A Review of Fumonisin Production by Fusarium moniliforme and Fumonisin Toxicosis in Animals1

431993 Applied Poultry sdmy Inc

A REVIEW OF FUMONISIN PRODUCTION BY FUSARIUM MONILIFORME AND FUMONISIN TOXICOSIS IN ANIMALS~

Primary Audience: Toxicologists, Veterinarians, Production Supervisors, Feed Oualitv Control Personnel

DESCRIPTION OF PROBLEM The fumonisii are a group of toxic metabolites produced by the molds Fusarium monilifome, I? pml~eratumand E nygamai [1,2].These molds are characterized as ubiquitous, therefore, the Likelihood of feedstuffs being infested with toxigenic strains of these species of Fusarium is high. Between 1971and 1974, several field outbreaks of leukoencephalomalacia occurred in horses in South Africa 1

Microbiological examination of the ingredients used to formulate the rations of affected animals showed that E monilifonne was the predominant mold in the feed [3]. The production of the fumonisins in agricultural commoditiesby Fusarium species depends on such factors as geographical region, season, and the conditions under which the particular grain is grown, harvested, and

This manuscript is a revision of the introductory chapter to the thesis of Michael H. Henry, submitted in partial fulfiieot of the requirements for a Master of Science degree in the Department of Poultry Scieoce at The Univeristy of Georgia. Tbe complete thesis is available in The University of Georgia Science Library. To whom correspondence should be addressed ,

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MICHAEL H.HENRY and R.D. WYA+ Deportment of Poultry Science, The Universityof Georgia Riverbend Resemh Laboratory, Room 112,110Rivenbend Road Athens, GA 30605 Phone: (706) 542-1390 FAX: (7M)542-1390

Review Article HENRY and WYAlT

solvent partition with chloroform, and successive column chromatography on Amberlite XAD-2silica gel, followed by preparative HPLC purification. When using this technique, the fumonisins can be obtained from culture material with approximately 42% recoveryof the total fumonisii and with a purity of 85-100% [19,ul].

TOXICITY OF FUMONISINS

Contamination of corn with h i levels of fumonisii has been reported in the U.S., South Africa, and China, resulting in economic losses to farmers and a health hazard to farm animals and humans [U,161.In areas of South Africa where high incidences of esophageal Cancer in humans have been reported, concentrations of fumonisii Bi found in corn, a dietary staple, were extremely high (21, 221. Equine and porcine species appear to be the most susceptible to fumonisii toxicosis [23], however, the fumonisins also demonstrate some toxicityto poultry and rats [24,25,26,27l. Fumonisim B1 induces liver carcinoma in rats and horses [a, 291,but lacks activity in the Salmonella mutagenicityassay and in both the in vitro and in vivo DNA repair assays using primary rat hepatocyte (30,311. Fumonisii Bi was shown to be toxic to chicken macrophage OF and renal 0eUs of rats in in vitro experiments, but the mechanism of toxicity is not known [32, 331. The structural similarity of the The chemical structures of the fumonisii have been determined as 2-amino-12,16 fumonisii to sphingosine, (a component of dimethyl-14,15-propane-1,2,3-tricarboxyl sphingo-lipids) has led researchers to investiiCoSane, with hydroxyl groups attached to the gate the effects of fumonisins on the long carbon backbone (141.Although several sphingolipidpathway. I n v i m studies have also fumonisins have been characterized, only shown that fumonisii €31 and B2 are potent inhibitors of sphingolipid biosynthesis in rat fumonisii B1, Ba and B3 have been detected in nature [l5,16]. The fumonisiins are water hepatocytes and renal cells [33,34]. Ponies, pigs, and rats fed either purified fumonisiiBi soluble compounds,but will also dissolve in a or E monilifom culture material with 'a mixture of chloroform and methanol. The fumonisins are nonfluorescent compounds known concentration of fumonisii Bi, exhibit and do not absorb UV or visible light. Analyt- signiGcant changes in the sphinpanindsphingosine ratio in serum (35,361. These findings ical detection of the fumonisii is possible by suggest that fumonisii act on 'neurological making derivatives that either fluoresceor abfunction and cell membrane integrity. 17,181. sorb W light [Ci, Corn infested with E moniIifome has Efforts to isolate and purify large quantibeen associafed with human esophageal canties of the fumonisii in for evaluation of accer risk in Transkei, South Africa (371, and in tivity and metabolism in, and toxicity to farm animals have beentime consuming and expen- China, where corn is a dietary staple [a]. Sydenham et d.[21], detected significantly sive. Current isolation techniques for the fumonisins involve extraction of fumonisii- higher concentrationsof fumonisiiBi and B2 in corn samples from high esophageal cancer contaminated material with either metharate areas than in correspondingsamples from nolwater (31) or acetonitrilewater (l:l),

