The role of roughage provision on the absorption and disposition of the mycotoxin deoxynivalenol and its acetylated derivatives in calves: from field observations to toxicokinetics.
Valgaeren et al 2018 The role of roughage provision on the absorption and disposition of the mycotoxin deoxynivalenol and its acetylated derivatives in calves from field observations to toxicokinetics.pdf
3- and 15-Acetyldeoxynivalenol; Biodegradation; Calf; Deoxynivalenol; Mycotoxin; Toxicokinetics
Abstract :
[en] A clinical case in Belgium demonstrated that feeding a feed concentrate containing considerable levels of deoxynivalenol (DON, 1.13 mg/kg feed) induced severe liver failure in 2- to 3-month-old beef calves. Symptoms disappeared by replacing the highly contaminated corn and by stimulating ruminal development via roughage administration. A multi-mycotoxin contamination was demonstrated in feed samples collected at 15 different veal farms in Belgium. DON was most prevalent, contaminating 80% of the roughage samples (mixed straw and maize silage; average concentration in positives: 637 +/- 621 microg/kg, max. 1818 microg/kg), and all feed concentrate samples (411 +/- 156 microg/kg, max. 693 microg/kg). In order to evaluate the impact of roughage provision and its associated ruminal development on the gastro-intestinal absorption and biodegradation of DON and its acetylated derivatives (3- and 15-ADON) in calves, a toxicokinetic study was performed with two ruminating and two non-ruminating male calves. Animals received in succession a bolus of DON (120 microg/kg bodyweight (BW)), 15-ADON (50 microg/kg BW), and 3-ADON (25 microg/kg) by intravenous (IV) injection or per os (PO) in a cross-over design. The absolute oral bioavailability of DON was much higher in non-ruminating calves (50.7 +/- 33.0%) compared to ruminating calves (4.1 +/- 4.5%). Immediately following exposure, 3- and 15-ADON were hydrolysed to DON in ruminating calves. DON and its acetylated metabolites were mainly metabolized to DON-3-glucuronide, however, also small amounts of DON-15-glucuronide were detected in urine. DON degradation to deepoxy-DON (DOM-1) was only observed to a relevant extent in ruminating calves. Consequently, toxicity of DON in calves is closely related to roughage provision and the associated stage of ruminal development.
Disciplines :
Veterinary medicine & animal health
Author, co-author :
Valgaeren, Bonnie ✱
Theron, Leonard ✱
Croubels, Siska
Devreese, Mathias
De Baere, Siegrid
Van Pamel, Els
Daeseleire, Els
De Boevre, Marthe
De Saeger, Sarah
Vidal, Arnau
Di Mavungu, Jose Diana
Fruhmann, Philipp
Adam, Gerhard
Callebaut, Alfons
Bayrou, Calixte ; Université de Liège - ULiège > Département de morphologie et pathologie (DMP) > Pathologie spéciale et autopsies
Frisee, Vincent ; Université de Liège - ULiège > Département clinique des animaux de production (DCP) > Département clinique des animaux de production (DCP)
Rao, Anne-Sophie ; Université de Liège - ULiège > Département de sciences des denrées alimentaires (DDA) > Microbiologie des denrées alimentaires
Knapp, Emilie
Sartelet, Arnaud ; Université de Liège - ULiège > Département clinique des animaux de production (DCP) > Département clinique des animaux de production (DCP)
✱ These authors have contributed equally to this work.
Language :
English
Title :
The role of roughage provision on the absorption and disposition of the mycotoxin deoxynivalenol and its acetylated derivatives in calves: from field observations to toxicokinetics.
