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Protective effects of antioxidants on deoxynivalenol-induced damage in murine lymphoma cells

Mycotoxin Research volume 29, pages 203–208 (2013)Cite this article

Abstract

As contradictory results have been reported on the immunotoxic properties of deoxynivalenol (DON) in animal studies, we introduced a lymphoblast cell culture model in order to examine the effects of DON on lymphoblastic cell growth and metabolism as well as the preventive properties of free radical scavenger molecules against the DON-induced cell damage. Murine YAC-1 lymphoma cells were used because lymphoblasts have been shown to be sensitive to DON-induced immunotoxicity. Cells were quantified and their proliferative activity was measured by a proliferation test. Lipid peroxidation and protein oxidation were determined using assays quantifying thiobarbituric acid reactive substances (TBARS) and carbonylated proteins. Severely reduced cell counts were detected in DON-treated samples, confirmed by a 5–10 times lower proliferative activity. Significant increases in lipid peroxidation and protein oxidation were found in parallel incubated samples. The pre-incubation with free radical scavengers significantly reduced DON-induced changes to proteins and lipids as well as the tarnished cell viability and cell proliferation. These results suggest that YAC-1 lymphoma cells are a suitable model to investigate and elucidate the basic molecular and cellular mechanisms for possible immunotoxic effects of DON. With regard to the impact of free radical scavengers, the applied in-vitro model might enable the investigation of potential prophylactic and therapeutic effects before or even without harmful animal experiments and cost- and time-intensive expenses.

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References

  • Abraham R, Lester P (1994) Oxidative damage to proteins: Spectrophotometric method for carbonyl assy. Methods Enzymol 357–363

  • Berek L, Petri IB, Mesterházy A, Téren J, Molnár J (2001) Effects of mycotoxins on human immune functions in vitro. Toxicol In Vitro 15(1):25–30

    PubMed  Article  CAS  Google Scholar 

  • Bondy GS, Pestka JJ (2000) Immunomodulation by fungaltoxin. J Toxicol Environ Health B 3:109–143

    Google Scholar 

  • Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    PubMed  Article  CAS  Google Scholar 

  • Casteel M, Nielsen C, Didier A, Dietrich R, Märtlbauer E (2010) Induction of MAPK-dependent transcription factors by deoxynivalenol in human cell lines. Mycotox Res 26:9–14

    Article  CAS  Google Scholar 

  • Costa S, Utan A, Cervellati R, Speroni E, Guerra MC (2007a) Catechins: natural free-radical scavengers against ochratoxin A-induced cell damage in a pig kidney cell line (LLC-PK1). Food Chem Toxicol 45(10):1910–1917

    PubMed  Article  CAS  Google Scholar 

  • Costa S, Utan A, Speroni E, Cervellati R, Piva G, Prandini A, Guerra MC (2007b) Carnosic acid from rosemary extracts: a potential chemoprotective agent against aflatoxin B1. An in vitro study. J Appl Toxicol 27(2):152–159

    PubMed  Article  CAS  Google Scholar 

  • Costa S, Schwaiger S, Cervellati R, Stuppner H, Speronia E, Guerra MC (2009) In vitro evaluation of the chemoprotective action mechanisms of leontopodic acid against aflatoxin B1 and deoxynivalenolinduced cell damage. J Appl Toxicol 29:7–14

    PubMed  Article  CAS  Google Scholar 

  • Fagan JM, Sleczka BG, Sohar I (1999) Quantitation of oxidative damage to tissue proteins. Int J Biochem Cell Biol 31(7):751–757

    PubMed  Article  CAS  Google Scholar 

  • Froquet R, Arnold F, Batina P, Parent-Massin D (2003) Do trichothecenes reduce viability of circulating blood cells and modify haemostasis parameters? Mycopathologia 156(4):349–356

    PubMed  Article  CAS  Google Scholar 

  • Guerra MC, Galvano F, Bonsi L, Speroni E, Costa S, Renzulli C, Cervellati R (2005) Cyanidin-3-O-beta-glucopyranoside, a natural free-radical scavenger against aflatoxin B1- and ochratoxin a-induced cell damage in a human hepatoma cell line (Hep G2) and a human colonic adenocarcinoma cell line (CaCo-2). Br J Nutr 94(2):211–220

    PubMed  Article  CAS  Google Scholar 

  • Karppanen E, Rizzo A, Saari L, Berg S, Boström H (1989) Investigation on trichothecene-stimulated lipid peroxidation and toxic effects of trichothecenes in animals. Acta Vet Scand 30(4):391–399

