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Fumonisin B1: A Neurotoxic Mycotoxin / Fumonizin B1: Neurotoksični Mikotoksin

Ana-Marija Domijan
  • Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovačića 1, 10 000 Zagreb, Croatia
  • :
Published Online: 2013-01-16 | DOI: https://doi.org/10.2478/10004-1254-63-2012-2239

Abstract

Fumonisin B1 (FB1) is a mycotoxin produced by Fusarium spp. moulds that contaminate crop, predominantly maize, all around the world. More than 15 types of fumonisins have been indentified so far, but FB1 is the most abundant and toxicologically the most significant one. FB1 has a wide range of toxic effects, depending on animal species. In horses FB1 causes equine leukoencephalomalacia (ELEM), in pigs pulmonary oedema and in experimental rodents nephrotoxicity and hepatotoxicity. In humans exposure to FB1 is linked with higher incidence of primary liver cancer and oesophageal cancer, which are frequent in certain regions of the world (such as Transkei region in South Africa) where maize is staple food. The occurrence of neural tube defect in children in some countries of Central America (such as Mexico and Honduras) is connected with the consumption of FB1-contaminated maize-based food. However, possible involvement of FB1 in the development of human diseases is not clear. Nevertheless, the International Agency for Research on Cancer (IARC) has classified FB1 as a possible carcinogen to humans (group 2B).

FB1 is a causative agent of ELEM, a brain disorder in equines, indicating that brain is a target organ of FB1 toxicity. Several studies on experimental animals or on cell cultures of neural origin have established that FB1 has a neurodegenerative potential, although the mechanism of its neurotoxicity is still vague. The aim of this article is to give an overview of available literature on FB1 neurotoxicity and involved mechanisms, and to offer a new perspective for future studies.

Fumonizin B1 (FB1) jest mikotoksin koji proizvode plijesni roda Fusarium spp. koje nalazimo kao onečišćivače žitarica, ponajprije kukuruza diljem svijeta. Od svih do sada izoliranih fumonizina FB1 se najčešće može naći na kukuruzu, a i najtoksičniji je fumonizin. FB1 ima različite toksične učinke ovisno o životinjskoj vrsti. Tako u konja izaziva leukoencefalomalaciju kopitara (ELEM), u svinja plućni edem, a za eksperimentalne je glodavce nefrotoksičan i hepatotoksičan. U ljudi je izloženost FB1 povezana s razvojem primarnog karcinoma jetre i karcinoma jednjaka koji se učestalo pojavljuju u regijama svijeta (kao Transkeiska regija u Južnoj Africi) u kojima ljudi rabe kukuruz u dnevnoj prehrani. I pojavljivanje defekta neuralne cijevi u nekim je zemljama Srednje Amerike (kao Meksiko i Honduras) povezano s učestalom konzumacijom kukuruzne hrane kontaminirane s FB1. Ipak se sa sigurnošću ne može povezati razvoj navedenih bolesti u ljudi s izloženosti FB1. Međunarodna agencija za istraživanje raka (IARC) klasificirala je FB1 kao mogući karcinogen za ljude (grupa 2B). Kako je FB1 uzročnik ELEM-a, poremećaja središnjega živčanog sustava (SŽS) u konja, to upućuje na mogućnost da FB1 uzrokuje promjene u mozgu. Nekoliko studija na pokusnim životinjama i na staničnim kulturama stanica podrijetlom iz SŽS-a potvrdilo je da je FB1 neurotoksičan iako mehanizam neurotoksičnosti FB1, pa tako i mehanizam njegove toksičnosti, još nije razjašnjen. Stoga je cilj ovoga rada dati pregled dostupne literature o neurotoksičnosti i mehanizmu neurotoksičnosti FB1 kako bi se omogućilo bolje planiranje budućih istraživanja.

