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Fusarik Asit ve Enniatin-A Mikotoksinlerinin İnsan Umblikal Ven Endotel Hücreleri (HUVEC) Üzerine Sitotoksik Etkilerinin Değerlendirilmesi

Year 2018, Volume: 22 Issue: Special, 133 - 140, 05.10.2018

Sevcan Mamur

Abstract

Fusarik asit (FA) ve Enniatin-A (EN-A) Fusarium spp. cinsi mikotoksinler olup gıdaları ve yemleri kontamine edebilirler. Tahıllarda mikotoksin varlığı önemli sağlık sorunlarına yol açmakla birlikte ekonomik kayıplara da sebep olmaktadır. Bu çalışmada FA ve EN-A’nın potansiyel sitotoksik etkileri insan umblikal ven endotel (HUVEC) hücre hattında 3-(4,5-dimethylthiazolyl-2)-2,5 diphenyltetrazolium bromid (MTT) testi ile incelenmiştir. Her iki mikotoksinin de farklı konsantrasyonları (FA için 0.78, 1.56, 3.125, 6.25, 12.5, 25, 50, 100, 150, 200, 400 µg/mL, EN-A için 0.048, 0.098, 0.195, 0.39, 0.78, 1.56, 3.125, 6.25 µg/mL) 24 ve 48 saat muamele sürelerinde uygulanmıştır. Sonuç olarak, FA ve EN-A’nın hücre canlılığını (%), her iki muamele süresinde de yüksek konsantrasyonlarda önemli düzeyde düşürdüğü belirlenmiştir. FA’nın 24 saatlik uygulamasında IC50 (hücrelerin %50’sini öldüren) değerinin 150 μg/mL olduğu, 48 saatlik uygulamasında ise 200 μg/mL olduğu tespit edilmiştir. EN-A’nın ise IC50 değerinin 24 saatlik uygulamada 3.125 μg/mL, 48 saatlik uygulamada ise 1.56 μg/mL olduğu saptanmıştır. Bu sonuçlara göre FA ve EN-A’nın yüksek konsantrasyonlarda HUVEC hücrelerinde sitotoksik etki gösterdikleri gözlenmiştir. Ayrıca, EN-A mikotoksininin FA’dan daha fazla toksik etkiye sahip olduğu söylenebilir. Bu sitotoksik etki, hücre döngüsünde ve hücre proliferasyonunda yavaşlamaya  dolayısıyla DNA replikasyonun bozulmasına ve hücrelerde apoptozise neden olabilir.

Keywords

Fusarik asit Enniatin-A; Mikotoksin; HUVEC hücre hattı; MTT testi

References

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Year 2018, Volume: 22 Issue: Special, 133 - 140, 05.10.2018