Antonissen G, Martel A, Pasmans F, Ducatelle R, Verbrugghe E, Vandenbroucke V, Li SJ, Haesebrouck F, Van Immerseel F, Croubels S (2014) The impact of Fusarium mycotoxins on human and animal host susceptibility to infectious diseases. Toxins 6:430–452
Antonissen G, Van Immerseel F, Pasmans F, Ducatelle R, Janssens GPJ, De Baere S, Mountzouris KC, Su S, Wong EA, De Meulenaer B, Verlinden M, Devreese M, Haesebrouck F, Novak B, Dohnal B, Martel A, Croubels S (2015) The mycotoxins deoxynivalenol and fumonisins alter the extrinsic component of intestinal barrier in broiler chickens. J Agric Food Chem 63:10846–10855
Bennett JW, Klich M (2003) Mycotoxins. Clin Microbiol Rev 16:497–516
Berends H, Van den Borne J, Mollenhorst H, Van Reenen C, Bokkers E, Gerrits W (2014) Utilization of roughages and concentrates relative to that of milk replacer increases strongly with age in veal calves. J Dairy Sci 97:6475–6484
Bottalico A (1998) Fusarium diseases of cereals: species complex and related mycotoxin profiles, in Europe. J Plant Pathol 80:85–103
Bouhet S, Oswald IP (2005) The effects of mycotoxins, fungal food contaminants, on the intestinal epithelial cell-derived innate immune response. Vet Immunol Immunop 108:199–209
Bracarense APFL, Lucioli J, Grenier B, Pacheco GD, Moll W-D, Schatzmayr G, Oswald IP (2012) Chronic ingestion of deoxynivalenol and fumonisin, alone or in interaction, induces morphological and immunological changes in the intestine of piglets. Brit J Nutr 107:1776–1786
Broekaert N, Devreese M, De Baere S, De Backer P, Croubels S (2015a) Modified Fusarium mycotoxins unmasked: From occurrence in cereals to animal and human excretion. Food Chem Toxicol 80:17–31
Broekaert N, Devreese M, De Mil T, Fraeyman S, Antonissen G, De Baere S, De Backer P, Vermeulen A, Croubels S (2015b) Oral bioavailability, hydrolysis, and comparative toxicokinetics of 3-acetyldeoxynivalenol and 15-acetyldeoxynivalenol in broiler chickens and pigs. J Agric Food Chem 63:8734–8742
Broekaert N, Devreese M, van Bergen T, Schauvliege S, De Boevre M, De Saeger S, Vanhaecke L, Berthiller F, Michlmayr H, Malachová A, Adam G, Vermeulen A, Croubels S (2017) In vivo contribution of deoxynivalenol-3-β-d-glucoside to deoxynivalenol exposure in broiler chickens and pigs: oral bioavailability, hydrolysis and toxicokinetics. Arch Toxicol 91:699–712
Casteel S, Rottinghaus G, Johnson G, Wicklow D (1995) Liver disease in cattle induced by consumption of moldy hay. Vet Hum Toxicol 37:248–250
Craig AM, Pearson EG, Meyer C, Schmitz JA (1991) Serum liver-enzyme and histopathologic changes in calves with chronic and chronic-delayed Senecio jacobaea toxicosis. Am J Vet Res 52:1969–1978
Dänicke S, Matthäus K, Lebzien P, Valenta H, Stemme K, Ueberschär K-H, Razzazi-Fazeli E, Böhm J, Flachowsky G (2005) Effects of Fusarium toxin-contaminated wheat grain on nutrient turnover, microbial protein synthesis and metabolism of deoxynivalenol and zearalenone in the rumen of dairy cows. J Anim Physiol Anim Nutr 89:303–315
De Boevre M, Di Mavungu JD, Landschoot S, Audenaert K, Eeckhout M, Maene P, Haesaert G, De Saeger S (2012) Natural occurrence of mycotoxins and their masked forms in food and feed products. World Mycotoxin J 5:207–219
Devreese M, Antonissen G, Broekaert N, De Mil T, De Baere S, Vanhaecke L, De Backer P, Croubels S (2015) Toxicokinetic study and oral bioavailability of DON in turkey poults, and comparative biotransformation between broilers and turkeys. World Mycotoxin J 8:533–539
Driehuis F, Spanjer MC, Scholten JM, Te Giffel MC (2008) Occurrence of mycotoxins in maize, grass and wheat silage for dairy cattle in the Netherlands. Food Addit Contam B 1:41–50
Eriksen GS, Pettersson H (2004) Toxicological evaluation of trichothecenes in animal feed. Anim Feed Sci Technol 114:205–239
