Abstract
This study aimed to investigate a potential modulatory effect of E. coli lipopolysaccharide (LPS) on the kinetics of deoxynivalenol (DON) and zearalenone (ZEN) after pre- or post-hepatic LPS administration to unravel the putative role of the liver. Fifteen barrows were fed a diet containing mycotoxin-contaminated maize (4.59 mg DON/kg feed, 0.22 mg ZEN/kg feed) for 29 days and equipped with pre-hepatic catheters (portal vein, “po”) and post-hepatic catheters (jugular vein, “ju”), facilitating simultaneous infusion of LPS (“LPS group”, 7.5 μg/kg body weight) or 0.9% sterile NaCl solution (control, “CON group”, equivolumar to LPS group) and blood sampling. This resulted in three infusion groups, depending on infusion site: CONju-CONpo, CONju-LPSpo, and LPSju-CONpo. On day 29, pigs were fed their morning ration (700 g/pig) (−15 min), and blood samples were collected at regular intervals relative to infusion start. At 195 min, pigs were sacrificed and bile, urine, liquor, and liver samples collected. DON concentrations in jugular and portal blood decreased in both LPS-infused groups, whereas the ZEN concentrations increased, regardless of the treatment site. In liver tissue, a decrease of both toxin concentrations was observed in endotoxaemic pigs as well as a drop in hepatic conjugation, regardless of LPS entry site. In contrast to our hypothesis, DON and ZEN were not differently altered depending on the LPS-entry site. Neither the absorption nor the accumulation of DON and ZEN in different tissues differed significantly between animals which were infused with LPS via either the jugular or portal vein.
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References
Angus DC, van der Poll T (2013) Severe sepsis and septic shock. N Engl J Med 369:2063
Avantaggiato G, Havenaar R, Visconti A (2004) Evaluation of the intestinal absorption of deoxynivalenol and nivalenol by an in vitro gastrointestinal model, and the binding efficacy of activated carbon and other adsorbent materials. Food Chem Toxicol 42:817–824
Banhegyi G, Mucha I, Garzo T, Antoni F, Mandl J (1995) Endotoxin inhibits Glucuronidation in the liver - an effect mediated by intercellular communication. Biochem Pharmacol 49:65–68
Banks WA, Erickson MA (2010) The blood-brain barrier and immune function and dysfunction. Neurobiol Dis 37:26–32
Bannert E, Tesch T, Kluess J, Frahm J, Kersten S, Kahlert S, Renner L, Rothkötter HJ, Dänicke S (2015) Metabolic and hematological consequences of dietary Deoxynivalenol interacting with systemic Escherichia coli lipopolysaccharide. Toxins 7:4773–4796
Biehl ML, Prelusky DB, Koritz GD, Hartin KE, Buck WB, Trenholm HL (1993) Biliary excretion and enterohepatic cycling of zearalenone in immature pigs. Toxicol Appl Pharmacol 121:152–159
Brezina U, Rempe I, Kersten S, Valenta H, Humpf HU, Dänicke S (2014a) Diagnosis of intoxications of piglets fed with Fusarium toxin-contaminated maize by the analysis of mycotoxin residues in serum, liquor and urine with LC-MS/MS. Arch Anim Nutr 68:425–447
Brezina U, Valenta H, Rempe I, Kersten S, Humpf HU, Dänicke S (2014b) Development of a liquid chromatography tandem mass spectrometry method for the simultaneous determination of zearalenone, deoxynivalenol and their metabolites in pig serum. Mycotoxin Res 30:171–186
Brezina U, Rempe I, Kersten S, Valenta H, Humpf HU, Dänicke S (2016) Determination of zearalenone, deoxynivalenol and metabolites in bile of piglets fed diets with graded levels of Fusarium toxin contaminated maize. World Mycotoxin J 9:179–193
Burdon D, Zabel P (2002) Acute phase reaction and immunocompetence in sepsis and SIRS. Wien Klin Wochenschr 114(Suppl 1):1–8
