Toxins Project

ByJustin Sona

Cammie AtwaterMargaret Garcia

Zach Cecelic

Fusarium Toxins

Kingdom: FungiPhylum: Ascomycota

Genus: FusariumSpecies: Many

General: Why you might want to know about Fusarium mycotoxins

• Mycotoxins: secondary metabolites produced by fungus• In grains that are consumed by people• In feed grains of animals that are eaten by people• fusarium mycotoxins can be:

Beneficial for plants Used as weapons and biological control Possible carcinogens Immuno-depressors Hepatotoxic Nephrotoxic A cause of Pre-puberty [i.e. earlier onset of puberty]

(controversial) Damaging economically due to crop loss

Varies among season and region

Introduction

• These toxins are produced by fungi that grow mainly on corn, wheat, oats, and other cereals.

• The levels of toxin produced are influenced by environmental factors High levels produced when

hot dry weather which is fallowed by humidity Plants are damaged by insects/birds

• Most are heat resistant Even if grains are cooked, mycotoxins still present

(Fink-Gremmels, 1989).

General: Environmental role

• While these mycotoxins are harmful to mammals, they actually improve root growth of crops like corn.

• They enable crop plants to survive through dry conditions and other stresses (Lee 2000).

Ethnobotany

• Indigenous people in the Andes and Amazon have suffered from mycotoxins which have compromised plants, such as the coca and poppy which can be used for medicinal purposes. (The Sunshine Project 2001)

• Fusarium oxysporum has been known to kill coca, and has been used by US government in an attempt to eradicate coca. (Zielonka et al. 2009 )

Fusarium oxysporum www.answers.com/topic/fusarium-oxysporum

Mycotoxins Produced

• More then 10 forms of fumonisin have been isolated

• We focused on: Trichothecenes

Desoxynivalenol Nivalenol

Zearalenon Fumonisin B1 and B2

Trichothecenes

• Effects of poisoning Vomiting, Diarrhea, food rejection, GI

inflammation, tissue necroses and impairment of: nerves, heart, lymph system, testes, and thymus

immunodepression• LD50: 10.5mg/kg in mice• Growth

Mainly on dry grains in warm conditions

Trichothecenes

• Most dangerous of the mycotoxins• Mechanism

Inhibits protein synthesis by chemical inactivation of ribosomes

Acts like an estrogen and inhibits division of rapidly growing cells (i.e. intestine lining and bone marrow) (Obremski et al. 2008).

Inhibits/weakens effect of blood clotting

Trichothecenes: Weapon Potential

• Intensely irritating effects on the skin immediately active upon touching skin (Bunner et

al., 1985)

• Attempt to use as topical poison and mucosal poison

• Used as a component in the weapon known as “yellow rain” (Croddy et al. 2005).

Trichothecenes: Medical Uses

• Investigated for its treatment of cancerous tumors

• Found to be too toxic for routine use (Croddy et al. 2005)

Desoxynivalenol

• A type of Trichothecene

• One of the most common mycotoxins found on animal feed (Zielonka et al. 2009).

Desoxynivalenol

• Mechanism Same as other Trichothecenes

• Effects of poisoning In plants

Growth depression, Immune system suppression

In humans Vomiting, rejection of nutrition, GI

inflammation

Nivalenol

• Oral LD50 (for mice): 38.9 mg/kg Death seen three days after exposure due

to: Congestion hemorrhage in the intestine

• Is a B-Trichothecenes Trichothecenes contain a tri-cyclic ring

system with various functional groups The B group has a carbonyl group on the

eighth carbon that distinguishes it from A, C and D (Eke et al. 2004)

Nivalenol: Medical Studies

• High levels of nivalenol found in food has been correlated with areas of high risk for esophageal cancer in China.

• Has been known to induce both benign and malignant tumors in mice.

• Studies in mice continue, to see if nivalenol must be ingested (vs skin contact) to have effects. (Hsia et al. 2004)

Zearalenone

• LD50 is >4000 up to >20,000 mg/kg Carcinogenic effect is assumed

• Binds to estrogen receptors Leads to disturbances in fertility in mice, rats,

guinea-pigs, hamsters, and rabbit• High levels in farm animals causes serve

morphological and function disorders of reproductive organs (Mirocha, C.J., and C.M. Christensen)

• May lead to pre-puberty in humans

(Mitterbauer et. al 2003).

Zearalenone: Affect on Ethno-botanical Medicine

• Tribulus terrestris is an herb grown in India and Sri Lanka for medicinal purposes.

• The storage conditions of this plant are often not controlled, allowing toxigenic fungi to grow.

• Zearalenone is often produced by the growing fungi

• Mycotoxins and their effects on stored medicinal plants is an area yet to be studied (Abeywickrama et al. 1992).

Fumonisin B1 & B2

• FB1 Most prevalent Fusarium toxin produced (Kim et al. 2008)

• Mechanism shared by FB1 and FB2 Inhibits sphingosine biosynthesis

Sphingolipids are lipids found in neural tissue Hepatoxic (Shepard et al., 1995)

Nephrotoxic Suspected to be carcinogenic in humans

(The Sunshine Project 2001).

Fumonisin B1 & B2

• FB2 is derived by the polyketide pathway

• FB2 is mainly produced by F. verticilloides and F. proliferatum (Apsimon,

2001) • Found mostly in maize-based human

food and animal feeds (Visconti, 1996).

