Possible Mechanisms of the Interplay between Drugs and Mycotoxins—Is There a Possible Impact?

Abstract

Mycotoxin contamination is a global food safety issue leading to major public health concerns. Repeated exposure to multiple mycotoxins not only has repercussions on human health but could theoretically also lead to interactions with other xenobiotic substances—such as drugs—in the body by altering their pharmacokinetics and/or pharmacodynamics. The combined effects of chronic drug use and mycotoxin exposure need to be well understood in order to draw valid conclusions and, in due course, to develop guidelines. The aim of this review is to focus on food contaminants, more precisely on mycotoxins, and drugs. First, a description of relevant mycotoxins and their effects on human health and metabolism is presented. The potential for interactions of mycotoxins with drugs using in vitro and in vivo animal experiments is summarized. Predictive software tools for unraveling mycotoxin–drug interactions are proposed and future perspectives on this emerging topic are highlighted with a view to evaluate associated risks and to focus on precision medicine. In vitro and in vivo animal studies have shown that mycotoxins affect CYP450 enzyme activity. An impact from drugs on mycotoxins mediated via CYP450-enzymes is plausible; however, an impact of mycotoxins on drugs is less likely considering the much smaller dose exposure to mycotoxins. Drugs that are CYP450 perpetrators and/or substrates potentially influence the metabolism of mycotoxins, metabolized via these CYP450 enzymes. To date, very little research has been conducted on this matter. The only statistically sound reports describe mycotoxins as victims and drugs as perpetrators in interactions; however, more analysis on mycotoxin–drug interactions needs to be performed.

Using Microfluidic Hepatic Spheroid Cultures to Assess Liver Toxicity of T-2 Mycotoxin

“…As shown in Figure 3 , the expression of CYP1A1 ( Figure 3 A), CYP1A2 ( Figure 3 B), CYP2E1 ( Figure 3 C), CYP3A4 ( Figure 3 D), UGT1A1 ( Figure 3 E), MDR1 ( Figure 3 F), and MDR2 ( Figure 3 G) was induced by T-2, confirming that this mycotoxin is metabolized and excreted by HepG2 cells. The choice of enzymes was guided by prior reports of the liver metabolism of T-2 and other trichothecenes [ 48 , 49 , 50 ].…”

“…13, x FOR PEER REVIEW 11 of 18mycotoxin is metabolized and excreted by HepG2 cells. The choice of enzymes was guided by prior reports of the liver metabolism of T-2 and other trichothecenes[48][49][50].…”

Using In Silico Approach for Metabolomic and Toxicity Prediction of Alternariol

“…Cytochrome P450 (CYP450) are a family of enzymes with a key role in the metabolism of drugs and other xenobiotics, including mycotoxins [ 41 , 42 ]. Cyp450 enzymes can convert drugs/xenobiotics into less toxic compounds in order to prevent their toxicity or, on the contrary, generate reactive products (metabolites) that can cause toxicity [ 43 ].…”

Identification of Biotransformation Products of T-2 Toxin in HepG2 Cells Using LC-Q-TOF MS

“…According to Lootens et al, during the hydroxylation of the T-2 toxin in the liver, the CYP450s play an important role in the process of T-2 biotransformation, and the CYPs involved differ among different species of animals. The main CYP enzymes involved in the metabolism of T-2 are CYP3A22, CYP3A29 and CYP3A46 in pigs [27]; CYP1A4, CYP1A5, CYP2C18 and CYP3A37 in chickens [28]; and CYP1A1, CYP1A2, CYP2A1 and CYP2B4 in rabbits [29]. On the other hand, Lin et al reported that the contributions of the CYP450 enzyme family to T-2 metabolism in vitro followed the descending order of CYP3A4, CYP2E1, CYP1A2, CYP2B6 or CYP2D6 or CYP2C19 [30].…”