Cinel I, Dellinger RP (2007) Advances in pathogenesis and management of sepsis. Curr Opin Infect Dis 20:345–352
Coppock RW, Swanson SP, Gelberg HB, Koritz GD, Hoffman WE, Buck WB, Vesonder RF (1985) Preliminary-study of the pharmacokinetics and Toxicopathy of Deoxynivalenol (Vomitoxin) in Swine. Am J Vet Res 46:169–174
Cullen JJ, Caropreso DK, Ephgrave KS (1995) Effect of endotoxin on canine gastrointestinal motility and transit. J Surg Res 58:90–95
Cullen JJ, Ephgrave KS, Caropreso DK (1996) Gastrointestinal myoelectric activity during endotoxemia. Am J Surg 171:596–599
Dänicke S, Brezina U (2013) Kinetics and metabolism of the Fusarium toxin deoxynivalenol in farm animals: consequences for diagnosis of exposure and intoxication and carry over. Food Chem Toxicol 60:58–75
Dänicke S, Winkler J (2015) Invited review: diagnosis of zearalenone (ZEN) exposure of farm animals and transfer of its residues into edible tissues (carry over). Food Chem Toxicol 84:225–249
Dänicke S, Valenta H, Döll S (2004) On the toxicokinetics and the metabolism of deoxynivalenol (DON) in the pig. Arch Anim Nutr 58:169–180
Dänicke S, Swiech E, Buraczewska L, Ueberschar KH (2005) Kinetics and metabolism of zearalenone in young female pigs. J Anim Physiol Anim Nutr 89:268–276
Dänicke S, Beyer M, Breves G, Valenta H, Humpf HU (2010) Effects of oral exposure of pigs to deoxynivalenol (DON) sulfonate (DONS) as the non-toxic derivative of DON on tissue residues of DON and de-epoxy-DON and on DONS blood levels. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 27:1558–1565
Dänicke S, Valenta H, Ganter M, Brosig B, Kersten S, Diesing AK, Kahlert S, Panther P, Kluess J, Rothkötter HJ (2014) Lipopolysaccharides (LPS) modulate the metabolism of deoxynivalenol (DON) in the pig. Mycotoxin Res 30:161–170
Döll S, Dänicke S (2011) The Fusarium toxins deoxynivalenol (DON) and zearalenone (ZON) in animal feeding. Prev Vet Med 102:132–145
Döll S, Dänicke S, Ueberschär KH, Valenta H, Schnurrbusch U, Ganter M, Klobasa F, Flachowsky G (2003) Effects of graded levels of Fusarium toxin contaminated maize in diets for female weaned piglets. Arch Anim Nutr 57:311–334
Eriksen GS, Pettersson H, Johnsen K, Lindberg JE (2002) Transformation of trichothecenes in ileal digesta and faeces from pigs. Arch Anim Nutr 56:263–274
Eskandari MK, Kalff JC, Billiar TR, Lee KKW, Bauer AJ (1997) Lipopolysaccharide activates the muscularis macrophage network and suppresses circular smooth muscle activity. Am J Phys 273:G727–G734
Geier A, Fickert P, Trauner M (2006) Mechanisms of disease: mechanisms and clinical implications of cholestasis in sepsis. Nat Clin Pract Gastroenterol Hepatol 3:574–585
Goyarts T, Dänicke S (2006) Bioavailability of the Fusarium toxin deoxynivalenol (DON) from naturally contaminated wheat for the pig. Toxicol Lett 163:171–182
Jandacek RJ (1982) The effect of nonabsorbable lipids on the intestinal absorption of lipophiles. Drug Metab Rev 13:695–714
Lippelt M, Valenta H, Winkler J, Dänicke S (2014) Entwicklung einer Probenaufarbeitungsmethode zur Bestimmung von Zearalenon und Deoxynivalenol sowie deren Metaboliten in Leber mittels LC-ESI-MS/MS. TU Braunschweig, Germany
Malekinejad H, Maas-Bakker R, Fink-Gremmels J (2006) Species differences in the hepatic biotransformation of zearalenone. Vet J 172:96–102
Oldenburg E, Bramm A, Valenta H (2007) Influence of nitrogen fertilization on deoxynivalenol contamination of winter wheat - experimental field trials and evaluation of analytical methods. Mycotoxin Res 23:7–12
Olsen M, Malmlof K, Pettersson H, Sandholm K, Kiessling KH (1985) Plasma and urinary levels of Zearalenone and alpha-Zearalenol in a Prepubertal gilt fed Zearalenone. Acta Pharmacol Toxicol (Copenh) 56:239–243
