Exploration of Cytochrome P450-Related Interactions between Aflatoxin B1 and Tiamulin in Broiler Chickens

Pan Sun; Orphélie Lootens; Tadele Kabeta; Diethard Reckelbus; Natalia Furman; Xingyuan Cao; Suxia Zhang; Gunther Antonissen; Siska Croubels; Marthe De Boevre; Sarah De Saeger

doi:10.3390/toxins16030160

Exploration of Cytochrome P450-Related Interactions between Aflatoxin B1 and Tiamulin in Broiler Chickens

Toxins (Basel). 2024 Mar 20;16(3):160. doi: 10.3390/toxins16030160.

Authors

Pan Sun^{1

2

3}, Orphélie Lootens^{1

4}, Tadele Kabeta^{2

5}, Diethard Reckelbus², Natalia Furman^{2

6}, Xingyuan Cao³, Suxia Zhang³, Gunther Antonissen⁶, Siska Croubels², Marthe De Boevre¹, Sarah De Saeger¹

Affiliations

¹ Department of Bioanalysis, Centre of Excellence in Mycotoxicology and Public Health, Faculty of Pharmaceutical Sciences, Ghent University, B-9000 Ghent, Belgium.
² Laboratory of Pharmacology and Toxicology, Department of Pathobiology, Pharmacology and Zoological Medicine, Faculty of Veterinary Medicine, Ghent University, B-9820 Merelbeke, Belgium.
³ Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
⁴ Laboratory of Medical Biochemistry and Clinical Analysis, Department of Bioanalysis, Ghent University, B-9000 Ghent, Belgium.
⁵ School of Veterinary Medicine, College of Agriculture and Veterinary Medicine, Jimma University, Jimma P.O. Box 307, Oromia, Ethiopia.
⁶ Chair Poultry Health Sciences, Department of Pathobiology, Pharmacology and Zoological Medicine, Faculty of Veterinary Medicine, Ghent University, B-9820 Merelbeke, Belgium.

Abstract

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 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_last) of TIA by 167% (p < 0.01). Additionally, the oral AFB1 pharmacokinetics revealed that TIA increased the AUC_last 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.

Keywords: CYP450 enzymes; aflatoxin B1; broiler chicken; mycotoxin-drug interaction; pharmacokinetics; tiamulin.

MeSH terms

Aflatoxin B1*
Animals
Anti-Bacterial Agents
Chickens*
Cytochrome P-450 Enzyme System
Diterpenes
Tandem Mass Spectrometry

Substances

Aflatoxin B1
tiamulin
Cytochrome P-450 Enzyme System
Anti-Bacterial Agents
Diterpenes

Grants and funding

This work was financially supported by the China Scholarship Council (202006350133).