Eriksen GS, Pettersson H, Lindberg JE (2003) Absorption, metabolism and excretion of 3-acetyl DON in pigs. Arch Tierernahr 57:335–345
European Commission (1997) 97/2/EC of 20 January 1997 amending Directive 91/629/EEC laying down minimum standards for the protection of calves. Off J Eur Commun L 025:24–25
European Commission (2002) 2002/657/EC implementing council directive 96/23/EC concerning the performances of analytical methods and the interpretation of results. Off J Eur Commun L 221:8–36
European Commission (2006) 2006/576/EC commission recommendation of 17 August 2006 on the presence of deoxynivalenol, zearalenone, ochratoxin A, T-2 and HT-2 and fumonisins in products intended for animal feeding. Off J Eur Union L229:7–9
Fink-Gremmels J (2008) Mycotoxins in cattle feeds and carry-over to dairy milk: a review. Food Addit Contam 25:172–180
Fruhmann P, Warth B, Hametner C, Berthiller F, Horkel E, Adam G, Sulyok M, Krska R, Fröhlich J (2012) Synthesis of deoxynivalenol-3-beta-d-O-glucuronide for its use as biomarker for dietary deoxynivalenol exposure. World Mycotoxin J 5:127–132
Fruhmann P, Skrinjar P, Weber J, Mikula H, Warth B, Sulyok M, Krska R, Adam G, Rosenberg E, Hametner C, Fröhlich J (2014) Sulfation of deoxynivalenol, its acetylated derivatives, and T2-toxin. Tetrahedron 70:5260–5266
Fuchs E, Binder E, Heidler D, Krska R (2002) Structural characterization of metabolites after the microbial degradation of type A trichothecenes by the bacterial strain BBSH 797. Food Addit Contam 19:379–386
Gallo A, Giuberti G, Frisvad JC, Bertuzzi T, Nielsen KF (2015) Review on mycotoxin issues in ruminants: occurrence in forages, effects of mycotoxin ingestion on health status and animal performance and practical strategies to counteract their negative effects. Toxins 7:3057–3111
Gasthuys E, Vandecasteele T, De Bruyne P, Vande Walle J, De Backer P, Cornillie P, Devreese M, Croubels S (2016) The potential use of piglets as human pediatric surrogate for preclinical pharmacokinetic and pharmacodynamic drug testing. Curr Pharm Des 22:4069–4085
Gerez JR, Pinton P, Callu P, Grosjean F, Oswald IP, Bracarense APFL (2015) Deoxynivalenol alone or in combination with nivalenol and zearalenone induce systemic histological changes in pigs. Exp Toxicol Pathol 67:89–98
Goyarts T, Dänicke S (2006) Bioavailability of the Fusarium toxin deoxynivalenol (DON) from naturally contaminated wheat for the pig. Toxicol Lett 163:171–182
Heitzman RJ (1994) Veterinary Drug Residues, Report Eur. 14126-EN. Commission of the EC, Brussels-Luxembourg
Ingalls J (1996) Influence of deoxynivalenol on feed consumption by dairy cows. Anim Feed Sci Technol 60:297–300
Ji F, Wu J, Zhao H, Xu J, Shi J (2015) Relationship of deoxynivalenol content in grain, chaff, and straw with Fusarium head blight severity in wheat varieties with various levels of resistance. Toxins 7:728–742
King RR, Mcqueen RE, Levesque D, Greenhalgh R (1984) Transformation of deoxynivalenol (vomitoxin) by rumen microorganisms. J Agric Food Chem 32:1181–1183
Knutsen HK, Alexander J, Barregård L, Bignami M, Brüschweiler B, Ceccatelli S, Cottrill B, Dinovi M, Grasl-Kraupp B, Hogstrand C, Hoogenboom L, Nebbia CS, Oswald IP, Petersen A, Rose M, Roudot A-C, Schwerdtle T, Vleminckx C, Vollmer G, Wallace H, De Saeger S, Eriksen GS, Farmer P, Fremy J-M, Gong YY, Meyer K, Naegeli H, Parent-Massin D, Rietjens I, van Egmond H, Altieri A, Eskola M, Gergelova P, Bordajandi LR, Benkova B, Dörr B, Gkrillas A, Gustavsson N, van Manen M, Edler L (2017) Risks to human and animal health related to the presence of deoxynivalenol and its acetylated and modified forms in food and feed. EFSA J. 10.2903/j.efsa.2017.4718