Sevcan Mamur

Abstract

References

  • [1] Loi, M., Fanelli, F., Liuzzi, V.C., Logrieco, A.F., Mulè, G. 2017. Mycotoxin Biotransformation by Native and Commercial Enzymes: Present and Future Perspectives. Toxins, 9, 111.
  • [2] Patriarca, A., Pinto, V.F. 2017. Prevalence of mycotoxins in foods and decontamination. Current Opinion in Food Science, 14, 50–60.
  • [3] Aksoy, H., Yılmaz, S., Çelik, M., Yüzbaşıoğlu, D., Ünal, F. 2008-II. Moniliformin Mikotoksininin In Vitro Genotoksik Etkileri. SAÜ Fen Edebiyat Dergisi, 1-14.
  • [4] Oruç, H.H. 2005. Mikotoksinler ve Tanı Yöntemleri. Uludağ Üniversitesi Veteriner Fakültesi Dergisi, 24, 1-2-3-4, 105-110.
  • [5] Solhaug, A., Karlsøen, L.M., Holme, J.A., Kristoffersen, A.B., Eriksen, G.S. 2016. Immunomodulatory effects of individual and combined mycotoxins in the THP-1 cell line. Toxicology in Vitro, 36, 120–132.
  • [6] Nguyen, P.A., Strub, C., Fontana, A., Schorr-Galindo, S. 2017. Crop molds and mycotoxins: Alternative management using biocontrol. Biological Control 104, 10–27.
  • [7] Öksüztepe, G., Erkan, S. 2016. Mikotoksinler ve Halk Sağlığı Açısından Önemi. Harran Üniversitesi Veteriner Fakültesi Dergisi, 5(2), 190-195.
  • [8] Rocha, M.E.B., Freire, F.D.C.O., Maia, F.E.F., Guedes, M.I.F., Rondina, D. 2014. Mycotoxins and their effects on human and animal health. Food Control, 36(1), 159-165, 2014.
  • [9] Stanciu, O., Juan, C., Miere, D., Loghin, F., Manes, J. 2017. Occurrence and co-occurrence of Fusarium mycotoxins in wheat grains and wheat flour from Romania. Food Control, 73, 147-155, 2017.
  • [10] Scott, P.M. 2004. Other mycotoxins, Mycotoxins in Food - Detection and Control. Editors: Magan N., Olsen M. Cambridge, CRC Press, Woodhead Publishing Ltd., 406-427.
  • [11] Springler, A. Vrubel, G.J., Mayer, E., Schatzmayr, G., Novak, B. 2016. Effect of Fusarium-Derived Metabolites on the Barrier Integrity of Differentiated Intestinal Porcine Epithelial Cells (IPEC-J2). Toxins, 8, 345.
  • [12] Stankovic, S., Levic, J., Petrovic, T., Logrieco, A., Moretti, A. 2007. Pathogenicity and mycotoxin production by Fusarium proliferatum isolated from onion and garlic in Serbia. European Journal of Plant Pathology, 118 (2), 165-172.
  • [13] Smith, T.K. 1992. Recent advances in the understanding of Fusarium trichothecene mycotoxicoses. Journal of Animal Science, 70 (12), 3989-3993.
  • [14] Voss, K.A., Porter, J. K., Bacon, C.W., Meredith, F. I., Norred, W.P., 1999. Fusaric acid and modification of the subchronic toxicity to rats of fumonisins in F. moniliforme culture material”, Food and Chemical Toxicology, 37, 853-861.
  • [15] Yabuta, T., Kambe, K. Hayashi, T. 1937. Biochemistry of the bakanaefungus. I. Fusarinic acid, a new product of the bakanae fungus. Journal of the Agricultural Chemical Society of Japan, 10, 1059-1068.
  • [16] Abdul, N.S., Nagiah, S., Chuturgoon, A.A. 2016. Fusaric acid induces mitochondrial stress in human hepatocellular carcinoma (HepG2) cells. Toxicon, 119, 336-344.
  • [17] Fornelli, F., Minervini, F., Logrieco, A. 2004. Cytotoxicity of fungal metabolites to lepidopteran (Spodoptera frugiperda) cell line (SF 9). Journal of Invertebrate Pathology, 85, 74-79.
  • [18] Behm, C., Degen, G.H., Follmann, W. 2009. The Fusarium toxin enniatin B exerts no genotoxic activity, but pronounced cytotoxicity in vitro. Molecular Nutrition&Food Research, 53, 423-430.
  • [19] Tonshin, A.A., Teplova, V.V., Andersson, M.A., Salkinoja-Salonen, M.S. 2010. The Fusarium mycotoxins enniatins and beauvericin cause mitochondrial dysfunction by affecting the mitochondrial volume regulation, oxidative phosphorylation and ion homeostasis. Toxicology, 276, 49-57.
  • [20] Ivanova, L., Skjerve, E., Eriksen, G.S., Uhling, S. 2006. Cytotoxicity of enniatins A, A1, B, B1, B2 and B3 from Fusarium avenaceum. Toxicon, 47, 868-876.
  • [21] Dornetshuber, R., Heffeter, P., Kamyar, M.R., Peterbauer, T., Berger, W., Lemmens-Gruber, R. 2007. Enniatin exerts p53-dependent cytostatic and p53-independent cytotoxic activities against human cancer cells. Chemical Research in Toxicology, 20, 465-473.
  • [22] Watjen, W., Debbab, A., Hohlfeld, A., Chovolou, Y., Kampkötter, A., Edrada, R.A., Ebel, R., Hakiki, A., Mosaddak, M., Totzke, F., Kubbutat, M., Proksch, P. 2009. Enniatins A1, B and B1 from an endophytic strain of Fusarium tricintum induce apoptotic cell death in H4IIE hepatoma cells accompanied by inhibition of ERK phosphorylation. Molecular Nutrition&Food Research, 53, 431-440.
