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IJSTR >> Volume 2- Issue 12, December 2013 Edition

International Journal of Scientific & Technology Research  
International Journal of Scientific & Technology Research

Website: http://www.ijstr.org

ISSN 2277-8616

Modulation Of Fumonisin B1 Toxic Action-Induced By Zeralenone In Human Intestinal Cells Caco-2

[Full Text]



Kouadio James Halbin, Moukha Serge, Brou Kouakou, Gnakri Dago



Index Terms: Fusarium-toxins, interactive-effect, caspace-3-kinetic-activity, cytotoxicity, oxidative-stress



Abstract: The natural co-occurrence of Fusarium toxins fumonisin B1 (FB1) and Zearalenone (ZEA) in cereal grains is well known. However, a few studies have been reported that address to the toxicity of Fusarium toxins mixtures. Thus, the aim of the present study was to investigate in the interactive effect of binary Fusarium toxins FB1 and ZEA on intestinal cells line Caco-2 using several cellular endpoints such as caspace-3 activity modulation, malonedialdehyde (MDA) production, lactate dehydrogenase (LDH) leakage as necrosis measure and cells viability as evaluated by lysosome and mitochondria integrities. As results, ZEA + FB1 led to an antagonistic effect on lysosome and mitochondria damage but, the necrosis-induced was more potent when compared to ZEA or FB1 alone showing an additive effect. Moreover, MDA production induced by ZEA+FB1 was higher than additive effect but not synergistic effect. At last, the combined effect of toxins on key apoptosis enzyme caspace-3 kinetic activity was an additive effect after 6 h and 24 h but, after 3h, ZEA tended to exert its anti-apoptotic action by reducing the enzyme activation by FB1. Taken together, the results were contrasted and results suggested that combined effects of binary Fusarium toxins ZEA and FB1 in cell line Caco-2 were unpredictable and varied according to several parameters such as the cellular endpoints and the duration of cells incubation with toxins.



[1] M.F. Dutton, “Fumonisins, mycotoxins of increasing importance: Their nature and their effects”, Pharmacology and Theorapeutics, vol. 70, no. 2, pp. 137–161, Oct. 1996.

[2] F.S. Chu and G.Y. Li, “Simultaneous occurrence of fumonisin B1 and other mycotoxins in moldy corn collected from the People’s Republic of China in regions with high incidences of esophageal cancer,” Applied and Environmental Microbiology, vol. 60, no. 3, pp. 847-852, Mar. 1994.

[3] J.P. Rheeder, W.F.O. Marasas, P.G. Thiel, E.W. Sydenham, G.S. Shephard and D.J. Van Schalkwyk, “Fusarium moniliforme and fumonisins in corn in relation to human oesophageal cancer in Transkei,” Phytopathology, vol. 82, no. 3, pp. 353-857, Jan. 1992.

[4] K. Hendricks “Fumonisins and neural tube defects in South Texas,” Epidemiology, vol. 10, no. 2, pp. 198-200, Mar. 1999.

[5] S.C. Bezuidenhout, W.C.A. Gelderblom, C.P. Gorst-Allman, R.M. Horak, W.F.O Marasas, G. Spiteller and R. Vleggaar R, “Structure elucidation of the fumonisins, mycotoxins from Fusarium moniliforme,” Journal of the Chemical Society, Chemical Communications, 11, pp. 743–745, 1988.

[6] K. Abado-Bécognée, T.A. Mobio, R. Ennamany, F. Fleurat-Lessart, W.T. Shier, F. Badria and E.E. Creppy, “Cytotoxicity of fumonisin B1/implication of lipid peroxidation and inhibition of protein and DNA syntheses,” Arch. Toxicol., vol. 72, no. 4, pp. 233–236, Mar. 1998.

[7] J.M. Soriano, L. Gonzalez and A.I. Catala, “Mechanism of action of sphingolipids and their metabolites in the toxicity of fumonisin B1,” Prog Lipid Res., vol. 44, 6, pp. 345-356, Nov. 2005.

