Exploration of Cytochrome P450-Related Interactions between Aflatoxin B1 and Tiamulin in Broiler Chickens
2024
Pan Sun | Orphélie Lootens | Tadele Kabeta | Diethard Reckelbus | Natalia Furman | Xingyuan Cao | Suxia Zhang | Gunther Antonissen | Siska Croubels | Marthe De Boevre | Sarah De Saeger
Poultry may face simultaneous exposure to aflatoxin B1 (AFB1) and tiamulin (TIA), given mycotoxin contamination and antibiotic use. As both mycotoxins and antibiotics can affect cytochrome P450 enzymes (CYP450), our study aimed to explore their interaction. We developed UHPLC-MS/MS methods for the first-time determination of the interaction between TIA and AFB1 in vitro and in vivo in broiler chickens. The inhibition assay showed the half maximal inhibitory concentration (IC50) values of AFB1 and TIA in chicken liver microsomes are more than 7.6 &mu:M, indicating an extremely weak inhibitory effect on hepatic enzymes. Nevertheless, the oral TIA pharmacokinetic results indicated that AFB1 significantly increased the area under the plasma concentration-time curve (AUClast) of TIA by 167% (p <: 0.01). Additionally, the oral AFB1 pharmacokinetics revealed that TIA increased the AUClast and mean residence time (MRT) of AFB1 by 194% (p <: 0.01) and 136%, respectively. These results suggested that the observed inhibition may be influenced by other factors, such as transport. Therefore, it is meaningful to further explore transport and other enzymes, involved in the interaction between AFB1 and TIA. Furthermore, additional clinical studies are necessary to thoroughly assess the safety of co-exposure with mycotoxins and antibiotics.
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