  • [23] Vesonder, R.F., Gasdorf, H., Peterson, R.E. 1993. Comparison of the cytotoxicities of Fusarium metabolites and Alternaria metabolite AAL-toxin to cultured mammalian cell lines. Archives of Environmental Contamination and Toxicology, 24 (4), 473-477.
  • [24] Fernandez-Pol, J.A., Klos, D.J., Hamilton, P.D. 1993. Cytotoxic activity of fusaric acid on human adenocarcinoma cells in tissue culture” Anticancer Research, 13(1), 57-64.
  • [25] Meca, G., Font, G., Ruiz, M.J. 2011. Comparative cytotoxicity study of enniatins A, A1, A2, B, B1, B4 and J3 on Caco-2 cells, Hep-G 2 and HT-29. Food and Chemical Toxicology, 49(9), 2464-2469.
  • [26] Lu, H., Fernández-Franzón, M., Font, G., Ruiz, M.J. 2013. Toxicity evaluation of individual and mixed enniatins using an in vitro method with CHO-K1 cells. Toxicology In Vitro, 27, 672-680.
  • [27] Yazır, Y. 2004. İnsan umbilikal venlerinden elde edilen endotel hücre kültüründe, vasküler endoteliyal büyüme faktörünün, vasküler hücre adezyon molekülü-1 ve intersellüler adezyon molekülü-1 ekspresyonu üzerine etkilerinin incelenmesi. KOÜ Sağlık Bilimleri Enstitüsü, Kocaeli, Doktora Tezi.
  • [28] Yazır, Y., Dalçık, H., 2012. Vasküler Patolojilerin Araştırılmasında Önemli Bir Araç: Endotel Hücre Kültürü. Koşuyolu Kalp Dergisi, 15(3),137-142.
  • [29] Riss, T.L., Moravec, R.A., Niles, A.L., Duellman, S., Benink, H.A., Worzella, T.J., Minor, L. 2016. Cell Viability Assays. Assay Guidance Manual, 1-31.
  • [30] https://www.sigmaaldrich.com/Graphics/COfAInfo/SigmaSAPQM/SPEC/F6/F6513/F6513BULK________SIGMA____.pdf (Erişim Tarihi: 29.04.2018).
  • [31] https://www.scbt.com/scbt/product/enniatin-a-2503-13-1. (Erişim Tarihi: 07.05.2018).
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  • [33] Ruyck, K.D., Boevre, M.D. Huybrechts, I., Saeger, S.D. 2015. Dietary mycotoxins, co-exposure, and carcinogenesis in humans: Short review. Mutation Research/Reviews in Mutation Research, 766, 32-41.
  • [34] Commission Regulation 2006/1881/EC of 19 December 2006 Setting Maximum Levels for Certain Contaminants in Food stuffs. Available online: http://eurlex.europa.eu/legalcontent/EN/TXT/PDF/?uri=CELEX:32006R1881&from=en (accessed on 03 November 2016).
  • [35] Uzun, İ. H., Bayındır, F. 2011. Dental materyallerin biyouyumluluk test yöntemleri. Gazi Üniversitesi Diş Hekimliği Fakültesi Dergisi, 28(2), 115-22.
  • [36] Slater, T.F., Sawyer, B. Straeuli, U. 1963. Studies on succınate-tetrazolium reductase systems. III. Points of coupling of four different tetrazolium salts. Biochimica et Biophysica Acta, 77, 383-393.
  • [37] Fotakis, G., Timbrell, J.A. 2006. In vitro cytotoxicity assays: comparison of LDH, neutral red, MTT and protein assay in hepatoma cell lines following exposure to cadmium chloride. Toxicology Letters, 160(2), 171-177.
  • [38] Berek, L., Petri, I.B., Mesterhazy, A., Téren, J., Molnár, J. 2001. Effects of mycotoxins on human immune functions in vitro. Toxicology In Vitro, 15(1), 25-30.
  • [39] Stack, B.C., Md, F., Hansen, J.P., Ruda, J.M., Jaglowski, J., Shvidler, J., Hollenbeak, C.S. 2004. Fusaric acid: a novel agent and mechanism to treat HNSCC. Otolaryngol Head and Neck Surgery, 131, 54-60.
  • [40] Ogata, S., Inoue, K., Iwata, K., Okumura, K., Taguch, H. 2001. Apoptosis induced by picolinic acid-related compounds in HL-60 cells. Bioscience Biotechnology Biochemistry 65, 2337-233.
  • [41] Jaglowski, J.R., Stack B.C. 2006. Enhanced growth inhibition of squamous cell carcinoma of the head and neck by combination therapy of fusaric acid and paclitaxel or carboplatin. Cancer Letters, 243, 58-63.
  • [42] Ruda, J.M., Beus, K.S., Hollenbeak, C.S., Wilson, R.P., Stack, B.C. 2006. The effect of single agent oral fusaric acid (FA) on the growth of subcutaneously xenografted SCC-1 cells in a nude mouse model. Investigational New Drugs, 24, 377-381.
  • [43] Ye, J., Montero, M., Stack, B.C. 2013. Effects of fusaric acid treatment on HEp2 and docetaxel-resistant HEp2 laryngeal squamous cell carcinoma. Chemotherapy, 59, 121-128.
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There are 54 citations in total.