KEYWORDS : equine leukoencephalomalacia; neural tube defect; neurotransmitters; sphingolipids,sphingoid bases; oxidative stress; mitochondria

KLJUČNE RIJEČI : defekt neuralne cijevi; leukoencefalomalacija kopitara; mitohondrij; neurotransmiteri,oksidativni stres; sfingoidne baze; sfingolipidi

  • 1. International Programme on Chemical Safety (IPCS). Safety Evaluation of Certain Mycotoxins in Food. WHO Food Additives Series: 47. Geneva: WHO; 2001.

  • 2. Voss KA, Smith GW, Haschek WM. Fumonisins: Toxicokinetics, mechanism of action and toxicity. Anim Feed Sci Technol 2007;137:299-325.

  • 3. Gelderblom WCA, Jaskiewicz K, Marasas WFO, Thiel PG, Horak RM, Vleggaar R, Kriek NP. Fumonisins-novel mycotoxins with cancer promoting activity produced by Fusarium moniliforme. Appl Environ Microbiol 1988;54:1806-11.

  • 4. Sorriano JM, Dragacci S. Occurence of fumonisins in foods. Food Res Int 2004;37:985-1000. [Crossref]

  • 5. Gelderblom WCA, Kriek NPJ, Marasas WFO, Thiel PG. Toxicity and carcinogenicity of the Fusarium moniliforme metabolite fumonisin B1 in rats. Carcinogenesis 1991;12:1247-51. [Crossref]

  • 6. National Toxicology Program (NTP). Technical Report on the Toxicology and Carcinogenesis Studies of Fumonisin B1 (CAS No. 116355-83-0) in F344/N Rats and B6C3F1 Mice (Feed Studies). National Toxicology Program 2001 [displayed 27 September 2012]. Available at http://ntp.niehs.nih.gov/ntp/htdocs/LT_rpts/tr496.pdf

  • 7. Bhat RV, Shetty PH, Amruth RP, Sudershan RV. A foodborne disease outbreake due to the consumption of moldy sorghum and maize containing fumonisin mycotoxins. J Toxicol Clin Toxicol 1997;35:249-55. [Crossref]

  • 8. Abnet CC, Borkowf CB, Qiao Y-L, Albert PS, Wang E, Merrill AH Jr., Mark SD, Dong Z-W, Taylor PR, Dawsey SM. Sphingolipids as biomarker of fumonisin exposure and risk of esophageal squamous cell carcinoma in China. Cancer Causes Control 2001;12:821-8. [PubMed] [Crossref]

  • 9. Sadler TW, Merrill AH, Stevens VL, Sullards MC, Wang E, Wang P. Prevention of Fumonisin B1-induced neural tube defects by folic acid. Teratology 2002;66:169-76. [PubMed] [Crossref]

  • 10. Gelineau-van Waes JB, Starr L, Maddox JR, Aleman F, Voss KA, Wilberding J, Riley RT. Maternal fumonisin exposure and risk for neural tube defects: mechanisms in an in vivo mouse model. Birth Defects Res A Clin Mol Teratol 2005;73:487-97.

  • 11. Missmer SA, Suarez L, Felkner M, Wang E, Merrill Jr. AE, Rothman KJ, Hendricks KA. Exposure to fumonisins and the occurrence of neural tube defects along the Texas-Mexico border. Environ Health Perspect 2006;114:237-41.

  • 12. Detrait ER, George TM, Etchevers HC, Gilbert JR, Vekemans M, Speer MC. Human neural tube defects: developmental biology, epidemiology, and genetics. Neurotoxicol Teratol 2005;27:515-24. [PubMed] [Crossref]

  • 13. Mitchell LE. Epidemiology of neural tube defects. Am J Med Genet C Semin Med Genet 2005;135:88-94.

  • 14. International Agency for Research on Cancer (IARC). Some traditional herbal medicines, some mycotoxins, naphthalene and styrene. IARC monographs on the evaluation of carcinogenic risks to humans. Vol. 82. Lyon: IARC; 2002.

