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Selenium Source Impacts Protection of Porcine Jejunal Epithelial Cells from Cadmium-Induced DNA Damage, with Maximum Protection Exhibited with Yeast-Derived Selenium Compounds

Abstract

Selenium (Se) is found in inorganic and organic forms, both of which are commonly used in animal feed supplements. The aim of this study was to determine the impact of the chemical form of Se on its associated ameliorative effects on cadmium (Cd)-induced DNA damage in a porcine model. At a cellular level, Cd mediates free oxygen radical production leading in particular to DNA damage, with consequential mutagenesis and inhibition of DNA replication. In this study, porcine jejunal epithelial cells (IPEC-J2) were pre-incubated for 48 h with one of Se-yeast (Sel-Plex), selenomethionine (Se-M), sodium selenite (Se-Ni) or sodium selenate (Se-Na). The effects of this supplementation on cell viability and DNA damage following cadmium chloride (CdCl2) exposure were subsequently evaluated. IPEC-J2 cells were cultivated throughout in medium supplemented with porcine serum to generate a superior model that recapitulated the porcine gut epithelium. The results illustrated that Se antioxidant effects were both composition- and dose-dependent as evident from cell viability (Alamar Blue and 5-carboxyfluorescein diacetate acetoxymethyl ester) and DNA damage assays (Comet and TUNEL). Both the Se-yeast and Se-M organic species, when used at the European Food Safety Authority guideline levels, had a protective effect against Cd-induced DNA damage in the IPEC-J2 model system whereas for inorganic Se-Ni and Se-Na sources no protective effects were observed and in fact these were shown to enhance the negative effects of Cd-induced DNA damage. It can be concluded that nutritional supplementation with organoselenium may protect porcine gut integrity from damage induced by Cd.

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References

  1. Scientific Opinion of the Panel on Contaminants in the Food Chain on a request from the European Commission on cadmium in food. EFSA Journal (2009) 980, 1–139. doi:10.2903/j.efsa.2009.980

  2. European Food Safety Authority (2012) Cadmium dietary exposure in the European population. EFSA J 10(1):2551–2588. doi:10.2903/j.efsa.2012.2551

    Article  Google Scholar 

  3. Fasanya-Odewumi C, Latinwo LM, Ikediobi CO, Gilliard L, Sponholtz G, Nwoga J, Stino F, Hamilton N, Erdos GW (1998) The genotoxicity and cytotoxicity of dermally-administered cadmium: effects of dermal cadmium administration. Int J Mol Med 1:1001–1007. doi:10.3892/ijmm.1.6.1001

    CAS  PubMed  Google Scholar 

  4. Bertin G, Averbeck D (2006) Cadmium: cellular effects, modifications of biomolecules, modulation of DNA repair and genotoxic consequences (a review). Biochimie 88:1549–1559. doi:10.1016/j.biochi.2006.10.001

    CAS  Article  PubMed  Google Scholar 

  5. Bampidis VA, Nistor E, Nitas D (2013) Arsenic, cadmium, lead and mercury as undesirable substances in animal feeds. Sci Pap Anim Sci Biotechnol 46:17–22

    Google Scholar 

  6. Bergeron PM, Jumarie C (2006) Characterization of cadmium uptake in human intestinal crypt cells HIEC in relation to inorganic metal speciation. Toxicology 219:156–166. doi:10.1016/j.tox.2005.11.016

    CAS  Article  PubMed  Google Scholar 

  7. Ninkov M, Popov A, Demenesku J, Mirkov I, Mileusnic D, Petrovic A, Grigorov I, Zolotarevski L, Tolinacki M, Kataranovski D, Brceski I, Kataranovski M (2015) Toxicity of oral cadmium intake: impact on gut immunity. Toxicol Lett 237:89–99. doi:10.1016/j.toxlet.2015.06.002

    CAS  Article  PubMed  Google Scholar 

  8. McKelvey SM, Horgan KA, Murphy RA (2014) Chemical form of selenium differentially influences DNA repair pathways following exposure to lead nitrate. J Trace Elem Med Biol. doi:10.1016/j.jtemb.2014.06.005

