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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

机译:体外脱氧雪腐烯醇(DON),玉米赤霉烯酮(ZEN)和相关代谢产物对马外周血单个核细胞(PBMC)的影响以及这些毒素在马中的产生背景

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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 a- and |3-zearalenol (ZEL) at which viability and proliferation of equine PBMC were reduced by 50 % (IC5o) and 10 % (IC_0) 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 concentrationsand to hematological and clinical-chemical characteristics.The IC_(50) (uM) for DON, 3AcDON, 3-ZEL, cc-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 IC_(50) 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 uM.The in vivo screening (N= 49) revealed the occurrence of ZEN (N=2A), a-ZEL (N=3), (3-ZEL (N=37), DON, and DOM-1 (N=2). The detected concentrations were much lower than the corresponding IC50 while the ICi0 of DON and (3-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 (3-ZEL, a-ZEL, and ZEN concentration. Whether this reflects simply the feeding history ofthe horses or renal failures giving rise to a prolonged half-life of the toxins needs to be clarified further.
机译:已知脱氧雪腐烯醇(DON),玉米赤霉烯酮(ZEN)及其代谢物均可调节各种物种中的免疫细胞,从而影响生存力和增殖。在马中很少检查到这种效果。因此,本研究的目的是滴定DON,3-乙酰基DON(3AcDON),脱环氧DON(DOM-1),ZEN以及α-和| 3-玉米赤霉烯醇(ZEL)的抑制浓度。在体外,马PBMC的活力和增殖降低了50%(IC50)和10%(IC_0)。为了评估体外发现的实际相关性,进一步的目的是筛选马体内DON,ZEN及其代谢物在体循环中的背景发生情况,并将毒素残留与抑制毒素浓度以及血液学和临床化学联系起来在未经刺激的细胞中,DON,3AcDON,3-ZEL,cc-ZEL和ZEN的IC_(50)(uM)分别为3.09、25.90、75.44、97.44和98.15。相应的IC_(50)值为0.73、6.89、45.16、75.96和82.51.DOM-1浓度至100 uM都没有影响生存力和增殖。体内筛选(N = 49)显示ZEN的发生。 (N = 2A),a-ZEL(N = 3),(3-ZEL(N = 37),DON和DOM-1(N = 2)。检测到的浓度远低于相应的IC50,而ICi0 DON和(3-ZEL用于增生PBMC的浓度)分别约为26和35 ng / mL,当受污染时d除了血液尿素氮与(3-ZEL,α-ZEL和ZEN浓度之和呈正相关)外,临床化学和血液学特征与霉菌毒素残留水平无关。这是否仅反映了马的摄食史或导致毒素半衰期延长的肾功能衰竭,尚需进一步阐明。

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