  • 15. Wilson TM, Ross PF, Rice LG, Osweiler GD, Nelson HA, Owens DL, Plattner RD, Reggiardo C, Noon TH, Pickrell JW. Fumonisin B1 levels associated with an epizootic of equine leukoencephalomalacia. J Vet Diagn Invest 1990;2:213-6. [PubMed] [Crossref]

  • 16. Ross PF, Rice LG, Reagor JC, Osweiler GD, Wilson TM, Nelson HA, Owens DL, Plattner RD, Harlin KA, Richard JL, Colvin BM, Banton MI. Fumonisin B1 concentrations in feeds from 45 confirmed equine leukoencephalomalacia cases. J Vet Diagn Invest 1991;3:238-41. [PubMed] [Crossref]

  • 17. Wilson BJ, Maronpot RR. Causative fungus agent of leukoencephalomalacia in equine animals. Vet Rec 1971;88:484-6. [Crossref]

  • 18. Marasas WFO, Kellerman TS, Gelderblom WCA, Coetzer JAW, Thiel PG, van der Lugt JJ. Leukoencephalomalacia in a horse induced by fumonisin B1 isolated from Fusariummoniliforme. Onderstepoort J Vet Res 1988;55:197-203.

  • 19. Kellerman TS, Marasas WFO, Thiel PG, Gelderblom WCA, Cawood M, Coetzer JAW. Leukoencephalomalacia in two horses induced by oral dosing of fumonisin B1. Onderspoort J Vet Res 1990;57:269-75.

  • 20. Ross PF, Ledet AE, Owens DL, Rice LG, Nelson HA, Osweiler GD, Wilson TM. Experimental equine leukoencephalomalacia, toxic hepatosis, and encephalopathy caused by corn naturally contaminated with fumonisins. J Vet Diagn Invest 1993;5:69-74. [Crossref] [PubMed]

  • 21. Osuchowski MF, Sharma RP. Fumonisin B1 induces necrotic cell death in BV-2 cells and murine cultured astrocytes and is antiproliferative in BV-2 cells while N2A cells and primary cortical neurons are resistant. Neurotoxicology 2005;26:981-92.

  • 22. Bucci TJ, Hansen DK, Laborde JB. Leukoencephalomalacia and hemorrhage in the brain of rabbits gavaged with fumonisin B1. Nat Toxins 1996;4:51-2. [PubMed] [Crossref]

  • 23. Pepeljnjak S, Petrik J, Šegvić Klarić M. Toxic effects of Ustilago maydis and fumonisin B1 in rats. Acta Pharm 2005;55:339-48. [PubMed]

  • 24. Kwon OS, Schmued LC, Slikker Jr. W. Fumonisin B1 in developing rats alters brain sphinganine levels and myelination. Neurotoxicology 1997;18:571-80. [PubMed]

  • 25. Kwon OS, Sandberg JS, Slikker Jr. W. Effects of fumonisin B1 treatment on blood-brain barrier transfer in developing rats. Neurotoxicol Teratol 1997;19:151-5. [PubMed] [Crossref]

  • 26. Kovačić S, Pepeljnjak S, Petrinec Z, Šegvić Klarić M. Fumonisin B1 neurotoxicity in young carp (Cypinus carpio L.). Arh Hig Rada Toksikol 2009;60:419-26.

  • 27. Harel R, Futerman AH. Inhibition of sphingolipid synthesis affects axonal outgrowth in cultured hippocampal neurons. J Biol Chem 1993;268:14476-81.

  • 28. Monnet-Tschudi F, Zurich MG, Sorg O, Matthieu JM, Honegger P, Schilter B. The naturally occurring food mycotoxin fumonisin B1 impairs myelin formation in aggregating brain cell culture. Neurotoxicology 1999;20:41-8.