CHEMICAL PROPERTIES FUMONISINS

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stored. Grains grown in subtropical and trop ical regions are prone to fumonisiicontamination due to the relatively long and warm growingseason. Corn and sorghum are, by far, the two agricultural commoditiesthat seem to have the highest risk of cootamination [2]. In a recent survey [4], %% of the corn samples collected from corn produced in Indiana was infested with E r n d i f m e . Other feed ingredients such as wheat, barley, peanuts, cotton, and rice are also susceptible to fumonisin contamination due to infestationby E monilifome [5,6,7,8,9,10]. Although these commodities are important as substrates, moisture level and temperature are the critical factors regulating the growth of E moniliforme and the production of fumonisii [ll].Information on the minimal, optimal, and maximum temperature for fumonisii production is incomplete; however, the temperature range for fumonisii production is 203°C [12]. Corn cootaminated with fumonisin, and outbreaks of equine leukoencephalomalacia and porcine pulmonaryedema havebeen associatedwithdrought conditions in the Midwestern and Southeastern United States [4,l3].

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poults fed a diet with 200 pprn of fumonisin Bi were 25% less efficient than the controls [XI. Broiler chicks fed diets containing 300 ppm of fumonisii Bi exhibited a decrease of approximately20% in body weight gain, an increase in relative liver weight, and a decrease in relative bursa weight. Histological studies of the liver revealed biliary hyperplasia and Kupper-cell hyperplasia (271. Similar decreases in body weight gain were observed in rats and mice receiving diets containing purified fumonisii [W, 451. The changes observed in the livers of chickens are similar to those of rats and horses dosed with purified fumoniSi B1, but brain and lung damages seen in horses and pigs were not observed in chickens. Diarrhea and other clinical changeswere observed in the small intestine, however, these signs were considered nonspecific. In vitro experiments investigating the effect of purified fumonisii B1 chicken macrophage indicate that fumonisii may affect the avian immune system, possibly resulting in increasedsusceptibility of chickens to infectious diseases 1321. The similarity in liver changes seen in rats and horses dosed with purified fumonisin Bi, and the changes in livers of chicken consuming culture material with fumonisis, indicates that fumonisii is responsible for the toxic effects seen in poultry. Until purified fumonisin is available in quantities large enough for field trials, the characterization of fumonisin toxicity in poultry will remain incomplete.

CONCLUSIONS Fusarium monififonne and other toxigenic strains of Fwarium are prevalent in a variety of feedstuffs and can grow over a rather wide

range of environmental temperatures and moisture levels. The production of fumonisins appears to be correlated with the growth of these molds. The most obvious toxicological manifestion of fumonisii on livestock seems to be leukoencephalomalacia in horses and cattle, and pulmonary edema in swine. A relationship between fumonisiiingestion and esophageal cancer in humans has been postulated. The toxicological effects of fumonisii on poultry is unclear, however, poultry appear to be somewhat refractiveto the fumonisins.This indication is based upon preliminary studies utilizing E moniliforme-contaminatedculture

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low rate areas. Although the concentrationsof fumonisii found in corn were extremely high, the association between esophageal cancer and fumonisin is only suggestive. In addition, E monifgomae is known to produce other mycotoxins (;.e7 zearalenone, moniliformin,etc.) which may be related to the development of esophageal cancer. The toxicity of fumoniSin B1 in horses, pigs, and rats is well documented. Horses and ponies fed or injected with fumonisii B1 exhibit elevated serum aspartate tramamitwe, alkaline phosphatase, and y-glutamyltransferase activities [29,391. Histopathological evaluation of horse liver tissue revealed swelling and hydropic degeneration of mostly the centrilobular and midzone hepatpcytes [B]. In rats, hunonisii Bi causes decreased body weeight and feed consumption,and increased levels of serum alanine aminotransferase, aspartate transaminase, and alkaline phosphatase. Fumonisin B1 was also hepatotoxic and carcinogenic in long-term feedingstudies with rats [24, 251. Pigs fed or injected with fumonisii Bi exhibited pulmonary edema, hydrothorax, and liver damage (40,4% 42,431. Information on the toxic effects of fumonisin Bi to poultry is incomplete. However, field analysesindicatedthat fumonisiiB1 at 20 ppm or more in diets is associated with elevated 10- and 3O-day mortality, as well as feed refusal in commercial broiler flocks. Investigation of the effects of fumonisii in poultry has been limited to the use of culture material contaminated with fumonisii where the contaminated material was incorporated into thediet. ExperimentswithEmonUifmecontaminated culture material can lead to confusiig results and erroneous conclusions due to the high probability of other toxic metabolites being present in the contaminated material. Nevertheless, such recent experiments indicate that feed contaminated with fumonisin-producing fungi can cause some adverse responses in poultry (26,27,44]. Fumonisii B1 fed to broiler chicks for 21 days at levels of 450 to 525 ppm caused decreased body weight gain an4 feed intake. Increased liver, kidney, and 'proventriculus weights were noted as levels of fumonisii Bi increased [44]. Experiments with turkey poults using culture material with fumoniSi B1 concentrations of 100 or 200 ppm gave results similar to those for broiler chicks. %key

