Skip to main content
Log in

Effect of Selenomethionine Supplementation in Food on the Excretion and Toxicity of Arsenic Exposure in Female Mice

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Selenium (Se) is an essential component of several major metabolic pathways and controls immune function. Arsenic (As) is a human carcinogen with immunotoxic and genotoxic activities, functioning mainly by producing oxidative stress. Due to the ability of Se to interact with As and to possibly block its toxic effects, we investigated the impact of dietary Se-methionine (Se-Met) supplementation on the toxicity of As exposure in vivo in a mouse model. Sufficient and excess levels of Se-Met (0.2 and 2 ppm, respectively) were fed to C57BL/6N female mice exposed to sodium arsenite (3, 6 and 10 mg/kg) in tap water for 9 days. We observed that As exposure increased Se-Met excretion in the urine. Se-Met supplementation increased the relative liver weight and decreased the concentration of total liver proteins in animals exposed to 10 mg/kg of As. Se-Met supplementation maintained a normal pool of glutathione in the liver and increased glutathione peroxidase concentration, although the lipoperoxidation level was increased by Se-Met even without As exposure. Se-Met supplementation helped to maintain the CD4/CD8 ratio of lymphocytes in the spleen, although it increased the proportion of B cells. Se-Met supplementation prior to As exposure increased the secretion of interleukin-4, IL-12 and interferon-γ and the stimulation index of the spleen cells in in vitro assays. Se-Met intake improved the basal immunological parameters but did not reduce the damage caused by oxidative stress after low-dose As exposure.

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

Similar content being viewed by others

References

  1. Rafferty TS, Walker C, Hunter JA, Beckett GJ, McKenzie RC (2002) Inhibition of ultraviolet B radiation-induced interleukin 10 expression in murine keratinocytes by selenium compounds. Br J Dermatan 146:485–489. doi:10.1046/j.1365-2133.2002.04586.x

    Article  CAS  Google Scholar 

  2. Vega L, Rodríguez-Sosa M, García-Montalvo EA, Del Razo LM, Elizondo G (2007) Seleno-methionine levels in the diet modulate the activation status and spleen cells populations depending on its concentration in female mice. Food Chem Topical 45:1147–1153. doi:10.1016/j.fct.2006.12.021

    CAS  Google Scholar 

  3. Badmaev V, Majeed M, Passwater RA (1996) Selenium: a quest for better understanding. Alter There Health Med 2:59–67

    CAS  Google Scholar 

  4. Spallholz JE (1990) Selenium and glutathione peroxidase: essential nutrient and antioxidant component of the immune system. Adv Exp Med Biol 262:145–158

    PubMed  CAS  Google Scholar 

  5. Dusinska M, Vallova B, Ursinyova M, Hladikova V, Smolkova B, Wsolova L, Raslova K, Collins AR (2002) DNA damage and antioxidants; fluctuations through the year in a central European population group. Food Chem Topical 40:1119–1123. doi:10.1016/S0278-6915(02)00055-8

    CAS  Google Scholar 

  6. Keck AS, Finley JW (2006) Aqueous extracts of selenium-fertilized broccoli increase selenoprotein activity and inhibit DNA single-strand breaks, but decrease the activity of quinine reductase in Hepa 1c1c7 cells. Food Chem Topical 44:695–703. doi:10.1016/j.fct.2005.10.002d

    CAS  Google Scholar 

  7. Gonsebatt ME, Vega L, Salazar AM, Montero R, Guzmán P, Blas J, Del Razo LM, García-Vargas G, Albores A, Cebrián ME, Kelsh M, Ostrosky-Wegman P (1997) Cytogenetic effects in human exposure to arsenic. Mutat Res 386:219–228. doi:10.1016/S1383-5742(97)00009-4

    Article  PubMed  CAS  Google Scholar 

  8. Ostrosky-Wegman P, Gonsebatt ME, Montero R, Vega L, Barba H, Espinosa J, Palao A, Cortinas C, García-Vargas G, Del Razo LM, Cebrián ME (1991) Lymphocyte proliferation kinetics and genotoxic findings in a pilot study on individuals chronically exposed to arsenic in Mexico. Mutat Res 250:477–482. doi:10.1016/0027-5107(91)90204-2

