Toxicological interactions between the mycotoxins deoxynivalenol, nivalenol and their acetylated derivatives in intestinal epithelial cells

Toxicological interactions between the mycotoxins deoxynivalenol, nivalenol and their acetylated derivatives in intestinal epithelial cells
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DOI:
10.1007/s00204-014-1309-4
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发表时间:
2015-08-01
影响因子:
6.1
通讯作者:
Oswald, Isabelle P.
Oswald, Isabelle P.
中科院分区:
医学2区
文献类型:
--
作者:
Alassane-Kpembi, Imourana;Puel, Olivier;Oswald, Isabelle P.

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在霉菌毒素污染的情况下,食品和饲料通常被一种以上的毒素污染。然而,关于霉菌毒素组合影响的毒理学数据很少。肠上皮是抵抗食物污染物的第一道屏障,这个不断更新的器官对霉菌毒素特别敏感。本研究旨在研究脱氧雪腐镰刀菌烯醇(DON)和其他四种B型雪腐镰刀菌烯(TCT B)、3-乙酰脱氧雪腐镰刀菌烯醇(3-ADON)、15-乙酰脱氧雪腐镰刀菌烯醇(15-ADON)、雪腐镰刀菌烯醇(NIV)和镰孢镰刀菌酮-X(FX)单独或联合应用对肠上皮细胞的作用。使增殖的、未转化的IPEC-1细胞暴露于增加剂量的单独或二元混合物的TCTB,并用MTT试验测量真菌毒素诱导的细胞毒性。采用等效线-联合指数法评估毒理学相互作用。测试的五种真菌毒素及其混合物对增殖的肠细胞具有剂量依赖性影响。DON-NIV、DON-15-ADON和15-ADON-3-ADON组合具有协同作用,10%细胞毒性的协同作用强度范围为2至7。DON和3-ADON之间的关联也显示出协同作用,但仅在高剂量下,在较低剂量下注意到拮抗作用。NIV与FX之间存在相加作用,DON与FX之间存在拮抗作用。这些结果表明,食品和饮食中同时存在真菌毒素可能比单独使用真菌毒素预测的毒性更大。考虑到饮食中TCTB的频繁共存,应考虑这种协同作用。
In case of mycotoxin contaminations, food and feedstuff are usually contaminated by more than one toxin. However toxicological data concerning the effects of mycotoxin combinations are sparse. The intestinal epithelium is the first barrier against food contaminants and this constantly renewing organ is particularly sensitive to mycotoxins. The aim of this study was to investigate the effects of deoxynivalenol (DON) and four other type B trichothecenes (TCTB), 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), nivalenol (NIV) and fusarenon-X (FX) alone or in combination on intestinal epithelial cells. Proliferating, non-transformed IPEC-1 cells were exposed to increasing doses of TCTB, alone or in binary mixtures and mycotoxin-induced cytotoxicity was measured with MTT test. The toxicological interactions were assessed using the isobologram-Combination index method. The five tested mycotoxins and their mixtures had a dose-dependent effect on the proliferating enterocytes. DON-NIV, DON-15-ADON and 15-ADON-3-ADON combinations were synergistic, with magnitude of synergy for 10 % cytotoxicity ranging from 2 to 7. The association between DON and 3-ADON also demonstrated a synergy but only at high doses, at lower doses antagonism was noted. Additivity was observed between NIV and FX, and antagonism between DON and FX. These results indicate that the simultaneous presence of mycotoxins in food commodities and diet may be more toxic than predicted from the mycotoxins alone. This synergy should be taken into account considering the frequent co-occurrence of TCTB in the diet.