol 4:108–128PubMedCentralPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Nirmallya Acharyya
    • 1
    • 2
    • 3
  • Bimal Deb
    • 3
  • Sandip Chattopadhyay
    • 3
  • Smarajit Maiti
    • 1
    • 2
    • 4
  1. 1.Department of BiochemistryCell and Molecular Therapeutics Laboratory, Oriental Institute of Science and TechnologyVidyasagar UniversityMidnaporeIndia
  2. 2.Department of Biotechnology, Oriental Institute of Science and TechnologyVidyasagar UniversityMidnaporeIndia
  3. 3.Department of Biomedical Laboratory Science and Management, (UGC Innovative Department)Vidyasagar UniversityMidnaporeIndia
  4. 4.Epidemiology and Human Health DivisionAgricure Biotech Research SocietyMidnaporeIndia

Personalised recommendations