Mycotoxin contaminations in feed and food are a widely known threat. Not only can they have direct repercussions on animal and human health, but they can also interact with other xenobiotic substances such as drugs. In 2022, Lootens et al. established a review to better understand this mechanism. Mycotoxins—as every xenobiotic – undergo absorption, distribution, metabolism, and excretion (ADME).
Their metabolism is mainly assured by hepatic enzymes from the CYP450 complex, which is also the case for approximately 80% of drugs. Different types of drugs and mycotoxins can be CYP450 inducers or inhibitors. Inducers lead to more metabolite formation, which is satisfactory in case of detoxification, but not in case of bioactivation (e.g., AFB1 conversion into AFBO, exerting carcinogenicity). Inhibitors lead to less metabolite formation.
It is more likely that drugs will have an impact on the pharmacokinetics of mycotoxins than mycotoxins will impact drug disposition, considering their respective concentrations of exposure. Another type of interaction occurs when there is a structural similarity between the mycotoxin and the drug. For example, in the presence of a mycotoxin possessing an azole structure, an azole antifungal drug may interact with the mycotoxin instead of interacting with the targeted fungi.
Last, the disruption of the intestinal barrier caused by cytotoxic mycotoxins like T-2 toxin also impact the pharmacodynamic of certain drugs.
To assess the impact of mycotoxin contaminations on drugs, Lootens et al. report that the use of a physiologically-based pharmacokinetic (PBPK) model can be an efficient in vitro tool.
Reference: Lootens, O.; Vermeulen, A.; Croubels, S.; De Saeger, S.; Van Bocxlaer, J.; De Boevre, M. Possible Mechanisms of the Interplay between Drugs and Mycotoxins—Is There a Possible Impact? Toxins 2022, 14, 873. https://doi.org/10.3390/toxins14120873
