title: Assessment and characterisation of yeast-based products intended to mitigate ochratoxin exposure using in vitro and in vivo models.
abstract: 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.
authors.affiliation: a Department Bioprocess & Microbial System , University of Toulouse, INPT, ENSAT, Laboratory Chemical Engineering, UMR-CNRS 5503 , Auzeville-Tolosane , France.
authors.forename: A
authors.initials: A
authors.lastname: Pfohl-Leszkowicz
authors.forename: K
authors.initials: K
authors.lastname: Hadjeba-Medjdoub
authors.forename: N
authors.initials: N
authors.lastname: Ballet
authors.forename: J
authors.initials: J
authors.lastname: Schrickx
authors.forename: J
authors.initials: J
authors.lastname: Fink-Gremmels
mesh_terms: D000821:Animal Feed / Q000382:microbiology; D000818:Animals; D001711:Biotransformation; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002645:Chickens; D018736:DNA Adducts; D004249:DNA Damage / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006799:Housing, Animal; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D009793:Ochratoxins / Q000097:blood*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D012645:Selenomethionine / Q000378:metabolism
chemical_list: D018736:DNA Adducts; D009793:Ochratoxins; C025589:ochratoxin A; D012645:Selenomethionine; D005978:Glutathione
keywords: cell culture; detoxification; ochratoxin A; poultry; yeast-based product