FUMOMSIN TOXICOSIS

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a common effect of fumonisin ingestion in most animals, is indicative of possible neurological site of adion. Furthermore, this effect indicates an alteration of cell membrane integrity, which may influence animal health in a variety of ways.

1. Ross, P.E, P.E Nelson, J.L Richard, C.D. Oswelkr, LC. Rku, RD. Plattner and T.M. Wuron, 1990. Productioaoffumonisins -. and Fufiarium 3 t e s ssociaEF%Z&tine leukoence halomalacia and pulmona edema in swine. t ! ! . Microbiol. ~322S-32%?rolnc 2. Thkl, P.C., W.F.0 Marasas, EW. Sydeaham, C.S. Sbcphmrd, W.C.A. Geldcrblom, and JJ. Nknrcnhuls, 1991. Sumyd f u d m n h p r p d u c t h -specie. Appl. Envimn. Minobid.S731089-

1. Chem. SOC. Chem. Commun. pp.74S745. 15. Sy&nham, EW., W . U Cclderblom, P.C. Thkl, lad W.F.O. Mussrc, 199oa. Evidence of the natural ocf(Lmnce of fumonisin Bi. a m t o x i n ~roduccdbv Fusariummonilifonne. i n cor'n. J. A&. Fooh Cbem. 38:285-290. 16. Ross, P.F., LG. Rke, C.D. Omeikr, P.E Nekon,

L. leekmnscia

3. Pienmar, J.C., T.S. Kellcrman, 8 n d W.F.0.M1981. Field outbreaks of i? h?ms consuming.mab in-

in

South Africa. J. S.M m & % M y 4. H o w , C,1992 Indiana only state reportin horse deaths due to fumonisin-contaminatcdgrain. d s t u f f s , March 3,1992. 5. Ogaw? K uyI S T a M q 1990. Population of field' benomyi-rrastant nce 'bakanae" fun Soc. Ann. Phytopathol. Japan 56:247-%.in 6. Moubaher, AH., M A Elnrghy, and S L -1Hafez, 1972. Studies on the fungus flora of t k p i n s in Egypt. Mppathologia 473261-274. 7... Bain, D.C, 1973. Association of Purarium with infection of K) um r e d l i n g by Phytopathd. 63%-198. 8. W a m n , ILL rod T. Kommcd.hl, 1973. fkrtilizaassocition and wheat refuse effectson Fusprium a t e d with wheat roots in c e s o t a . Phytopathol. 63:103-108. 9. Laelere. R. 1973. Cotton Boll rots in Sene~ k 1 I . F ~ gisdlated gi from boll duringrot. Cotonet Fibres rop. 28:493-507. 10. HacA, W.R Rosser, and M.T. DeniSh, 1976. Zearalenonc-producin species of &a&m on barley. Ann. Appl. Btol. 84:7-f1. 11.Smlth, LE and R S Henderson, Eds. Mycotoxins and Animal Foods, 1991, CRC Press, Inc.Boca Raton, F L 12. Albds, J.F., W A C Celdcrblom, P.C. Thlcl, W.F.O. Mrr~ses,DJ. Van Scbnlkrirylr, Y. B e ~ n d , 1990. Effects of temoeraturc and mcubation oenod on prodGion of fumoiiiiin BI ~usarium m0;lilirOrme. Appl. Environ. Microbiol. S73%9-1733. 13.Wibon, T.M., P.F. Ross,LC. We,C.D. oswtiler, H A Nelson, D.L Owem, RD. PlaUner, C R&rdq T.H.Noon, and J.W. Pkhrll, 1990. Fumonisin Bi kvcls associated with a n epizootic of c uine leukoencephalornalacia.J. Vet. Diap. Invest. 2211216. 14. Bezeuidenhoul, S.C, WAC. Celderblom, C.P. Crost-Allman, RM. Honk, W.F.O. Marasus, C. Spi(cUer, and R Vlcggar, 1988.Structuralcludication

ofthe fumonisin mycotoxinsf r o m m m o n i l i f n r m e .

