, Volume 31, Issue 5, pp 845–858 | Cite as

Selenised yeast sources differ in their capacity to protect porcine jejunal epithelial cells from cadmium-induced toxicity and oxidised DNA damage

  • Sarah Lynch
  • Karina Horgan
  • Dermot Walls
  • Blánaid WhiteEmail author


In recent years there has been increasing interest in the use of selenised yeast (Se-Y) as an antioxidant feed supplement. Here, three selenised yeast products are differentiated in terms of bioefficiency and the ameliorative effect on Cadmium (Cd) toxicity in porcine epithelial cells. A porcine digestion in vitro model was chosen to more accurately simulate the bioavailability of different Se-Y preparations, allowing a comprehensive understanding of the bio efficiency of each Se-Y compound in the porcine model. To elucidate a possible mechanism of action of selenium a number of bioassays were applied. Levels of Se dependent antioxidant enzymes (glutathione peroxidase and thioredoxin reductase) were evaluated to analyze the ROS neutralizing capacity of each Se-Y compound. The effects of Se-Y sources on Cd-induced DNA damage and apoptosis-associated DNA fragmentation was assessed using comet and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays, respectively. Lesion-specific DNA damage analysis and in vitro DNA repair assay determined the DNA repair capacity of each Se-Y source. The results presented in this study confirm that the ability of different commercially available Se-Y preparations to enhance a range of cellular mechanisms that protect porcine gut epithelial cells from Cd-induced damage is concentration-dependent and illustrates the difference in bioefficiency of different Se-Y compounds.


Selenium yeast Cadmium Comet assay TUNEL 



BW and DW are members of EU COST Action CA15132.

Compliance with ethical standards

Conflict of interest

Karina Horgan is an employee of Alltech Ltd. who retail selenium-enriched yeast as a commercial feed additive. Sarah Lynch is the recipient of a postgraduate studentship from Alltech Ltd.


