Department of Bioanalysis, Centre of Excellence in Mycotoxicology and Public Health, Faculty of Pharmaceutical Sciences, Ghent University, B-9000 Ghent, Belgium.
Laboratory of Pharmacology and Toxicology, Department of Pathobiology, Pharmacology and Zoological Medicine, Faculty of Veterinary Medicine, Ghent University, B-9820 Merelbeke, Belgium.
Toxins (Basel). 2024 Mar 20;16(3):160. doi: 10.3390/toxins16030160.
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 (IC) values of AFB1 and TIA in chicken liver microsomes are more than 7.6 μM, 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 (AUC) of TIA by 167% ( < 0.01). Additionally, the oral AFB1 pharmacokinetics revealed that TIA increased the AUC and mean residence time (MRT) of AFB1 by 194% ( < 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.
家禽可能同时面临黄曲霉毒素 B1（AFB1）和泰妙菌素（TIA）的暴露，这是由于霉菌毒素污染和抗生素的使用。鉴于霉菌毒素和抗生素都能影响细胞色素 P450 酶（CYP450），我们的研究旨在探索它们之间的相互作用。我们首次开发了 UHPLC-MS/MS 方法，用于测定黄曲霉毒素 B1 和泰妙菌素在体外和体内肉鸡中的相互作用。抑制试验表明，AFB1 和 TIA 在鸡肝微粒体中的半数最大抑制浓度（IC）值大于 7.6 μM，表明对肝酶的抑制作用极弱。然而，口服 TIA 的药代动力学结果表明，AFB1 使 TIA 的血浆浓度-时间曲线下面积（AUC）增加了 167%（<0.01）。此外，口服 AFB1 的药代动力学研究表明，TIA 使 AFB1 的 AUC 和平均驻留时间（MRT）分别增加了 194%（<0.01）和 136%。这些结果表明，观察到的抑制可能受到其他因素的影响，如转运。因此，进一步探索转运和其他参与 AFB1 和 TIA 相互作用的酶具有重要意义。此外，需要进行更多的临床研究来全面评估霉菌毒素和抗生素同时暴露的安全性。
