Pfohl-Leszkowicz A, Hadjeba-Medjdoub K, Ballet N, Schrickx J, Fink-Gremmels J
a Department Bioprocess & Microbial System , University of Toulouse, INPT, ENSAT, Laboratory Chemical Engineering, UMR-CNRS 5503 , Auzeville-Tolosane , France.
Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2015;32(4):604-16. doi: 10.1080/19440049.2014.970590. Epub 2014 Nov 13.
The aim of this paper was to evaluate the capacity of several yeast-based products, derived from baker's and brewer's yeasts, to sequester the mycotoxin ochratoxin A (OTA) and to decrease its rate of absorption and DNA adduct formation in vivo. The experimental protocol included in vitro binding studies using isotherm models, in vivo chicken experiments, in which the serum and tissue concentrations of OTA were analysed in the absence and presence of the test compounds, and the profile of OTA-derived metabolites and their associated DNA adducts were determined. Additionally in vitro cell culture studies (HK2 cells) were applied to assess further the effects for yeast cell product enriched with glutathione (GSH) or selenium. Results of the in vitro binding assay in a buffer system indicated the ability of the yeast-based products, as sequester of OTA, albeit at a different level. In the in vitro experiments in chickens, decreased serum and tissue concentrations of treated animals confirmed that yeast-based products are able to prevent the absorption of OTA. A comparison of the binding affinity in a standard in vitro binding assay with the results obtained in an in vivo chicken experiment, however, showed a poor correlation and resulted in a different ranking of the products. More importantly, we could show that yeast-based products actively modulate the biotransformation of OTA in vivo as well as in vitro in a cell culture model. This effect seems to be attributable to residual enzymatic activities in the yeast-based products. An enrichment of yeast cell wall products with GSH or selenium further modulated the profile of the generated OTA metabolites and the associated pattern of OTA-induced DNA adducts by increasing the conversion of OTA into less toxic metabolites such as OTA, OTB and 4-OH-OTA. A reduced absorption and DNA adduct formation was particularly observed with GSH-enriched yeast, whereas selenium-enriched yeasts could counteract the OTA-induced decrease in cell viability, but at the same time increased the OTA-DNA adducts formation. These findings indicate the need for an in-depth characterisation of yeast-based products used as mycotoxin-mitigating feed additives, in in vivo models with target animal species taking into account not only their ability to sequester toxins in the gastrointestinal tract but also their potential effects on the biotransformation of mycotoxins.
本文旨在评估几种源自面包酵母和酿酒酵母的酵母基产品螯合霉菌毒素赭曲霉毒素A（OTA）以及降低其体内吸收速率和DNA加合物形成的能力。实验方案包括使用等温模型的体外结合研究、体内鸡实验（在有无受试化合物的情况下分析OTA的血清和组织浓度，并确定OTA衍生代谢物及其相关DNA加合物的概况），此外还进行了体外细胞培养研究（HK2细胞）以进一步评估富含谷胱甘肽（GSH）或硒的酵母细胞产品的效果。缓冲体系中的体外结合试验结果表明，酵母基产品具有作为OTA螯合剂的能力，尽管程度不同。在鸡的体外实验中，受试动物血清和组织中OTA浓度降低证实了酵母基产品能够防止OTA的吸收。然而，将标准体外结合试验中的结合亲和力与体内鸡实验结果进行比较时，发现相关性较差，且产品排名不同。更重要的是，我们能够证明酵母基产品在体内以及细胞培养模型中均能积极调节OTA的生物转化。这种效应似乎归因于酵母基产品中的残留酶活性。用GSH或硒富集酵母细胞壁产品，通过增加OTA向毒性较小的代谢物（如OTA、OTB和4-OH-OTA）的转化，进一步调节了生成的OTA代谢物概况以及OTA诱导的DNA加合物相关模式。特别在富含GSH的酵母中观察到吸收和DNA加合物形成减少，而富含硒的酵母可以抵消OTA诱导的细胞活力下降，但同时增加了OTA-DNA加合物的形成。这些发现表明，在针对目标动物物种的体内模型中，需要深入表征用作霉菌毒素缓解饲料添加剂的酵母基产品，不仅要考虑它们在胃肠道中螯合毒素的能力，还要考虑它们对霉菌毒素生物转化的潜在影响。