1.L Richard, d T.M. Wibon, 1992. A review and update of animal toxmscs d a t e d with fumonisii-contaminated feed and production of fumonisins by Fhmium isolates. Mympathologia 1173109-114. 17. Plattoer, RD., W.P. Norred, CW. Bacon, KAV- R P t k r s ~ l qD.D. S h . e k d l O r d , pod D. W~isleder, 1990. A method of detection of fumonisins in corn samples associated with field cases of equine kukoencephalomalaica. M p l o g i a a698-702. 18. Sbephard,CS, EW. Sydcnham, P.C. Thtel, and W . U Cekkrblom, 1990.Quantitative determinationof fumonisin Bi and Bzby high-pexfonnance liquid chromatography with fluorescence detection. J. Liq. Chromat-. 13:207-X%7. 19. Celderblom, W.C.A., W.F.O. Marasas, R Vlcggaar, P.C. Thiel, 8nd M.E Cawood, 1992. Fumonisins: Isolation, chemical characterizationand biological effects. Mycopathologia 11211-16. 20. Plattner, RD., D. Weislcder, D.D. Shackelford, R Pelcrson, and RG. PoweU, 1992. A new fumonisin .. from solid cultures of Eusahn nmulhmc Mycopathologia 11723-28. 21. Sydcnham, EW., P.C. Thkl,W.F.O. Marasas, C.S Shephard, DJ. Van SchaUnvyk, and KR Koch, 199Ob. Natural occumnce of some Fusarium mycotoxins in corn from low and high esopha ea1 cancer prevalence areas of Trankei, southern A h a . J. Agric. Food Chem. 38:1900-1903. 22. Thkl, P.C., W.F.0 Marasas, EW. Sydenham, C.S. Sbephard, and W.CA. Celderblom, 1992. The implications of naturally occurring levcls of fumonisins in corn f o r human and animal health. Mycopathologia1173-9. 23. Ross, P.F., LC. Rice, RD. Plather, G.D. Oswelkr, T.M. Wilson, D.L Owens, H A Nelson, and LL Richardsj 1991. Concentration of fumonisin Bi in feeds associated with animal health problems. Mycopathdogia 114129-135. 24. Voss, LA., RD. Plattoer, C.W. Bacon, and W.P. Norred, l990.Com rativestudiesofhepatotoxicity and fumonisin BI and g c o n t e n t of water and chlomform/methanol extracts of Fusarium monlllformc strain MRC 826 culture material. Mppathologia 11281-92. 25. Ccldcrblom, W.C.A., N.P.J. Kriek, W.F.O. Marasas, and P.C. Thlel, 1.T'. Toxicity and carcinogenicity of Fusarium monlllformc metabolite, fumonisin Bi, in rats. Carcinogenesis 121247-1251.

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material with known concentrations of fumonisin in the diets of chickens and turkeys, and a comparison of these effects to the concentrations of fumonisii produced in nature. The alteration in sphingosine biosynthesis and sphinganindsphingosine ratios in SCNUI,