  • 29. Kwon OS, Slikker Jr. W, Davies DL. Biochemical and morphological effects of fumonisin B1 on primary cultures of rat cerebrum. Neurotoxicol Teratol 2000;22:565-72. [Crossref] [PubMed]

  • 30. Galvano F, Campisi A, Russo A, Galvano G, Palumbo M, Renis M, Barcellona ML, Perez-Polo JR, Vanella A. DNA damage in astrocytes exposed to fumonisin B1. Neurochem Res 2002;27:345-51. [PubMed] [Crossref]

  • 31. Mobio TA, Anane R, Baudrimont I, Carratu M-R, Shier TW, Dano SD, Ueno Y, Creppy EE. Epigenetic properties of fumonisin B1: cell cycle arrest and DNA base modification in C6 glioma cells. Toxicol Appl Pharmacol 2000;164:91-6.

  • 32. Mobio TA, Tavan E, Baudrimont I, Anane R, Carratu M-R, Sanni A, Gbeassor MF, Shier TW, Narbonne J-F, Creppy EE. Comparative study of the toxic effects of fumonisin B1 in rat C6 glioma cells and p53-null mouse embryo fibroblasts. Toxicology 2003;183:65-75.

  • 33. Stockmann-Juvala H, Mikkola J, Naarala J, Loikkanen J, Elovaara E, Savolainen K. Fumonisin B1-induced toxicity and oxidative damage in U-118MG glioblastoma cells. Toxicology 2004;202:173-83.

  • 34. Stockmann-Juvala H, Mikkola J, Naarala J, Loikkanen J, Elovaara E, Savolainen K. Oxidative stress induced by fumonisin B1 in continuous human and rodent neural cell cultures. Free Rad Res 2004;38:933-42.

  • 35. Domijan A-M, Abramov AY Fumonisin B1 inhibits mitochondrial respiration and deregulates calcium homeostasis - implication to mechanism of cell toxicity. Int J Biochem Cell Biol 2011;43:897-904. [Crossref]

  • 36. Stockmann-Juvala H. Naarala J, Loikkanen J, Vahakangas K, Savolainen K. Fumonisin B1-induced apoptosis in neuroblastoma, glioblastoma and hypothalamic cell lines. Toxicology 2006;225:234-41.

  • 37. Burke WJ, Li SW, Chung HD, Ruggiero DA, Kristal BS, Johnson EM, Lampe P, Kumar VB, Franko M, Williams EA, Zahm DS. Neurotoxicity of MAO metabolites of catecholamine neurotransmitters: role in neurodegenerative diseases. Neurotoxicology 2004;25:101-15. [PubMed] [Crossref]

  • 38. Frederick AL, Stanwood GD. Drugs, biogenic amine targets and the developing brain. Dev Neurosci 2009;31:7-22. [PubMed] [Crossref]

  • 39. Porter JK, Voss KA, Bacon CW, Norred WP. Effects of Fusarium moniliforme and corn associated with equine leukoencephalomalacia on rat neurotransmitters and metabolites. Proc Soc Exp Biol Med 1990;194:265-9.

  • 40. Porter JK, Voss KA, Chamberlain WJ, Bacon CW, Norred WP. Neurotransmitters in rats fed fumonisin B1. Proc Soc Exp Biol Med 1993;202:360-4.

  • 41. Tsunoda M, Dugyala RR, Sharma RP. Fumonisin B1-induced increases in neurotransmitter metabolite levels in different brain regions of BALB/c mice. Comp Biochem Physiol Part C Pharmacol Toxicol Endocrinol 1998;120:457-65. [Crossref]

  • 42. Gbore FA. Brain and hypophyseal acetylcholinesterase activity of pubertal boars fed dietary fumonisin B1. J Anim Physiol Anim Nutrit 2010;94:e123-9. [Crossref]

  • 43. Banczerowski-Pelyhe I, Vilagi I, Detri L, Doczi J, Kovacs F, Kukorelli T.. In vivo and in vitro electrophysiological monitoring of rat neocortical activity after dietary fumonisin exposure. Mycopathologia 2001;153:149-56.

  • 44. Wang E, Norred WP, Bacon CW, Riley RT, Merrill AH Jr. Inhibition of sphingolipid biosynthesis by fumonisins. Implications for diseases associated with Fusariummoniliforme. J Biol Chem 1991;266:14486-90.