  1. Arnaudguilhem C, Bierla K, Ouerdane L, Preud H, Yiannikouris A, Lobinski R (2012) Selenium metabolomics in yeast using complementary reversed-phase/hydrophilic ion interaction (HILIC) liquid chromatography—electrospray hybrid quadrupole trap/Orbitrap mass spectrometry. Anal Chim Acta 757:26–38. CrossRefPubMedGoogle Scholar
  2. Azqueta A, Collins AR (2013) The essential comet assay: a comprehensive guide to measuring DNA damage and repair. Arch Toxicol 87:949–968. CrossRefPubMedGoogle Scholar
  3. Azqueta A, Slyskova J, Langie SA, O’Neill Gaivão I, Collins AR (2014) Comet assay to measure DNA repair: approach and applications. Front Genet 5:288. CrossRefPubMedPubMedCentralGoogle Scholar
  4. Barger JL, Kayo T, Pugh TD, Vann J, Power R, Dawson K, Weindruch R, Prolla T (2012) Gene expression profiling reveals differential effects of sodium selenite, selenomethionine, and yeast-derived selenium in the mouse. Genes Nutr 7:55–165. CrossRefGoogle Scholar
  5. Bertin G, Averbeck D (2006) Cadmium: cellular effects, modifications of biomolecules, modulation of DNA repair and genotoxic consequences (a review). Biochimie 88(11):1549–1559. CrossRefPubMedGoogle Scholar
  6. Bierla K, Szpunar J, Yiannikouris A, Lobinski R (2012) Comprehensive speciation of selenium in selenium-rich yeast. Trends Anal Chem 41:122–132. CrossRefGoogle Scholar
  7. Boisen S, Fernhdez JA (1997) Prediction of the total tract digestibility of energy in feedstuffs and pig diets by in vitro analyses. Anim Feed Sci Technol 8401(97):277–286CrossRefGoogle Scholar
  8. Collins AR, Duthie S, Dobson V (1993) Direct enzymatic detection of endogenous oxidative base damage in human lymphocyte DNA. Carcinogenesis 14:733–1735CrossRefGoogle Scholar
  9. Collins AR, Ai-guo M, Duthie SJ (1995) The kinetics of repair of oxidative DNA damage (strand breaks and oxidised pyrimidines) in human cells. Mutat Res 336:69–77. CrossRefPubMedGoogle Scholar
  10. Collins AR, Dusinská M, Horváthová E, Munro E, Savio M, Stĕtina R (2001) Inter-individual differences in repair of DNA base oxidation, measured in vitro with the comet assay. Mutagenesis 16(4):297–301. CrossRefPubMedGoogle Scholar
  11. de Rosa V, Erkekoğlu P, Forestier A, Favier A, Hincal F, Diamond AM, Douki T, Rachidi W (2012) Low doses of selenium specifically stimulate the repair of oxidative DNA damage in LNCap prostate cancer cells. Free Radic Res 46:105–116. CrossRefPubMedGoogle Scholar
  12. Demirci A, Cox DJ (1999) Enhanced organically bound selenium yeast production by fed-batch fermentation. J Agri Food Chem 47(6):2496–2500. CrossRefGoogle Scholar
  13. 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(3–4):507–514. CrossRefPubMedGoogle Scholar
  14. EFSA (2011) Scientific opinion on safety and efficacy of Sel-Plex ® (organic form of selenium produced by Saccharomyces cerevisiae CNCM I-3060) for all species. EFSA J 9:1–52. CrossRefGoogle Scholar
  15. EFSA (2013) Scientific opinion on the safety and efficacy of l-selenomethionine as feed additive for all animal species 1. EFSA J 11(5):1–18. CrossRefGoogle Scholar
  16. Esmaeili S, Khosravi-Darani K, Pourahmad R, Komeili R (2012) An experimental design for production of selenium-enriched yeast. World Appl Sci J 19(1):31–37. CrossRefGoogle Scholar
  17. Fagan S, Owens R, Ward P, Connolly C, Doyle S, Murphy R (2015) Biochemical comparison of commercial selenium yeast preparations. Biol Trace Elem Res 166(1):245–259. CrossRefPubMedGoogle Scholar
  18. Fischer JL, Lancia JK, Mathur A, Smith ML (2006) Selenium protection from DNA damage involves a Ref1/p53/Brca1 protein complex. Anticancer Res 904(26):899–904Google Scholar
  19. Galbraith ML, Vorachek WR, Estill CT, Whanger PD, Bobe G, Davis TZ, Hall JA (2015) Rumen microorganisms decrease bioavailability of inorganic selenium supplements. Bio Trace Elem Res 171:338–343. CrossRefGoogle Scholar
  20. 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. CrossRefPubMedPubMedCentralGoogle Scholar
  21. Gyori BM, Venkatachalam G, Thiagarajan PS, Hsu D, Clement MV (2014) OpenComet: an automated tool for comet assay image analysis. Redox Biol 2:457–465. CrossRefPubMedPubMedCentralGoogle Scholar
  22. Hart WE, Marczak SP, Kneller AR, French RA, Morris DL Jr (2013) The abilities of selenium dioxide and selenite ion to coordinate DNA-bound metal ions and decrease oxidative DNA damage. J Inorg Biochem 125:1–8. CrossRefPubMedGoogle Scholar