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36.RUey, RT.,N.Y. An, J.L Sbowkcr, H.S. Yoo, W.P. Norred, WJ. Chambedah, E Wan& AH. MerrW Jr., G.Molclia, V A &.sky, and W.M. H-belr, 1992. Alteration of tissue and serum sphinpnine to sphingarine ratio: An early biomarker in gip of exposure to fumonisincontaining fceds Unpu Lhed. 37. MaW.F.O., F.C Weber, SI. v a n Rembur&uwl SJ. van Sclrbplkuyk, 1981. Mycoflora of corn p m d d in human csoph.gul cancer areas OfTranskei, southern Africa. Pbytopathd. 7l:7!?2-796. 38.Y q CS, 1980. Rtrrcareh on esophageal cancer in China: a review. Cancer Res. 4Ct2633-2644. 39. Wilson, T.M., P.F. Ross, D.L Owens, LC.Rice. SA C-4 SJ.JenLLm, d H A Nelson, 1992. Expcrimental reproduction &ELEM: Astudy to determine the minimum toxic dosc m ponies. Mycopathologia 117:115120. 40. Harrison, LR., B.M. Colvin, TJ. Crecne, LE Ncwnmn, and J.R Cok, 1990. Pulmonaty edema and hydrothorax in swine pmd+.by fumonisin Bi, a t0Jk metobdite d Pusarium Vet. Diagn. Invtrt. 2217-221. 41. CoMn, B.M. and LR Harrison, 1992. Fumonisininduced pulmona edema and hydrothorax in swine. Mycopnthdogi? 111;:79-82 42. Osrrlkr, C.D., P.F. Ross,T.M. Wilson, P.E Ncl~ son,ST.Wlc,T.L Carson,LC. Rkc,and H A Nelson, 1992. Characterization of epizootic pulmonay edema in swincssociatedwithfumonisinincornscnxnings.J.Vet. Diagn. lnvcst. 453-59. 43. Hascbek, W.M., C. Molelin, D.K. Ness, 1Gs H u l l q W.F. Hall, RF. Vesonder, RE P e k m n , and V A k k y , 1992. Characterization of fumonisin toxicity i n orall intravenously dosed swine. Mppathologia ll&-%. 44. WcibWry T.S., D.R Ltdoux, AJ. Bermudeq and C.E Roltingtmus,1992. E f f c c t s o f ~ m o n i l i f o r m e culture material containing known levels of fumonisin Bt on broiler chicks (Abstract). Poultry Sci. 71: Suppl.:183. 45. Voss, K.A., W.P. Nomd, and CW. Becon, 1992. Subehronic toxicology investigation of Eusahm contaminated corn, cultural material, and ammoniated culture material. Mycopathologia 117:97104.

Downloaded from http://japr.oxfordjournals.org/ at University of Iowa Libraries/Serials Acquisitions on June 8, 2016

26. Ledoox, D.R., T.S. Wcibking, and C.ERotlIngham, 1992. Effects of Fusarium monilllonneculture material containing lrnowa levels of fumonisin BI on turkcypoults. PoultrySci. 71:Supl. M62. 27. Brorng T.P., G.E R o l U ~ g b - and M.E WIlliams, 1992Fumonisin * inbroikrsPerfor. -=A manee and patwogy. 28. Celderblom, W A C . , K. Jcrklcwicr, W.F.O. Marases, P.G. Tblcl, R Vleggaar, and N.PJ.Krkk, 198%. Novel-Mycotdn wifh cancer-promotingactivity roduccd =monlltForme. AflEnviron. M i d . 54:1&1*11. 29. Marases, W.F.O., T.S. Kcllcrman, W.CA Gclderblom, JAW. Coelatr, P.G. Tbkl, a d JJ. Vnn Der Logl, 1988. Leukoma alomalacia in h o w induced by fumonisin Bt isoIa&mm Fucan’um OaaerstepoortJ. Vet. RCS.55:197-#n. 30.Gclderbbm, WAC,and SD.Loow, 1991. On the mutagenicity $potentially carcinogenicmycotoain of& sarivmmonllrFonae.Mycotoxin Res. 7:46-5% , Tbkl, 31. Cclderblom,W A C , W.F.O. M ~ c p c gP.G. E Sempk, and E Fuber, 1989. Possible non-genotoatic active.prciiaopenic components produced by montllforme. Proc. Am. Acsoc. Cancer Rcs w.144. 32. Q-M, M A and W.M. H e r , Jr. 1992. Meet dfumontsln Bion chicken macrophage f u n c t i o n s ~ Poultry Sci. 7 l : l W l l L 33.Wnnb, E,W.P. Norred, CW.Bacon, RT. Riley, and AH. M e d Jr., 1991. lnhibitioa of sphingolipid biosMthesis bv fumoakins imdicatiuas for diseases ass o c h t e d wrth Pusarium Imonilifonne. J. Biol. Chem. 26694486-14490. 34. Nonwl, W.P., E W q Y. Hwansoo, RT. RUey, and AH. Mcrrill, Jr., 1992. In &Q toxicology of fumonirins a n d the mechanistic implications. Mycopathologia 117:73-78. 35. Merrill, AH., E Wang, D.G. Cilchhrist, and RT. Riky, 1992. Fumoaisins and other inhibitom of dc ~ l ~ lsphingolipid yp biosynthesis. A&. Lipid Rta Submitted.