    PubMed  Google Scholar 

  9. Zeng H, Combs GF (2008) Selenium as an anticancer nutrient: roles in cell proliferation and tumor cell invasion. J Nutr Biochem 19:1–7. doi:10.1016/j.jnutbio.2007.02.005

    Article  PubMed  Google Scholar 

  10. Brummer M, Hayes S, Dawson KA, Lawrence LM (2013) Measures of antioxidant status of the horse in response to selenium depletion and repletion. J Anim Sci 91:2158–2168. doi:10.2527/jas.2012-5794

    CAS  Article  PubMed  Google Scholar 

  11. Ward P, Connolly C, Murphy R (2013) Accelerated determination of selenomethionine in selenized yeast: validation of analytical method. Biol Trace Elem Res 151:446–450. doi:10.1007/s12011-012-9571-x

    CAS  Article  PubMed  Google Scholar 

  12. Ishii M, Ogata H, Shimizu H, Takeuchi Y, Nozawa T, Yamamoto Y, Okamoto T, Shimamura T, Utsumi A, Jitsukawa T, Endo M (2002) Effects of vitamin E and selenium administration on pregnant, heavy draft mares on placental retention time and reproductive performance and on white muscle disease in their foals. J Equine Vet Sci 22:213–220. doi:10.1053/jevs.2002.34302

    Article  Google Scholar 

  13. Galbraith ML, Vorachek WR, Estill CT, Whanger PD, Bobe G, Davis TZ, Hall JA (2015) Rumen microorganisms decrease bioavailability of inorganic selenium supplements. Biol Trace Elem Res 171:338–343. doi:10.1007/s12011-015-0560-8

    Article  PubMed  Google Scholar 

  14. O'Dell BL, Sunde RA 1997 Handbook of nutritionally essential minerals. New York: Marcel Dekker, Inc; 275–334. ISBN 0–8247–9312-9

  15. De Rosa V, Erkekoğlu P, Forestier A, Favier A, Hincal F, Diamond AM, Douki TRW (2012) Low doses of selenium specifically stimulate the repair of oxidative DNA damage in LNCaP prostate cancer cells. Free Radic Res 46:105–116. doi:10.3109/10715762.2011.647009

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  16. Liu L, Yang B, Cheng Y, Lin H (2015) Ameliorative effects of selenium on cadmium-induced oxidative stress and endoplasmic reticulum stress in the chicken kidney. Biol Trace Elem Res 167:308–319. doi:10.1007/s12011-015-0314-7

    CAS  Article  PubMed  Google Scholar 

  17. Jabeen F, Chaudhry AS (2011) Effects of cadmium chloride and sodium selenite alone or in combination on the liver of male Sprague-Dawley rats assessed by different assays. Biol Trace Elem Res 143:1077–1090. doi:10.1007/s12011-010-8946-0

    CAS  Article  PubMed  Google Scholar 

  18. Yu, RA, Chen X (2004) Effect of selenium on rat hepatocellular DNA damage induced by cadmium in vitro. Chinese J Prev Med 38:29–32. doi: DOI:. 10.3760/J: ISSN: 0253–9624.2004.01.009

  19. Bolkent S, Koyuturk M, Bulan OK, Tunali S, Yanardag R, Tabakoglu AO (2007) The effects of combined alpha-tocopherol, ascorbic acid, and selenium against cadmium toxicity in rat intestine. J Environ Pathol Toxicol Oncol 26:21–27

    CAS  Article  PubMed  Google Scholar 

  20. Forrester LW, Latinwo LM, Fasanya-Odewumi C, Ikediobi C, Abazinge MD, Mbuya O, Nwoga J (2000) Comparative studies of cadmium-induced single strand breaks in female and male rats and the ameliorative effect of selenium. Int J Mol Med 6:449–501. doi:10.3892/ijmm.6.4.449

    CAS  PubMed  Google Scholar 

  21. Schrauzer GN, Surai PF (2009) Selenium in human and animal nutrition: resolved and unresolved issues. A partly historical treatise in commemoration of the fiftieth anniversary of the discovery of the biological essentiality of selenium, dedicated to the memory of Klaus Schwarz (1914-1978). Crit Rev Biotechnol 29:2–9. doi:10.1080/07388550902728261

