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极低水平的脱氧雪腐镰刀菌烯醇和伏马毒素B1单独或联合经口给予小鼠7天后诱导的脂质代谢紊乱、淋巴细胞死亡和肾毒性。

Lipid metabolism disorders, lymphocytes cells death, and renal toxicity induced by very low levels of deoxynivalenol and fumonisin b1 alone or in combination following 7 days oral administration to mice.

作者信息

Kouadio J H, Moukha S, Brou K, Gnakri D

机构信息

Department of Biochemistry and Microbiology, University of Daloa, Ivoiry Coast, France ; Department of Food Technologies and Sciences, University of Nangui Abrogoua, Abidjan, Ivoiry Coast, France.

UPR 1264- MycSA, National Institute for Agricultural Research, Research Center of Bordeaux, Aquitaine, France.

出版信息

Toxicol Int. 2013 Sep;20(3):218-23. doi: 10.4103/0971-6580.121673.

Abstract

SCOPE

In our previous study focused on in vitro interactive effect of Fusarium mycotoxins deoxynivalenol (DON) and fumonisin B1 (FB1), we reported that these toxins tested at low level and in association could lead to additive or synergistic cytotoxic effect. The aim of the present study is to confirm those findings by in vivo study.

MATERIALS AND METHODS

Swiss mice were orally administered with low doses of DON (45 μg/kg bw/day), FB1 (110 μg/kg bw/day), and their mixture (DON + FB1) for 7 days.

RESULTS

As results, no death or abnormal symptoms were observed in all groups. The significant of loss of weight was observed in females group treated with FB1 and its association with DON. Serum chemistry examinations revealed that disorders in lipid metabolism, renal filtration perturb and a rhabdomyolysis. DON has been found as particular inducer of kidney cell deoxyribonucleic acid (DNA) methylation and blood lymphocytes cell death as measured by lymphocytes DNA fragmentation. Female mice were more sensitive and the mixture of DON and FB1 led to additive or more than additive effect particularly for their target kidney which showed different pattern of toxicity.

CONCLUSION

Based on the results of this study, the no-observed-adverse effect level (NOAEL) o both DON and FB1 should be low than 45 μg/kg bw/day and 110 μg/kg bw/day, respectively in mice.

摘要

范围

在我们之前关注镰刀菌霉菌毒素脱氧雪腐镰刀菌烯醇(DON)和伏马菌素B1(FB1)体外相互作用效应的研究中,我们报告称,这些低水平测试且联合使用的毒素可能会导致相加或协同的细胞毒性效应。本研究的目的是通过体内研究来证实这些发现。

材料与方法

给瑞士小鼠口服低剂量的DON(45微克/千克体重/天)、FB1(110微克/千克体重/天)及其混合物(DON + FB1),持续7天。

结果

结果显示,所有组均未观察到死亡或异常症状。在接受FB1及其与DON联合处理的雌性组中观察到显著的体重减轻。血清化学检查显示脂质代谢紊乱、肾滤过功能紊乱和横纹肌溶解。通过淋巴细胞DNA片段化检测发现,DON是肾细胞脱氧核糖核酸(DNA)甲基化和血液淋巴细胞死亡的特殊诱导剂。雌性小鼠更敏感,DON和FB1的混合物导致相加或超过相加的效应,特别是对其靶器官肾脏,显示出不同的毒性模式。

结论

基于本研究结果,在小鼠中,DON和FB1的未观察到有害作用水平(NOAEL)应分别低于45微克/千克体重/天和110微克/千克体重/天。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/354b/3877489/f90913351541/TI-20-218-g005.jpg

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