    Article  PubMed  CAS  Google Scholar 

  9. Vega L, Gonsebatt ME, Ostrosky-Wegman P (1995) Aneugenic effect of sodium arsenite on human lymphocytes in vitro: an individual susceptibility effect detected. Mutat Res 334:365–373. doi:10.1016/0165-1161(95)90074-8

    Article  PubMed  CAS  Google Scholar 

  10. Kitchin KT, Ahmad S (2003) Oxidative stress as a possible mode of action for arsenic carcinogenesis. Topical Lett 137:3–13. doi:10.1016/S0378-4274(02)00376-4

    CAS  Google Scholar 

  11. Valko M, Morris H, Cronin MTD (2005) Metals, toxicity and oxidative stress. Curr Med Chem 12:1161–1208. doi:10.2174/0929867053764635

    Article  PubMed  CAS  Google Scholar 

  12. Manley SA, George GN, Pickering IJ, Glass RS, Prenner EJ, Yamdagni R, Wu Q, Gailer J (2006) The seleno bis(S-glutathionyl) arsinum ion is assembled in erythrocyte lysate. Chem Res Topical 19:601–607. doi:10.1021/tx0503505

    CAS  Google Scholar 

  13. Yeh JY, Cheng LC, Liang YC, Ou BR (2003) Modulation of the arsenic effects on cytotoxicity, viability, and cell cycle in porcine endothelial cells by selenium. Endothelium 10:127–139. doi:10.1080/10623320390233391

    Article  PubMed  CAS  Google Scholar 

  14. Chattopadhyay S, Pal-Ghosh S, Ghosh D, Debnath J (2003) Effect of dietary co-administration of sodium selenite on sodium arsenite-induced ovarian and uterine disorders in mature albino rats. Topical Sci 75:412–422. doi:10.1093/toxsci/kfg194

    CAS  Google Scholar 

  15. Patterson R, Vega L, Trouba K, Bortner C, Germolec D (2004) Arsenic-induced alterations in the contact hypersensitivity response in Balb/c mice. Topical Appl Pharmacol 198:434–443. doi:10.1016/j.taap.2003.10.012

    Article  CAS  Google Scholar 

  16. Soto-Peña GA, Luna AL, Acosta-Saavedra L, Conde P, López-Carrillo L, Cebrián ME, Bastida M, Calderón-Aranda ES, Vega L (2006) Assessment of lymphocyte subpopulations and cytokine secretion in children exposed to arsenic. FASEB J 20:779–781. doi:10.1096/fj.05-4860fje

    PubMed  Google Scholar 

  17. Soto-Peña GA, Vega L (2008) Arsenic interferes with the signaling transduction pathway of T cell receptor activation by increasing basal and induced phosphorylation of Lck and Fyn in spleen cells. Topical Appl Pharmacol 230:216–226. doi:10.1016/j.taap.2008.02.029

    Article  Google Scholar 

  18. Vega L, Ostrosky-Wegman P, Fortoul TI, Díaz C, Madrid V, Saavedra R (1999) Sodium arsenite reduces proliferation of human activated T-cells by inhibition of the secretion of interleukin-2. Immunopharmacol Immunotoxicol 21:203–220. doi:10.3109/08923979909052758

    Article  PubMed  CAS  Google Scholar 

  19. Vega L, Styblo M, Patterson R, Cullen W, Wang C, Germolec D (2001) Differential effects of trivalent and pentavalent arsenicals on cell proliferation and cytokine secretion in normal human epidermal keratinocytes. Topical Appl Pharmacol 172:225–232. doi:10.1006/taap.2001.9152

    Article  CAS  Google Scholar 

  20. Vega L, Montes de Oca P, Saavedra R, Ostrosky-Wegman P (2004) Helper T cell subpopulations from women are more susceptible to the toxic effect of sodium arsenite in vitro. Toxicology 199:121–128. doi:10.1016/j.tox.2004.02.012

    Article  PubMed  CAS  Google Scholar 

  21. Tinggi U (2003) Essentiality and toxicity of selenium and its status in Australia: a review. Topical Lett 137:103–110. doi:10.1016/S0378-4274(02)00384-3

    CAS  Google Scholar 

  22. Gregory JF, Edds GT (1984) Effect of dietary selenium on the metabolism of aflatoxin B1 in turkeys. Food Chem Topical 22:637–642. doi:10.1016/0278-6915(84)90272-2