    PubMed  CAS  Google Scholar 

  • Khol-Parisini A, Hellweg P, Razzazi-Fazeli E, Saalmüller A, Strasser A, Tichy A, Zentek J (2012) Highly deoxynivalenol contaminated oats does not affect cellular or humoral immune parameters in horses. Arch Anim Nutr 66(2):149–161

    PubMed  Article  CAS  Google Scholar 

  • Kouadio JH, Mobio TA, Baudrimont I, Moukha S, Dano SD, Creppy EE (2005) Comparative study of cytotoxicity and oxidative stress induced by deoxynivalenol, zearalenone or fumonisin B1 in human intestinal cell line Caco-2. Toxicology 213(1–2):56–65

    PubMed  Article  CAS  Google Scholar 

  • Kouadio JH, Dano SD, Moukha S, Mobio TA, Creppy EE (2007) Effects of combinations of Fusarium mycotoxins on the inhibition of macromolecular synthesis, malondialdehyde levels, DNA methylation and fragmentation, and viability in Caco-2 cells. Toxicon 49(3):306–317

    PubMed  Article  CAS  Google Scholar 

  • Krishnaswamy R, Devaraj SN, Padma VV (2010) Lutein protects HT-29 cells against deoxynivalenol-induced oxidative stress and apoptosis: prevention of NF-kappaB nuclear localization and down regulation of NF-kappaB and cyclo-oxygenase-2 expression. Free Radic Biol Med 49(1):50–60

    PubMed  Article  CAS  Google Scholar 

  • Le Dréan G, Auffret M, Batina P, Arnold F, Sibiril Y, Arzur D, Parent-Massin D (2005) Myelotoxicity of trichothecenes and apoptosis: an in vitro study on human cord blood CD34+ hematopoietic progenitor. Toxicol In Vitro 19(8):1015–1024

    PubMed  Article  Google Scholar 

  • Luongo D, De Luna R, Russo R, Severino L (2008) Effects of four Fusarium toxins (fumonisin B(1), alpha-zearalenol, nivalenol and deoxynivalenol) on porcine whole-blood cellular proliferation. Toxicon 52(1):156–162

    PubMed  Article  CAS  Google Scholar 

  • Møller IM, Rogowska-Wrzesinska A, Rao RS (2011) Protein carbonylation and metal-catalyzed protein oxidation in a cellular perspective. J Proteomics 74(11):2228–2242

    PubMed  Article  Google Scholar 

  • Nielsen C, Casteel M, Didier A, Dietrich R, Märtlbauer E (2009) Trichothecene-induced cytotoxicity on human cell lines. Mycotox Res 25:77–84

    Article  CAS  Google Scholar 

  • Parent-Massin D (2004) Haematotoxicity of trichothecenes. Toxicol Lett 153(1):75–81

    PubMed  Article  CAS  Google Scholar 

  • Pestka JJ (2010) Deoxynivalenol: mechanisms of action, human exposure, and toxicological relevance. Arch Toxicol 84:663–679

    PubMed  Article  CAS  Google Scholar 

  • Renzulli C, Galvano F, Pierdomenico L, Speroni E, Guerra MC (2004) Effects of rosmarinic acid against aflatoxin B1 and ochratoxin-A-induced cell damage in a human hepatoma cell line (Hep G2). J Appl Toxicol 24(4):289–296

    PubMed  Article  CAS  Google Scholar 

  • Rizzo AF, Atroshi F, Ahotupa M, Sankari S, Elovaara E (1994) Protective effect of antioxidants against free radical-mediated lipid peroxidation induced by DON or T-2 toxin. Zentralbl Veterinarmed A 41(2):81–90

    PubMed  CAS  Google Scholar 

  • Rotter BA, Prelusky DB, Pestka JJ (1996) Toxicology ofdeoxynivalenol vomitoxin. J Toxicol Environ Health 48:1–43

    Google Scholar 

  • Shank RA, Foroud NA, Hazendonk P, Eudes F, Blackwell BA (2011) Current and future experimental strategies for structural analysis of trichothecene mycotoxins–a prospectus. Toxins (Basel) 3(12):1518–1553

    Article  CAS  Google Scholar 

  • Sivanesan D, Begum VH (2007) Preventive role of Gynandropsis gynandra L., against aflatoxin B1 induced lipid peroxidation and antioxidant defense mechanism in rat. Indian J Exp Biol 45(3):299–303