    CAS  Article  PubMed  Google Scholar 

  22. Surai PF, Fisinin VI (2016) Selenium in sow nutrition. Anim Feed Sci Technol 211:18–30. doi:10.1016/j.anifeedsci.2015.11.006

    CAS  Article  Google Scholar 

  23. Hamilton-Koch W, Snyder RD, Lavelle JM (1985) Metal-induced DNA damage and repair in human diploid fibroblasts and Chinese hamster ovary cells. Chem Biol Interact 59:17–28. doi:10.1016/S0009-2797(86)80052-7

    Article  Google Scholar 

  24. Bera S, De Rosa V, Rachidi W, Diamond AM (2013) Does a role for selenium in DNA damage repair explain apparent controversies in its use in chemoprevention? Mutagenesis 28:127–134. doi:10.1093/mutage/ges064

    CAS  Article  PubMed  Google Scholar 

  25. Geens MM, Niewold TA (2011) Optimizing culture conditions of a porcine epithelial cell line IPEC-J2 through a histological and physiological characterization. Cytotechnology 63:415–423. doi:10.1007/s10616-011-9362-9

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  26. Schierack P, Nordhoff M, Pollmann M, Weyrauch KD, Amasheh S, Lodemann U, Jores J, Tachu B, Kleta S, Blikslager A, Tedin K, Wieler LH (2006) Characterization of a porcine intestinal epithelial cell line for in vitro studies of microbial pathogenesis in swine. Histochem Cell Biol 125:293–305. doi:10.1007/s00418-005-0067-z

    CAS  Article  PubMed  Google Scholar 

  27. Zakrzewski SS, Richter JF, Krug SM, Jebautzke B, Lee IF, Rieger J, Sachtleben M, Bondzio A, Schulzke JD, Fromm M, Günzel D (2013) Improved cell line IPEC-J2, characterized as a model for porcine jejunal epithelium. PLoS One 8:e79643. doi:10.1371/journal.pone.0079643

    Article  PubMed  PubMed Central  Google Scholar 

  28. Bopp SK, Lettieri T (2008) Comparison of four different colorimetric and fluorometric cytotoxicity assays in a zebrafish liver cell line. BMC Pharmacol 11:1–11. doi:10.1186/1471-2210-8-8

    Google Scholar 

  29. Gyori BM, Venkatachalam G, Thiagarajan PS, Hsu D, Clement M (2014) Redox Biology OpenComet : an automated tool for comet assay image analysis. Redox Biol 2:457–465. doi:10.1016/j.redox.2013.12.020

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  30. Azqueta A, Collins AR (2013) The essential comet assay: a comprehensive guide to measuring DNA damage and repair. Arch Toxicol 87:949–968. doi:10.1007/s00204-013-1070-0

    CAS  Article  PubMed  Google Scholar 

  31. Nandhakumar S, Parasuraman S, Shanmugam MM, Rao KR, Chand P, Bhat BV (2011) Evaluation of DNA damage using single-cell gel electrophoresis (comet assay). J Pharmacol Pharmacother 2(2):107–111. doi:10.4103/0976-500X.81903

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  32. Zhou YJ, Zhang SP, Liu CW, Cai YQ (2009) The protection of selenium on ROS mediated-apoptosis by mitochondria dysfunction in cadmium-induced LLC-PK(1) cells. Toxicol in Vitro 23:288–294. doi:10.1016/j.tiv.2008.12.009

    Article  PubMed  Google Scholar 

  33. Lawal AO, Ellis E (2010) Differential sensitivity and responsiveness of three human cell lines HepG2 , 1321N1 and HEK 293 to cadmium. J Toxicol Sci 35:465–478. doi:10.2131/jts.35.465

    CAS  Article  PubMed  Google Scholar 

  34. Letavayova L, Vlckova V, Brozmanova J (2006) Selenium : from cancer prevention to DNA damage. Toxicology 227:1–14. doi:10.1016/j.tox.2006.07.017