  23. Hefnawy A, Tortora-Perez J (2010) The importance of selenium and the effects of its deficiency in animal health. Small Rumin Res 89:185–192. CrossRefGoogle Scholar
  24. Jung HJ, Kim HL, Kim YJ, Weon JI, Seo YR (2013) A novel chemopreventive mechanism of selenomethionine: enhancement of APE1 enzyme activity via a Gadd45a, PCNA and APE1 protein complex that regulates p53-mediated base excision repair. Oncol Rep 4(30):1581–1586. CrossRefGoogle Scholar
  25. Khera A, Vanderlelie JJ, Holland O, Perkins AV (2017) Overexpression of endogenous anti-oxidants with selenium supplementation protects trophoblast cells from reactive oxygen species-induced apoptosis in a Bcl-2-dependent manner. Biol Trace Elem Res 177(2):394–403. CrossRefPubMedGoogle Scholar
  26. Kieliszek M, Błażejak S, Płaczek M (2016) Spectrophotometric evaluation of selenium binding by Saccharomyces cerevisiae ATCC MYA-2200 and Candida utilis ATCC 9950 yeast. J Trace Elem Med Biol 35:90–96. CrossRefPubMedGoogle Scholar
  27. Langie SA, Cameron KM, Waldron KJ, Fletcher KP, von Zglinicki T, Mathers JC (2011) Measuring DNA repair incision activity of mouse tissue extracts towards singlet oxygen-induced DNA damage: a comet-based in vitro repair assay. Mutagenesis 26(3):461–471. CrossRefPubMedGoogle Scholar
  28. Letavayova L, Vlckova V, Brozmanova J (2006) Selenium: from cancer prevention to DNA damage. Toxicology 227:1–14. CrossRefPubMedGoogle Scholar
  29. Lynch SJ, Horgan KA, White B, Walls D (2016) 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. CrossRefPubMedGoogle Scholar
  30. Mahima Verma AK, Kumar A, Rahal A, Kumar V, Roy D (2012) Inorganic versus organic selenium supplementation: a review. Pak J Biol Sci 15:418–425. CrossRefPubMedGoogle Scholar
  31. McKelvey SM, Horgan K, Murphy R (2014) Chemical form of selenium differentially influences DNA repair pathways following exposure to lead nitrate. J Trace Elem Med Biol 29:151–169. CrossRefPubMedGoogle Scholar
  32. Meunier JP, Manzanilla EG, Anguita M, Denis S, Pérez JF, Gasa J, Cardot J, Moll X, Alric M (2008) Evaluation of a dynamic in vitro model to simulate the porcine ileal digestion of diets differing in carbohydrate composition. J Anim Sci 86:1156–1163. CrossRefPubMedGoogle Scholar
  33. Murphy R (2013) Understanding different types of organic selenium. Feedstuffs 85(52):31–33Google Scholar
  34. Oraby MM, Allababidy T, Ramadan EM (2015) The bioavailability of selenium in Saccharomyces cerevisiae. Ann Agric Sci 60(2):307–315. CrossRefGoogle Scholar
  35. Perucchietti P, Litjens W (2012) Why check selenomethionine levels in selenium yeast? Allaboutfeed 20(6):12Google Scholar
  36. Rayman MP (2004) The use of high-selenium yeast to raise selenium status: how does it measure up? Brit J Nutr 92(4):557–573. CrossRefPubMedGoogle Scholar
  37. Reyes LH, Encinar JR, Marchante-Gayón JM, Alonso JI, Sanz-Medel A (2006) Selenium bioaccessibility assessment in selenized yeast after “in vitro” gastrointestinal digestion using two-dimensional chromatography and mass spectrometry. J Chromatogr A 1110:108–116. CrossRefPubMedGoogle Scholar
  38. Rusetskaya NY, Borodulin VB (2015) Biological activity of organoselenium compounds in heavy metal intoxication. Biochem (Moscow) Suppl Ser B 9(1):45–57. CrossRefGoogle Scholar
  39. 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(3):293–305. CrossRefPubMedGoogle Scholar
  40. Seo YR, Sweeney C, Smith ML (2002) Selenomethionine induction of DNA repair response in human fibroblasts. Oncogene 21:3662–3669. CrossRefGoogle Scholar
  41. Srikanth RV, Van de Wiele T, Pratti VL, Tack F, Du 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. CrossRefGoogle Scholar
  42. Yoshida M, Fukunaga K, Tsuchita H, Yasumoto K (1999) An evaluation of the bioavailability of selenium in high-selenium yeast. J Nutr Sci Vitaminol 45:119–128CrossRefPubMedGoogle Scholar
  43. 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(11):e79643. CrossRefPubMedPubMedCentralGoogle Scholar
  44. Zeng H, Combs GF (2008) Selenium as an anticancer nutrient: roles in cell proliferation and tumor cell invasion. J Nutr Biochem 19(1):1–7. CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.School of BiotechnologyDublin City UniversityDublin 9Ireland
  2. 2.Alltech Biotechnology CentreDunboyneIreland
  3. 3.School of Chemical SciencesDublin City UniversityDublin 9Ireland

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