[8] N.V. Gopee and R.P. Sharma, “The mycotoxin fumonisin B1 transiently activates nuclear factor-kappaB, tumor necrosis factor alpha and caspase 3 via protein kinase Calpha-dependent pathway in porcine renal epithelial cells,” Cell Biol Toxicol. vol. 20, no. 4, pp. 197-212, Jul. 2004.

[9] T.A. Mobio, E. Tavan, I. Baudrimont, R. Anane, M.R. Carratu, A. Sanni, M.F. Gbeassor, T.W. Shier, J.F. Narbonne and E.E. Creppy, “Comparative study of the toxic effects of fumonisin B1 in rat C6 glioma cells and p53-null mouse embryo fibroblasts,” Toxicology, vol. 183, no. 1-3, pp. 65–75, Feb. 2003.

[10] J.H. Kouadio, D.S. Dano, S. Moukha, T.H. Mobio and E.E. Creppy “Effets of combination of Fusarium mycotoxins (deoxynivalenol, zearalenone and fumonisin B1) on Caco-2 cells viability, inhibition of macromolecules syntheses, malonaldehyde level and DNA methylation and fragmentation,” Toxicon vol. 49, no. 3, pp. 306 - 317, Mar. 2007.

[11] A. Zinedine, J-M. Soriano, J.C. Molto and J. Man, “Review on the toxicity, occurrence, metabolism, detoxification, regulations and intake of zearalenone: an oestrogenic mycotoxin,” Food and Chemical Toxicology, vol. 45, no. 1, pp. 1–18, Jan. 2007.

[12] W.T. Shier, A.C. Shier, X. Xie and C.J. “Mirocha Structure–activity relationships for human oestrogenic activity in zearalenone mycotoxins,” Toxicon vol. 39, no. 9, pp. 1435–1438, Sep. 2001.

[13] J.H. Kouadio, T.H. Mobio, I. Baudrimont, S. Moukha, D.S. Dano and E.E. Creppy, “Comparative study of cytoxicity and oxidative stress induce by deoxynivalenol, zearalenone of fumonisin B1 in Human intestinal cell line Caco-2,”Toxicology, vol. 213, no 1-2, pp. 56-65, Feb. 2005.

[14] W. Hassen, I. Ayed-Boussema, A.A. Oscoz, A.C. Lopez and H. Bacha, “The role of oxidative stress in zearalenone-mediated toxicity in Hep G2 cells: oxidative DNA damage, gluthatione depletion and stress proteins induction,”Toxicology, vol. 232, no. 3, pp. 294–302, Apr. 2007.

[15] G.Y. Li and N.N. Osborne, “Oxidative-induced apoptosis to an immortalized ganglion cell line is caspase independent but involves the activation of poly (ADP-ribose) polymerase and apoptosis-inducing factor,” Brain Research, vol. 1188, pp. 35–43, Jan. 2008.

[16] L. Jia, Y.Y. Ji, S.L. Shin, O.S. Young, H.K. Dong, A.L. Seung, S. Xianglin and C.L. “Jeong, Cellular mechanisms of the cytotoxic effects of the zearalenone metabolites a-zearalenol and b-zearalenol on RAW264.7 macrophages,” Toxicology in Vitro, vol. 27, no. 3, pp. 1007–1017 , Apr. 2013.

[17] A.E. Desjardins, H.K. Manandhar, R.D. Plattner, G.G. Manandhar, S.M. Poling and C.M. Maragos, “Fusarium species from Nepalese rice and production of mycotoxins and gibberellic acid by selected species,” Applied and Environ-mental Microbiology, vol. 66, no. 3, pp. 1020-1025, Mar. 2000.

[18] B. Sangare-Tigori, S. Moukha, H.J. Kouadio, A.M. Betbeder, D.S. Dano and E.E. Creppy, “Co-occurrence of aflatoxin B1, fumonisin B1, ochratoxin A and zearalenone incereals and peanuts from Cote d'Ivoire” Food Addit Contam., vol. 23, no. 10, pp. 1000-1007, Oct. 2006.