Königs M, Schwerdt G, Gekle M, Humpf HU (2008) Effects of the mycotoxin deoxynivalenol on human primary hepatocytes. Mol Nutr Food Res 52:830–839
Kovalsky P, Kos G, Nährer K, Schwab C, Jenkins T, Schatzmayr G, Sulyok M, Krska R (2016) Co-occurrence of regulated, masked and emerging mycotoxins and secondary metabolites in finished feed and maize—an extensive survey. Toxins 8:363
Leruste H, Brscic M, Cozzi G, Kemp B, Wolthuis-Fillerup M, Lensink BJ, Bokkers EAM, van Reenen CG (2014) Prevalence and potential influencing factors of non-nutritive oral behaviors of veal calves on commercial farms. J Dairy Sci 97:7021–7030
Maresca M (2013) From the gut to the brain: journey and pathophysiological effects of the food-associated trichothecene mycotoxin deoxynivalenol. Toxins 5(4):784–820
Mattiello S, Canali E, Ferrante V, Caniatti M, Gottardo F, Cozzi G, Andrighetto I, Verga M (2002) The provision of solid feeds to veal calves: II. Behavior, physiology, and abomasal damage. J Anim Sci 80:367–375
Maul R, Warth B, Kant JS, Schebb NH, Krska R, Koch M, Sulyok M (2012) Investigation of the hepatic glucuronidation pattern of the Fusarium mycotoxin deoxynivalenol in various species. Chem Res Toxicol 25(12):2715–2717
Mikami O, Yamamoto S, Yamanaka N, Nakajima Y (2004) Porcine hepatocyte apoptosis and reduction of albumin secretion induced by deoxynivalenol. Toxicology 204:241–249
Monbaliu S, Van Poucke C, Detavernier C, Dumoulin F, Van De Velde M, Schoeters E, Van Dyck S, Averkieva O, Van Peteghem C, De Saeger S (2010) Occurrence of mycotoxins in feed as analyzed by a multi-mycotoxin LC–MS/MS method. J Agr Food Chem 58:66–71
Pardon B, Catry B, Boone R, Theys H, De Bleecker K, Dewulf J, Deprez P (2014) Characteristics and challenges of the modern Belgian veal industry. Vlaams Diergen Tijds 83:155–163
Payros D, Alassane-Kpembi I, Pierron A, Loiseau N, Pinton P, Oswald IP (2016) Toxicology of deoxynivalenol and its acetylated and modified forms. Arch Toxicol 90:2931–2957
Pestka JJ, Smolinski AT (2005) Deoxynivalenol: toxicology and potential effects on humans. J Toxicol Environ Health B 8:39–69
Pinton P, Oswald IP (2014) Effect of deoxynivalenol and other type B trichothecenes on the intestine: a review. Toxins 6:1615–1643
Prelusky DB, Veira DM, Trenholm HL (1985) Plasma pharmacokinetics of the mycotoxin deoxynivalenol following oral and intravenous administration to sheep. J Environ Sci Heal B 20:603–624
Prelusky DB, Hartin KE, Trenholm HL, Miller JD (1988) Pharmacokinetic fate of 14C-labeled deoxynivalenol in swine. Fundam Appl Toxicol 10:276–286
Ronzoni A, Bayrou C, Evrard L, Touati K, Sartelet A (2013) Hepatocholecystitis due to Salmonella Dublin in a crossbred calf. 1st Farah Day, Liège, Belgium (October 17, 2014)
Saint-Cyr MJ, Perrin-Guyomard A, Manceau J, Houée P, Delmas JM, Rolland JG, Laurentie M (2015) Risk assessment of deoxynivalenol by revisiting its bioavailability in pig and rat models to establish which is more suitable. Toxins 7:5167–5181
Schatzmayr G, Streit E (2013) Global occurrence of mycotoxins in the food and feed chain: facts and figures. World Mycotoxin J 6:213–222
Schwartz-Zimmermann HE, Hametner C, Nagl V, Slavik V, Moll WD, Berthiller F (2014) Deoxynivalenol (DON) sulfonates as major DON metabolites in rats: from identification to biomarker method development, validation and application. Anal Bioanal Chem 406:7911–7924
Schwartz-Zimmermann HE, Fruhmann P, Dänicke S, Wiesenberger G, Caha S, Weber J, Berthiller F (2015) Metabolism of deoxynivalenol and deepoxy-deoxynivalenol in broiler chickens, pullets, roosters and turkeys. Toxins 7:4706–4729
