title: Effects of deoxynivalenol (DON), zearalenone (ZEN), and related metabolites on equine peripheral blood mononuclear cells (PBMC) in vitro and background occurrence of these toxins in horses.
abstract: Both deoxynivalenol (DON), zearalenone (ZEN), and their metabolites are known to modulate immune cells in various species whereby viability and proliferation are influenced. Such effects were rarely examined in horses. Therefore, one aim of the present study was to titrate the inhibitory concentrations of DON, 3-acetyl-DON (3AcDON), de-epoxy-DON (DOM-1), ZEN, and α- and β-zearalenol (ZEL) at which viability and proliferation of equine PBMC were reduced by 50 % (IC50) and 10 % (IC10) in vitro. For evaluation of practical relevance of the in vitro findings, a further aim was to screen horses for the background occurrence of DON, ZEN, and their metabolites in systemic circulation and to relate toxin residues both to the inhibitory toxin concentrations and to hematological and clinical-chemical characteristics.The IC50 (μM) for DON, 3AcDON, β-ZEL, α-ZEL, and ZEN were determined at 3.09, 25.90, 75.44, 97.44, and 98.15 in unstimulated cells, respectively, while in proliferating cells, the corresponding IC50 values were 0.73, 6.89, 45.16, 75.96, and 82.51. Neither viability nor proliferation was influenced by DOM-1 up to a concentration of 100 μM.The in vivo screening (N = 49) revealed the occurrence of ZEN (N = 24), α-ZEL (N = 3), β-ZEL (N = 37), DON, and DOM-1 (N = 2). The detected concentrations were much lower than the corresponding IC50 while the IC10 of DON and β-ZEL for proliferating PBMC corresponded to approximately 26 and 35 ng/mL which might be relevant when contaminated diets are fed.Clinical-chemical and hematological traits were not related to mycotoxin residue levels excepting blood urea nitrogen which was positively correlated to the sum of β-ZEL, α-ZEL, and ZEN concentration. Whether this reflects simply the feeding history of the horses or renal failures giving rise to a prolonged half-life of the toxins needs to be clarified further.
authors.affiliation: Horse Clinic Barkhof, Sottrum, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Schumann
authors.affiliation: Institute of Animal Nutrition, Friedrich-Loeffler-Institute (FLI), Federal Research Institute for Animal Health, Braunschweig, Germany.
authors.forename: Janine
authors.initials: J
authors.lastname: Winkler
authors.affiliation: Institute of Animal Nutrition, Friedrich-Loeffler-Institute (FLI), Federal Research Institute for Animal Health, Braunschweig, Germany.
authors.forename: Nicola
authors.initials: N
authors.lastname: Mickenautsch
authors.affiliation: Horse Clinic of the University of Veterinary Medicine Hannover, Hanover, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Warnken
authors.affiliation: Institute of Animal Nutrition, Friedrich-Loeffler-Institute (FLI), Federal Research Institute for Animal Health, Braunschweig, Germany. sven.daenicke@fli.bund.de.
authors.forename: Sven
authors.initials: S
authors.lastname: Dänicke
mesh_terms: D000818:Animals; D001774:Blood Chemical Analysis; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006736:Horses; D020128:Inhibitory Concentration 50; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D014255:Trichothecenes / Q000097:blood* / Q000633:toxicity*; D015025:Zearalenone / Q000097:blood* / Q000633:toxicity*
chemical_list: D014255:Trichothecenes; D015025:Zearalenone; C007262:deoxynivalenol
keywords: Deoxynivalenol; Horse; Immune cells; Zearalenones