Pestka JJ (2007) Deoxynivalenol: toxicity, mechanisms and animal health risks. Anim Feed Sci Technol 137:283–298
Pluske JR, Pethick DW, Hopwood DE, Hampson DJ (2002) Nutritional influences on some major enteric bacterial diseases of pigs. Nutr Res Rev 15:333–371
Prelusky DB, Hartin KE, Trenholm HL, Miller JD (1988) Pharmacokinetic fate of C-14-labeled Deoxynivalenol in Swine. Fundam Appl Toxicol 10:276–286
Prelusky DB, Hartin KE, Trenholm HL (1990) Distribution of Deoxynivalenol in cerebral spinal-fluid following administration to Swine and sheep. J Environ Sci Health B 25:395–413
Renner L, Kahlert S, Tesch T, Bannert E, Frahm J, Böszörményi AB, Kluess J, Kersten S, Schönfeld P, Rothkötter HJ, Dänicke S (2017) Chronic DON exposure and acute LPS challenge: consequences on porcine liver morphology and function. Mycotoxin Res. doi:10.1007/s12550-017-0279-9
Shin BS, Hong SH, Bulitta JB, Lee JB, Hwang SW, Kim HJ, Yang SD, Yoon HS, Kim DJ, Lee BM, Yoo SD (2009) Physiologically based pharmacokinetics of zearalenone. J Toxicol Environ Health A 72:1395–1405
Sobrova P, Adam V, Vasatkova A, Beklova M, Zeman L, Kizek R (2010) Deoxynivalenol and its toxicity. Interdiscip Toxicol 3:94–99
Tesch T, Bannert E, Kluess J, Frahm J, Kersten S, Breves G, Renner L, Kahlert S, Rothkötter, HJ, Dänicke S (2016) Does dietary deoxynivalenol modulate the acute phase reaction in endotoxaemic pigs?-Lessons from clinical signs, white blood cell counts, and TNF-Alpha. Toxins 8. doi:10.3390/toxins8010003
VDLUFA (2006) VDLUFA-Methodenbuch III. 6. Ergänzung 2006, Zearalenon 16.9.2. VDLUFA-Verlag, Darmstadt
Wilson R, Ziprin R, Ragsdale S, Busbee D (1985) Uptake and vascular transport of ingested aflatoxin. Toxicol Lett 29:169–176
Winkler J, Kersten S, Valenta H, Huether L, Meyer U, Engelhardt U, Dänicke S (2015) Simultaneous determination of zearalenone, deoxynivalenol and their metabolites in bovine urine as biomarkers of exposure. World Mycotox J 8:63–74
Wirthlin DJ, Cullen JJ, Spates ST, Conklin JL, Murray J, Caropreso DK, Ephgrave KS (1996) Gastrointestinal transit during endotoxemia: the role of nitric oxide. J Surg Res 60:307–311
Wu F, Munkvold GP (2008) Mycotoxins in ethanol co-products: modeling economic impacts on the livestock industry and management strategies. J Agric Food Chem 56:3900–3911
Wyns H, Plessers E, De Backer P, Meyer E, Croubels S (2015) In vivo porcine lipopolysaccharide inflammation models to study immunomodulation of drugs. Vet Immunol Immunopathol 166:58–69
Zimmerman JJ, Karriker LA, Ramirez A, Schwartz KJ, Stevenson GW (2012) Diseases of Swine. 10th edn. Wiley-Blackwell. ISBN 978–0–8138-2267-9
Zinedine A, Soriano JM, Molto JC, Manes J (2007) Review on the toxicity, occurrence, metabolism, detoxification, regulations and intake of zearalenone: an oestrogenic mycotoxin. Food Chem Toxicol 45:1–18
Acknowledgements
This study was financially supported by Deutsche Forschungsgemeinschaft (DFG DA 558/1-4). The authors would like to thank Beate Fulge and Dr. Liane Hüther for sample preparation and analysis. Furthermore, the authors gratefully acknowledge Melanie Schären for critical language editing of the manuscript.
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Bannert, E., Tesch, T., Kluess, J. et al. Plasma kinetics and matrix residues of deoxynivalenol (DON) and zearalenone (ZEN) are altered in endotoxaemic pigs independent of LPS entry site. Mycotoxin Res 33, 183–195 (2017). https://doi.org/10.1007/s12550-017-0276-z
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DOI: https://doi.org/10.1007/s12550-017-0276-z