    PubMed  CAS  Google Scholar 

  • Strasser A, Kühnel H, Velde K, Dadak AM (2012) Immunomodulation during and after castration under inhalation anaesthetic without genotoxic effects on equine lymphocytes. Res Vet Sci 92(2):306–310

    PubMed  Article  CAS  Google Scholar 

  • Taranu I, Marina DE, Burlacu R, Pinton P, Damian V, Oswald IP (2010) Comparative aspects of in vitro proliferation of human and porcine lymphocytes exposed to mycotoxins. Arch Anim Nutr 64(5):383–393

    PubMed  Article  CAS  Google Scholar 

  • Therond P (2006) Oxidative stress and damages to biomolecules (lipids, proteins, DNA). Ann Pharm Fr 64(6):383–389

    PubMed  Article  CAS  Google Scholar 

  • Uzarski RL, Islam Z, Pestka JJ (2003) Potentiation of trichothecene-induced leukocyte cytotoxicity and apoptosis by TNF-α and Fas activation. Chem Biol Interact 146:105–119

    PubMed  Article  CAS  Google Scholar 

  • Vincent AM, McLean LL, Backus C, Feldman EL (2005) Short-term hyperglycemia produces oxidative damage and apoptosis in neurons. FASEB J 19(6):638–640

    PubMed  CAS  Google Scholar 

  • Weber M, Stiller S, Balogh K, Wágner L, Erdélyi M, Mézes M (2007) Effect of feeding T-2 toxin contaminated feed on the utilisation of vitamin E in chickens. Acta Vet Hung 55(1):21–27

    PubMed  Article  CAS  Google Scholar 

  • Wong CM, Bansal G, Marcocci L, Suzuki YJ (2012) Proposed role of primary protein carbonylation in cell signaling. Redox Rep 17(2):90–94

    PubMed  Article  CAS  Google Scholar 

  • Yunus AW, Ghareeb K, Twaruzek M, Grajewski J, Böhm J (2012) Deoxynivalenol as a contaminant of broiler feed: effects on bird performance and response to common vaccines. Poult Sci 91(4):844–851

    PubMed  Article  CAS  Google Scholar 

  • Zhang X, Jiang L, Geng C, Cao J, Zhong L (2009) The role of oxidative stress in deoxynivalenol-induced DNA damage in HepG2 cells. Toxicon 54(4):513–518

    PubMed  Article  CAS  Google Scholar 

  • Zhou BJ, Li YH, Zhang XH, Xing LX, Yan X, Wang JL, Liu J, Xing X (2006) Effects of vitamin C on apoptosis and proliferation inhibition of human peripheral blood mononuclear cells induced by deoxynivalenol in vitro. Zhonghua Yu Fang Yi Xue Za Zhi 40(5):309–313

    PubMed  CAS  Google Scholar 

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Acknowledgment

The authors would like to express their gratitude to Georg Hofer for excellent technical assistance.

Conflict of interest

The authors certify that there is no conflict of interest with any financial organization regarding the material discussed in the manuscript.

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Affiliations

  1. Institute of Physiology, Pathophysiology and Biophysics, Department of Biomedical Sciences, University of Veterinary Medicine Vienna, Veterinaerplatz 1, 1210, Wien, Austria

    Alois Strasser & Mirja Carra

  2. Institute of Animal Nutrition and Functional Plant Compounds, University of Veterinary Medicine Vienna, Veterinaerplatz 1, 1210, Wien, Austria

    Khaled Ghareeb & Josef Böhm

  3. Clinic for Avian, Reptile and Fish Medicine, Department for Farm Animals and Veterinary Public Health, University of Veterinary Medicine Vienna, Veterinaerplatz 1, 1210, Wien, Austria

    Wageha Awad

Authors
  1. Alois Strasser
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  2. Mirja Carra
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  3. Khaled Ghareeb
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  4. Wageha Awad
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  5. Josef Böhm
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Corresponding author

Correspondence to Alois Strasser.

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Strasser, A., Carra, M., Ghareeb, K. et al. Protective effects of antioxidants on deoxynivalenol-induced damage in murine lymphoma cells. Mycotoxin Res 29, 203–208 (2013). https://doi.org/10.1007/s12550-013-0170-2

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  • DOI: https://doi.org/10.1007/s12550-013-0170-2

Keywords

  • Deoxynivalenol (DON)
  • Immunotoxicity
  • In vitro
  • Antioxidants
  • Prevention