    CAS  Google Scholar 

  23. Vega L (2009) Effects of arsenic exposure on the immune system and mechanism of action. In: Gosselin JD, Fancher IM (eds) Environmental health risks: Lead poisoning and arsenic exposure. NovaScience, USA, pp 155–166

    Google Scholar 

  24. Hughes MF, Kenyon EM, Edwards BC, Mitchell CT, Razo LM, Thomas DJ (2003) Accumulation and metabolism of arsenic in mice after repeated oral administration of arsenate. Topical Appl Pharmacol 191:202–210. doi:10.1016/S0041-008X(03)00249-7

    Article  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  26. Paglia DE, Valentine WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70:158–169

    PubMed  CAS  Google Scholar 

  27. Buege JA, Aust SD (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–310

    PubMed  CAS  Google Scholar 

  28. Levander OA (1985) Considerations on the assessment of selenium status. Fed Proceed 44:2579–2583

    CAS  Google Scholar 

  29. Styblo M, Thomas DJ (2001) Selenium modifies the metabolism and toxicity of arsenic in primary rat hepatocytes. Topical Appl Pharmacol 172:52–61. doi:10.1006/taap.2001.9134

    Article  CAS  Google Scholar 

  30. Frost DV (1983) What do losses in selenium and arsenic bioavailability signify for health? Sci Total Environ 28:455–466. doi:10.1016/S0048-9697(83)80042-4

    Article  PubMed  CAS  Google Scholar 

  31. Molin Y, Frisk P, Ilbäck NG (2008) Sequential effects of daily arsenic trioxide treatment on essential and nonessential trace elements in tissues in mice. Anticancer Drugs 19:812–818. doi:10.1097/CAD.0b013e32830c456b

    Article  PubMed  CAS  Google Scholar 

  32. Ganyc D, Talbot S, Konate F, Jackson S, Schanen B, Cullen W, Self WT (2007) Impact of trivalent arsenicals on selenoprotein synthesis. Environ Health Perspect 115:346–353. doi:10.1289/ehp.9440

    Article  PubMed  CAS  Google Scholar 

  33. Sun E, Xu H, Wen D, Zuo P, Zhou J, Wang J (1997) Inhibition of lipid peroxidation. Biol Trace Elem Res 59:87–92. doi:10.1007/BF02783233

    Article  PubMed  CAS  Google Scholar 

  34. Mukhopadhyay-Sardar S, Rana MP, Chatterjee M (2000) Antioxidant associated chemoprevention by selenomethionine in murine tumor model. Mol Cell Biochem 206:17–25. doi:10.1023/A:1007040705928

    Article  PubMed  CAS  Google Scholar 

  35. Matés JM, Segura JA, Alonso FJ, Márquez J (2008) Intracellular redox status and oxidative stress: implications for cell proliferation, apoptosis, and carcinogenesis. Arch Topical 82:273–299. doi:10.1007/s00204-008-0304-z

    Google Scholar 

  36. Stazi AV, Trinti B (2008) Selenium deficiency in celiac disease: risk of autoimmune thyroid diseases. Minerva Med 99:643–653. doi:10.4415/ann-10-04-06

    PubMed  CAS  Google Scholar 

  37. Hughes DA (1999) Effects of dietary antioxidants on the immune function of middle-aged adults. Proc Nutr Soc 58:79–84. doi:10.1079/PNS19990012

    Article  PubMed  CAS  Google Scholar 

  38. Nakamura K, Yube K, Miyatake A, Cambier JC, Hirashima M (2003) Involvement of CD4 D3-D4 membrane proximal extracellular domain for the inhibitory effect of oxidative stress on activation-induced CD4 down-regulation and its possible role for T cell activation. Mol Immunol 39:909–921. doi:10.1016/S0161-5890(03)00030-0

    Article  PubMed  CAS  Google Scholar 

  39. Parízek J (1990) Health effects of dietary selenium. Food Chem Topical 28:763–765

    Google Scholar 

Download references

Acknowledgments

This work was partially supported by the National Council of Research and Technology (Connacht), Mexico (48787-M).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Libia Vega.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rodríguez-Sosa, M., García-Montalvo, E.A., Del Razo, L.M. et al. Effect of Selenomethionine Supplementation in Food on the Excretion and Toxicity of Arsenic Exposure in Female Mice. Biol Trace Elem Res 156, 279–287 (2013). https://doi.org/10.1007/s12011-013-9855-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-013-9855-9

Keywords

Navigation