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Journal Section Articles
Authors

Sevcan Mamur

Publication Date October 5, 2018
Published in Issue Year 2018 Volume: 22 Issue: Special

Cite

APA Mamur, S. (2018). Fusarik Asit ve Enniatin-A Mikotoksinlerinin İnsan Umblikal Ven Endotel Hücreleri (HUVEC) Üzerine Sitotoksik Etkilerinin Değerlendirilmesi. Süleyman Demirel Üniversitesi Fen Bilimleri Enstitüsü Dergisi, 22, 133-140.
AMA Mamur S. Fusarik Asit ve Enniatin-A Mikotoksinlerinin İnsan Umblikal Ven Endotel Hücreleri (HUVEC) Üzerine Sitotoksik Etkilerinin Değerlendirilmesi. SDÜ Fen Bil Enst Der. October 2018;22:133-140.
Chicago Mamur, Sevcan. “Fusarik Asit Ve Enniatin-A Mikotoksinlerinin İnsan Umblikal Ven Endotel Hücreleri (HUVEC) Üzerine Sitotoksik Etkilerinin Değerlendirilmesi”. Süleyman Demirel Üniversitesi Fen Bilimleri Enstitüsü Dergisi 22, October (October 2018): 133-40.
EndNote Mamur S (October 1, 2018) Fusarik Asit ve Enniatin-A Mikotoksinlerinin İnsan Umblikal Ven Endotel Hücreleri (HUVEC) Üzerine Sitotoksik Etkilerinin Değerlendirilmesi. Süleyman Demirel Üniversitesi Fen Bilimleri Enstitüsü Dergisi 22 133–140.
IEEE S. Mamur, “Fusarik Asit ve Enniatin-A Mikotoksinlerinin İnsan Umblikal Ven Endotel Hücreleri (HUVEC) Üzerine Sitotoksik Etkilerinin Değerlendirilmesi”, SDÜ Fen Bil Enst Der, vol. 22, pp. 133–140, 2018.
ISNAD Mamur, Sevcan. “Fusarik Asit Ve Enniatin-A Mikotoksinlerinin İnsan Umblikal Ven Endotel Hücreleri (HUVEC) Üzerine Sitotoksik Etkilerinin Değerlendirilmesi”. Süleyman Demirel Üniversitesi Fen Bilimleri Enstitüsü Dergisi 22 (October 2018), 133-140.
JAMA Mamur S. Fusarik Asit ve Enniatin-A Mikotoksinlerinin İnsan Umblikal Ven Endotel Hücreleri (HUVEC) Üzerine Sitotoksik Etkilerinin Değerlendirilmesi. SDÜ Fen Bil Enst Der. 2018;22:133–140.
MLA Mamur, Sevcan. “Fusarik Asit Ve Enniatin-A Mikotoksinlerinin İnsan Umblikal Ven Endotel Hücreleri (HUVEC) Üzerine Sitotoksik Etkilerinin Değerlendirilmesi”. Süleyman Demirel Üniversitesi Fen Bilimleri Enstitüsü Dergisi, vol. 22, 2018, pp. 133-40.
Vancouver Mamur S. Fusarik Asit ve Enniatin-A Mikotoksinlerinin İnsan Umblikal Ven Endotel Hücreleri (HUVEC) Üzerine Sitotoksik Etkilerinin Değerlendirilmesi. SDÜ Fen Bil Enst Der. 2018;22:133-40.
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