  • 45. Dragan YP, Bidlack WR, Cohen SM, Goldsworthy TL, Hard GC, Howard PC, Riley RT, Voss KA. Implications of apoptosis for toxicity, carcinogenicity and risk assessment: fumonisin B1 as an example. Toxicol Sci 2001;61:6-17. [PubMed] [Crossref]

  • 46. Domijan A-M, Peraica M. Carcinogenic mycotoxins. In: McQueen CA, editor. Comprehensive toxicology. Oxford: Academic Press; 2010. p. 125-37.

  • 47. Domijan A-M, Peraica M, Markov K, Fuchs R. Urine ochratoxin A and sphinganine/sphingosine ratio in residents of the endemic nephropathy area in Croatia. Arh Hig Rada Toksikol 2009;60:387-93.

  • 48. Schwarz A, Rapaport E, Hirschberg K, Futerman AH. A regulatory role of sphingolipids in neuronal growth. J Biol Chem 1995;270:10990-8.

  • 49. Gelderblom WCA, Smuts CM, Abel S, Snyman SD, Cawood ME, van der Westhuizen L, Swanevelder S. Effect of fumonisin B1 on protein and lipid synthesis in primary hepatocytes. Food Chem Toxicol 1996;34:361-9. [Crossref]

  • 50. Stevens VL, Tang J. Fumonisin B1-induced sphingolipid d e p l e t i o n i n h i b i t s v i t a m i n u p t a k e v i a t h e glycosylphosphatidylinositol-anchored folate receptor. J Biol Chem 1997;272:18020-5.

  • 51. Sadler TW, Merrill AH, Stevens VL, Cameron Sullards M, Wang E, Wang P. Prevention of Fumonisin B1-induced neural tube defects by folic acid. Teratology 2002;66:169-76. [Crossref]

  • 52. Desai K, Cameron Sullards M, Allegood J, Wang E, Schmelz EM, Hartl M, Humpf H-U, Liotta DC, Peng Q, Merrill AH, Jr. Fumonisins and fumonisin analogs as inhibitors of ceramide synthase and inducers of apoptosis. Biochim Biophys Acta 2002;1585:188-92.

  • 53. Mobio TA, Baudrimont I, Sanni A, Shier TW, Saboureau D, Dano SD, Ueno Y, Steyn PS, Creppy EE. Prevention by vitamin E of DNA fragmentation and apoptosis induced by fumonisin B1 in C6 glioma cells. Arch Toxicol 2000;74:112-9. [PubMed] [Crossref]

  • 54. Myburg RB, Needhi N, Chuturgoon AA. The ultrastructural effects and immunolocalisation of fumonisin B1 on cultured oesophageal cancer cells (SNO). S Afr J Sci 2009;105:217-22.

  • 55. Yin J-J, Smith MJ, Eppley RM, Page SW, Sphon JA. Effects of fumonisin B1 on lipid peroxidation in membranes. Biochim Biophys Acta 1998;1371:134-42.

  • 56. Abel S, Gelderblom WCA. Oxidative damage and fumonisin B1-induced toxicity in primary rat hepatocytes and rat liver in vivo. Toxicology 1998;131:121-31.

  • 57. Domijan A-M, Želježić D, Milić M, Peraica M. Fumonisin B1: oxidative status and DNA damage in rats. Toxicology 2007;232:163-69.

  • 58. Domijan A-M, Kovac S, Abramov AY. Impact of fumonisin B1 on glutamate toxicity and low magnesium-induced seizure activity in neuronal primary culture. Neuroscience 2012;202:10-6.

The subject of this article has partly been presented at the International Symposium “Power of Fungi and Mycotoxins in Health and Disease” held in Primošten, Croatia, from 19 to 22 October 2011


Published Online: 2013-01-16

Published in Print: 2012-12-01


Citation Information: Archives of Industrial Hygiene and Toxicology. Volume 63, Issue 4, Pages 531–544, ISSN (Print) 0004-1254, DOI: https://doi.org/10.2478/10004-1254-63-2012-2239, January 2013

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