[19] M. Rousset, M. Laburthe, M. Pinto, G. Chevalier, C. Rouyer-Fessard, E. Dussaulx, G. Trugnan, N. Boige, J.L. Brun and A. Zweibaum, “Enterocytic differentiation and glucose utilisation in the human colon tumour cell line Caco-2: modulation by forskolin,” J. Cell. Physiol., vol. 123, no. 3, pp. 377–385, Jun. 1985.

[20] A. Yusup , H. Upur , I. Baudrimont, A. Umar , T. Kader , B. Begaud , E.E. Creppy , and N. Moore, “Cytotoxicity of abnormal Savda Munziq aqueous extract in human hepatoma (HepG2) cells,” Fundam Clin Pharmacol., vol. 19, no. 4, pp. 465-472, Aug. 2005.

[21] M.M. Bradford, “A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding,”Analytical Biochemistry, vol. 72, pp. 248–254, May 1976.

[22] S.C. Gad and CS. Neil, Statistic Pharmaceutical analysis. Pharm Biomed Anal, vol. 33, no. , pp. 7-20, 2003.

[23] G. Fotakis and J.A. Timbrell, “In vitro cytotoxicity assays: Comparison of LDH, neutral red, MTT and protein assay in hepatoma cell lines following exposure to cadmium chloride,” Toxicology Letters, vol. 160, no. 2, pp. 171–177, Aug. 2006.

[24] L. Galluzzi, S.A. Aaronson, J. Abrams, E.S. Alnemri and D.W. Andrews, “Guidelines for the use and interpretation of assays for monitoring cell death in higher eukaryotes,” Cell Death Differ, vol. 16 no. 8, pp. 1093–1107, Aug. 2009.

[25] H. Babich and F. Borenfreund, “Fathead minnow FHM cells for use in in vitro cytotoxicity assays of aquatic pollutants,” Ecotoxicol Environ Saf., vol. 14, no. 1, pp. 78-87, Aug. 1987.

[26] B.E. Loveland, T.G. Jonhs, I.R. Mackay, F. Vaillant, Z.X. Wang and P.J. Hertzog, “Validation of the MTT dye assay for enumeration of cells in proliferative and antiproliferative assays,” Biochem. Int., vol. 27, no. 3, pp. 501-510, Jul. 1992.

[27] S.M. Smith, M.B. Wunder, D.A. Norris and Y.A. Shellman Simple Protocol for Using a LDH-Based Cytotoxicity Assay to Assess the Effects of Death and Growth Inhibition at the Same Time. PLoS ONE vol. 6, no. 11, pp. e26908, Nov. 2011.

[28] A.H. Wyllie, J.F. Kerr and A.R. Currie, “Cell death: the significance of apoptosis,” International Review of Cytology, vol. 68, pp. 251–306, 1980.

[29] L.S. Boeira, J.H. Bryce, G.G. Stewart and B. Flannigan, “The effect of combinations of Fusarium mycotoxins (deoxynivalenol, zearalenon and fumonisin B1) on growth of brewing yeasts,” J. Appl. Microbiol., vol.88, no. 3, pp. 388–403, Mar. 2000.

[30] A. Di Pietro, E.G. Vries, J.A. Gietema, D.C. Spierings and S. De Jong, “Testicular germ cell tumours: the paradigm of chemo-sensitive solid tumours, Review,” Int J Biochem Cell Biol. vol. 37, no. 12, pp. 2437-2456, Dec. 2005.

[31] J.Y. Yu, Z.H. Zheng, Y.O. Son, X. Shib, Y.O. Jang and J.C. Lee, “Mycotoxin zearalenone induces AIF- and ROS-mediated cell death through p53- and MAPK-dependent signaling pathways in RAW264.7 macrophages,” Toxicology in Vitro, vol. 25, no. 8, pp. 1654–1663, Dec. 2011.