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Exploration of cytochrome P450-related interactions between aflatoxin B1 and tiamulin in broiler chickens

Pan Sun (UGent) , Orphélie Lootens (UGent) , Tadele Kabeta Yadessa (UGent) , Diethard Reckelbus (UGent) , Natalia Furman, Xingyuan Cao, Suxia Zhang, Gunther Antonissen (UGent) , Siska Croubels (UGent) , Marthe De Boevre (UGent) , et al.
(2024) TOXINS. 16(3).
Author
Organization
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 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 (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
Toxicology, Mycotoxins, broiler chicken, antimicrobial drugs, CYP450 enzymes, tiamulin, aflatoxin B1, mycotoxin-drug interaction, pharmacokinetics, DRUG-METABOLIZING-ENZYMES, IN-VITRO, HEPATIC CYTOCHROME-P450, LIVER-MICROSOMES, ANTIBIOTIC TIAMULIN, ENZYMATIC-ACTIVITY, MESSENGER-RNA, B-1, EXPRESSION, ENROFLOXACIN

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MLA
Sun, Pan, et al. “Exploration of Cytochrome P450-Related Interactions between Aflatoxin B1 and Tiamulin in Broiler Chickens.” TOXINS, vol. 16, no. 3, MDPI, 2024, doi:10.3390/toxins16030160.
APA
Sun, P., Lootens, O., Yadessa, T. K., Reckelbus, D., Furman, N., Cao, X., … De Saeger, S. (2024). Exploration of cytochrome P450-related interactions between aflatoxin B1 and tiamulin in broiler chickens. TOXINS, 16(3). https://doi.org/10.3390/toxins16030160
Chicago author-date
Sun, Pan, Orphélie Lootens, Tadele Kabeta Yadessa, Diethard Reckelbus, Natalia Furman, Xingyuan Cao, Suxia Zhang, et al. 2024. “Exploration of Cytochrome P450-Related Interactions between Aflatoxin B1 and Tiamulin in Broiler Chickens.” TOXINS 16 (3). https://doi.org/10.3390/toxins16030160.
Chicago author-date (all authors)
Sun, Pan, Orphélie Lootens, Tadele Kabeta Yadessa, Diethard Reckelbus, Natalia Furman, Xingyuan Cao, Suxia Zhang, Gunther Antonissen, Siska Croubels, Marthe De Boevre, and Sarah De Saeger. 2024. “Exploration of Cytochrome P450-Related Interactions between Aflatoxin B1 and Tiamulin in Broiler Chickens.” TOXINS 16 (3). doi:10.3390/toxins16030160.
Vancouver
1.
Sun P, Lootens O, Yadessa TK, Reckelbus D, Furman N, Cao X, et al. Exploration of cytochrome P450-related interactions between aflatoxin B1 and tiamulin in broiler chickens. TOXINS. 2024;16(3).
IEEE
[1]
P. Sun et al., “Exploration of cytochrome P450-related interactions between aflatoxin B1 and tiamulin in broiler chickens,” TOXINS, vol. 16, no. 3, 2024.
@article{01HSXTCJSGWZBE8NXYGJR95SRP,
  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 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 (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.}},
  articleno    = {{160}},
  author       = {{Sun, Pan and Lootens, Orphélie and Yadessa, Tadele Kabeta and Reckelbus, Diethard and Furman, Natalia and Cao, Xingyuan and Zhang, Suxia and Antonissen, Gunther and Croubels, Siska and De Boevre, Marthe and De Saeger, Sarah}},
  issn         = {{2072-6651}},
  journal      = {{TOXINS}},
  keywords     = {{Toxicology,Mycotoxins,broiler chicken,antimicrobial drugs,CYP450 enzymes,tiamulin,aflatoxin B1,mycotoxin-drug interaction,pharmacokinetics,DRUG-METABOLIZING-ENZYMES,IN-VITRO,HEPATIC CYTOCHROME-P450,LIVER-MICROSOMES,ANTIBIOTIC TIAMULIN,ENZYMATIC-ACTIVITY,MESSENGER-RNA,B-1,EXPRESSION,ENROFLOXACIN}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{17}},
  publisher    = {{MDPI}},
  title        = {{Exploration of cytochrome P450-related interactions between aflatoxin B1 and tiamulin in broiler chickens}},
  url          = {{http://doi.org/10.3390/toxins16030160}},
  volume       = {{16}},
  year         = {{2024}},
}
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