• Most common fungus associated with corn intended for human consumption (Marasas, 2006)

Fumonisin B1 and B2

• Recently shown to be produced by Aspergillus niger in Thai coffee beans (Noonim et al. 2009)

• Natural occurrence in corn found all over the world, from Argentina to Egypt to Nepal (Marasas, 2006)

Fumonisin B1 and B2

Fumonisin produced by Fusarium

Maize in West Africa containing aflatoxin, dexoxynivalenol and fumonisin

Other Examples of toxic effects

Grain produced in heads damaged byFusarium head blight is often shriveled, white, and chalky in appearance.

Photos from www.cas.psu.edu

Wheat heads with symptoms of Fusariumhead blight. Diseased spikelets become (a)bleached or tan in appearance

Vulvar prolapse caused by mycotoxin Zearalenone contamination

www.engormix.com/images/e_articles/1127_02.jpg

Summary

• We presented a background on mycotoxins, specifically those of the genus Fusarium.

• Then, we moved on to the specific toxins, their mechanisms, their toxicities and their ecological and ethnobotanical roles.

• It is clear that this genus is a prolific producer of toxins and that it has a tremendous impact on humans and non-humans who eat grains that contain these fungi.

Conclusion

• Fungus is among us, and with lots of secondary metabolites that are harmful.

• As Americans we consume (nationmaster.com)

~33,203 metric tons of wheat ~221,726  metric tons of coarse grains

• What amount of mycotoxins are we accumulating by eating the grains, and the meat raised on these grains?

Possible future research

• How do agricultural practices influence the mycotoxins present and infection in crops (ie. Use of transgenic seeds, herbicides,fertilizers)?

• How do you reduced toxicity of mycotoxins in contaminated food, since there may be more than one toxin present? These toxins all have different characteristics.

• How will climate change affect plants and their relationship with these and other fungi that produce mycotoxins?

Works Cited

Abeywickrama, K., Bean G. A. (1992) Cytotoxicity of Fusarium species mycotoxins and culture filtrates of Fusarium species isolated from the medicinal plant Tribulus terrestris to mammalian cells. Mycopathologia. 120: 189-193.

Apsimon, J.W. 2001. Structure, synthesis and biosynthesis of Fumonisin B1 and related compounds. Environmental Health Perspectives 109: 245-249.

Croddy, E., Wirtz J.J., Larsen J.A. Weapons of mass destruction: an encyclopedia of worldwide policy, technology, and history. ABC-CLIO, 2005.

Eke, Z., Kende A., and Torkos, K. 2004. Simultaneous detection of trichothecenes A and B by gas chromatography with flame ionization or mass selective detection. Microchemical Journal 78: 211-216.

Fink-Gremmels, J. (1989). The significace of mycotoxin assimilation for meat animals. Dtsch. Tierarztl. Worchensschr 96: 360-363.

Hsia, C. C., Wu, Z. Y., Li, Y. S., Zhang, F., Sun, Z. T. (2004) Nivalenol, a main Fusarium toxin in dietary foods from high-risk areas of cancer of esophagus and gastric cardia in China, induced benign and malignant tumors in mice. Oncology Reports.  12: 449-456. 

Kim,B., Ejaz, S.,Chekarova,I., Sukura, A., Ashraf,M., Lim, C.W. (2008) Cytotoxicity of fumonisin B-1 in spheroid and monolayer cultures of rat hepatocytes. Drug and Chemical Toxicology: an International Journal for Rapid Communication 31: 339-352.

Lee, J. Corn Seed Pretreatment Reduces Fusarium. Agricultural Research. 2000.

Works Cited Cont.

Marasas, W. 2006. Fumonisins: Their implications for human and animal health. Natural Toxins 3: 193-198.

Mirocha, C.J., and C.M. Christensen. (1974). Estrogeneic mycotoxins synthesized by Fusarium, p 129-148. In I.F.H. Purchased (ed.), Mycotoxins. Elsevier, Amsterdam, The Netherlands.

Mitterbauer, R., Weindorfer, H., Safaie, N., Krska, R., Lemmens, M., Ruckenbauer,P., Kuchler, K., and Adam,G. (2003) A sensetive and inexpensive yeast bioassay for the mycotoxin zearalenone and other componds with estrogenic activity. Applied and Environmental Microbiology 69: 805-811.

Noonim, P., Mahakarnchanaku, W., Nielsen, K.F., Frisvad, J.F., and Samson, R.A. 2009. Fumonisin B2 by Aspergillus niger in Thai coffee beans. Food Additives and Contaminants 26: 94-100.

Obremski, K.; Zielonka, L.; Gajecka, M. (2008) Histological estimation of the small intestine wall after administration of feed containing deoxynivalenol, T-2 toxin and zearalenone in the pig. Polish Journal of Veterinary Sciences 11:339-345.

Risks of using Biological Agents in Drug Eradication. The Sunshine Project: A Briefing Paper with Emphasis on Human Health. 2001.

Shepard, G.S., Thiel, P.G., Sydenham, E.W., Snijman, P.J. 1995, “Toxicokinetics of the mycotoxin fumonisin B2 in rats” Food Chemistry and Toxicology., 33: 591-595,

Visconti A. Solfrizzo M:, Doko M.B., Boenke A., and Pascale M. 1996. Stability of fumonisins at different storage periods and temperatures in gamma irradiated maize. Food Additives and Contaminants 13:929-938.

Zielonka, L., Wisniewska, M., Gajecka, M. 2009. Influence of low doses of deoxynivanol on histopathology of selected organs of pigs. Polish Journal of Veterinary Science 12:89-95.

“Agriculture Statistics.” Nation Souce. 28 April 2008.  Web. 28 Apr. 2009.<http://www.nationmaster.com/graph/agr_gra_coa_gra_con_percap-coarse-grain-consumption-per-capita>