    CAS  Article  PubMed  Google Scholar 

  35. Fernandes AP, Gandin V (2015) Selenium compounds as therapeutic agents in cancer. Biochim Biophys Acta 1850:1642–1660. doi:10.1016/j.bbagen.2014.10.008

    CAS  Article  PubMed  Google Scholar 

  36. EFSA panel on additives and products or substances used in animal feed (FEEDAP) (2011) Scientific opinion on safety and efficacy of Sel-Plex ® (organic form of selenium produced by Saccharomyces cerevisiae CNCM I-3060 ) for all species. 9:1–52. doi: 10.2903/j.efsa.2011.2110.

  37. Shen HM, Yang CF, Ong CN (1999) Sodium selenite-induced oxidative stress and apoptosis in human hepatoma HepG2 cells. Int J Cancer 81:820–828. doi:10.1002/(SICI)1097-0215(19990531)81:5<820::AID-IJC25>3.0.CO;2-F

    CAS  Article  PubMed  Google Scholar 

  38. Bandura L, Drukala J, Wolnicka-Glubisz A, Björnstedt M, Korohoda W (2005) Differential effects of selenite and selenate on human melanocytes, keratinocytes and melanoma cells. Biochem Cell Biol 211:196–211. doi:10.1139/O04-130

    Article  Google Scholar 

  39. Speit G, Hartmann A (2006) The comet assay: a sensitive genotoxicity test for the detection of DNA damage and repair. Methods Mol Biol 314:275–286. doi:10.1385/1-59259-973-7:275

    CAS  Article  PubMed  Google Scholar 

  40. Lavu RVS, Van de Wiele T, Pratti VL, Tack F, Du Laing G (2016) Selenium bioaccessibility in stomach, small intestine and colon: comparison between pure Se compounds, Se-enriched food crops and food supplements. Food Chem 197:382–387. doi:10.1016/j.foodchem.2015.08.001

    CAS  Article  PubMed  Google Scholar 

  41. Devos C, Sandra K, Sandra P (2002) Capillary gas chromatography inductively coupled plasma mass spectrometry (CGC-ICPMS) for the enantiomeric analysis of D,L-selenomethionine in food supplements and urine. J Pharm Biomed Anal 27:507–514. doi:10.1016/S0731-7085(01)00576-3

    CAS  Article  PubMed  Google Scholar 

  42. Barger JL, Kayo T, Pugh TD, Vann JA, Power R, Dawson K, Weindruch R, Prolla TA (2012) Gene expression profiling reveals differential effects of sodium selenite, selenomethionine, and yeast-derived selenium in the mouse. Genes Nutr 7:155–165. doi:10.1007/s12263-011-0243-9

    CAS  Article  PubMed  Google Scholar 

  43. Shi K, Jiang Q, Li Z, Shan L, Li F, An J, Yang Y, Xu C (2013) Sodium selenite alters microtubule assembly and induces apoptosis in vitro and in vivo. J Hematol Oncol 6:1–9. doi:10.1186/1756-8722-6-7

    CAS  Article  Google Scholar 

  44. Gu P, Bernhard D (2016) Cadmium overkill: autophagy, apoptosis and necrosis signalling in endothelial cells exposed to cadmium. Cell Mol Life Sci 73:1699–1713. doi:10.1007/s00018-015-2094-9

    Article  Google Scholar 

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Acknowledgments

SL is the recipient of a postgraduate studentship from Alltech Ltd.

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Correspondence to Dermot Walls.

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Blanaid White and Dermot Walls made an equal contribution to this work.

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Lynch, S.J., Horgan, K.A., White, B. et al. Selenium Source Impacts Protection of Porcine Jejunal Epithelial Cells from Cadmium-Induced DNA Damage, with Maximum Protection Exhibited with Yeast-Derived Selenium Compounds. Biol Trace Elem Res 176, 311–320 (2017). https://doi.org/10.1007/s12011-016-0828-7

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  • DOI: https://doi.org/10.1007/s12011-016-0828-7

Keywords

  • Selenium
  • Cadmium
  • DNA damage
  • Comet assay
  • Heavy metal contamination