Introduction
Mycotoxins reach the animals’ bodies through the ingestion of contaminated feed. This feed can be contaminated at any level of the food chain, from harvesting, to processing, transportation or storage (Liu et al., 2022). Once these substances have been ingested, they are absorbed in the gastrointestinal tract, then distributed, metabolized and finally excreted.
During the metabolization processes that mycotoxins undergo inside the body, their biotransformation occurs. Is in the liver where these processes mainly occur, although the gastrointestinal tract also has an important metabolic function in animals (Tran et al., 2020). Biotransformation reactions are divided into two phases. The first phase includes oxidation, hydrolysis and reduction reactions; and the second, conjugation reaction (Lootens et al., 2022).
These reactions, sometimes, give rise to non-toxic or low-toxicity compounds, but metabolites that are more toxic than the initial mycotoxin can also be generated. In most of the biotransformation reactions of the first phase, cytochrome P450 (CYP450) is involved, it is a set of enzymes that plays a crucial role in the oxidative and reductive metabolism of many endogenous and exogenous chemical compounds (Tran et al., 2020).
Image 1. Tridimensional structure of cytochrome P450.
The function of this multi-enzyme complex in to transform substrates into more polar and water-soluble molecules, which make them easier to excrete. However, it sometimes can participate in the activation of toxic phenomena (Rodríguez et al.,2014). The expression of CYP450 is influenced by various factors, including health status and genetics. It is known that the expression of this group of enzymes varies depending on the animal species (Lootens et al., 2022).
Interaction between mycotoxins and drugs
Is the interaction of mycotoxins with CYP450, which makes that the presence of these substances in feed can affect to pharmacokinetics and pharmacodynamics of the xenobiotic metabolism processes. This is because this enzyme group is involved in approximately 80% of the metabolization process of drugs. Therefore, in the same way, the administration of these treatments can alter the metabolic pathways that biotransform mycotoxins (Lootens et al., 2022).
The interaction between mycotoxins and drugs can lead to different outcomes. It can lead to an increase in the effect of the administered drugs, as well as a reduced efficacy of the same. Meanwhile, the toxic effect of mycotoxins can be increased, or, in contrast, reduced (Lootens et al., 2022).
Some of the mycotoxins studied in this context have been aflatoxin B1 (AFB1), mycotoxin T-2, zearalenone (ZEN) and, an emerging mycotoxin, enniatin B1 (ENN B1), since this enzymatic group is involved in their metabolization pathways (Lootens et al., 2022). All of them, together with a large part of the drugs, can act as substrates, inducers and inhibitors of this complex. In addition, ZEN can act on a specific receptor of the enzyme.
Image 2: Diagram of mycotoxin and drug action on CYP450 (based on Lootens et al., 2022).
In this way, there is a possibility that administration of drugs to animals may not be effective due to the presence of mycotoxins in the feed, and this may also lead to cases of overdose, owing to a lack of metabolism of the same. On the other hand, the toxicity of some mycotoxins may be increased, either by the lack of inactivation, or, by an increase in the synthesis of more toxic metabolites.
Drugs can act as inducers or inhibitors. It is considered more likely that the reactions affecting mycotoxins will be altered by the administration of drugs than vice versa, taking into account the dose of exposure to both types of substances. In the case of AFB1, CYP450 participates in its bioactivation, generating aflatoxin-exo-8,9-epoxide and aflatoxin-endo-8,9-epoxide (AFBO), metabolites that are more toxic that the initial mycotoxin. For this reason, the administration of inducing drugs in those animals exposed to feed contaminated by AFB1, can lead to increase in its toxicity (Lootens et al., 2022).
Conclusions
Thus, it has been demonstrated that there is an interaction between the metabolism of mycotoxins and drugs. Until now, this subject has been barely studied, but is of particular interest because of its possible consequences on both animal health and public health. The problem of contamination by mycotoxins must be tackled effectively and decisively, since these substances, in addition to being capable of causing health problems in animals, can alter the effect of other essential compounds.