Schwartz-Zimmermann HE, Hametner C, Nagl V, Fiby I, Macheiner L, Winkler J, Dänicke S, Clark E, Pestka JJ, Berthiller F (2017) Glucuronidation of deoxynivalenol (DON) by different animal species: identification of iso-DON glucuronides and iso-deepoxy-DON glucuronides as novel DON metabolites in pigs, rats, mice, and cows. Arch Toxicol 91:3857–3872
Seeling K, Dänicke S, Valenta H, van Egmond HP, Schothorst RC, Jekel AA, Lebzien P, Schollenberger M, Razzazi-Fazeli E, Flachowsky G (2006) Effects of Fusarium toxin-contaminated wheat and feed intake level of the biotransformation and carry-over of deoxynivalenol in dairy cows. Food Addit Contam 23:1008–1020
Smith BP, Magdesian KG (2009) Alterations in alimentary and hepatic function. In: Smith BP (ed) Large animal internal medicine, 4th edn. Mosby Elsevier, Davis, pp 96–116
Smith MC, Madec S, Coton E, Hymery N (2016) Natural co-occurrence of mycotoxins in foods and feeds and their in vitro combined toxicological effects. Toxins 8:94
Thompson WL, Wannemacher RW (1986) Structure-function-relationships of 12,13-epoxytrichothecene mycotoxins in cell-culture comparison to whole animal lethality. Toxicon 24:985–994
Thompson M, Ellison SL, Wood R (2002) Harmonized guidelines for single-laboratory validation of methods of analysis (IUPAC Technical Report). Pure Appl Chem 74:835–855
Turner PC, White KL, Burley VJ, Hopton RP, Rajendram A, Fisher J, Cade JE, Wild CP (2010) A comparison of deoxynivalenol intake and urinary deoxynivalenol in UK adults. Biomarkers 15:553–562
Van Bost S, Roels S, Mainil J (2001) Necrotoxigenic Escherichia coli type-2 invade and cause diarrhoea during experimental infection in colostrum-restricted newborn calves. Vet Microbiol 8:315–329
Van Asselt ED, Azambuja W, Moretti A, Kastelein P, De Rijk TC, Stratakou I, Van Der Fels-Klerx HJ (2012) A Dutch field survey on fungal infection and mycotoxin concentrations in maize. Food Addit Contam Part A 29:1556–1565
Van Limbergen T, Devreese M, Croubels S, Broekaert N, Michiels A, De Saeger S, Maes D (2017) Role of mycotoxins in herds with and without problems with tail necrosis in neonatal pigs. Vet Rec 181:539
VICH GL 49 (2011) Studies to evaluate the metabolism and residue kinetics of veterinary drugs in food producing animals: validation of analytical methods used in residue depletion studies. http://www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/UCM207942.pdf. Accessed 1 Mar 2015
Wan D, Huang L, Pan Y, Wu Q, Chen D, Tao Y, Wang X, Liu Z, Li J, Wang L, Yuan Z (2014) Metabolism, distribution, and excretion of deoxynivalenol with combined techniques of radiotracing, high-performance liquid chromatography ion trap time-of-flight mass spectrometry, and online radiometric detection. J Agric Food Chem 62:288–296
Warth B, Sulyok M, Fruhmann P, Berthiller F, Schuhmacher R, Hametner C, Adam G, Fröhlich J, Krska R (2012) Assessment of human deoxynivalenol exposure using an LC–MS/MS based biomarker method. Toxicol Lett 211:85–90
Webb LE, van Reenen C, Berends H, Engel B, de Boer IJM, Gerrits WJJ, Bokkers EAM (2015) The role of solid feed amount and composition and of milk replacer supply in veal calf welfare. J Dairy Sci 98:5467–5481
Winkler J, Kersten S, Valenta H, Hüther L, Meyer U, Engelhardt U, Dänicke S (2014) Simultaneous determination of zearalenone, deoxynivalenol and their metabolites in bovine urine as biomarkers of exposure. World Mycotoxin J 8:63–74
Yoshizawa T, Cote LM, Swanson SP, Buck WB (1986) Confirmation of DOM-1, a de-epoxidation metabolite of deoxynivalenol, in biological-fluids of lactating cows. Agric Biol Chem 50:227–222
Zhang J, Shi H, Wang Y, Li S, Zhang H, Cao Z, Yang K (2018) Effects of limit-feeding diets with different forage-to-concentrate ratios on nutrient intake, rumination, ruminal fermentation, digestibility, blood parameters and growth in Holstein heifers. Anim Sci J 89:527–536
