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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

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.

References

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

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.
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  • [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.
  • [44] Iwahashi, H., Kawamori, H., Fukushima, K. 1999. Quinolinic acid, a-picolinic acid, fusaric acid, and 2,6-pyridinedicarboxylic acid enhance the Fenton reaction in phosphate buffer. Chemico-Biological Interactions, 118, 201-215.
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There are 54 citations in total.

Details

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. J. Nat. Appl. Sci. 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”, J. Nat. Appl. Sci., 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. J. Nat. Appl. Sci. 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. J. Nat. Appl. Sci. 2018;22:133-40.

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