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Investigating the combined toxicity of aflatoxin B1 and fumonisin B1 on HepG2 using respirometry and transcriptomic analyses

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Abstract
Aflatoxin B1 (AFB1) and fumonisin B1 (FB1) are widely (co-)detected in food and known for their hepatotoxicity in humans. Still, their combined toxicity needs to be investigated, especially the impact on mitochondria. In our previous work, we examined the effect of short-term exposure to different doses of AFB1, FB1, and their binary mixture (MIX) on the bioenergetic status of the HepG2 cells, a well-recognized in vitro model system to study liver cell function (Chen et al., 2022). The current work further investigated the (combined) effect of AFB1 and FB1 on the mitochondrial and glycolytic activity of the HepG2 cells using seahorse respirometry analysis and RNA transcriptome sequencing. The results showed that the co-exposure, especially at high doses, is more toxic due to a more inhibition of all parameters of mitochondrial respiration. However, FB1 contributes more to the MIX effects than AFB1. RNA transcriptome sequencing showed that the p53 signaling pathway, a major orchestrator of mitochondrial apoptosis, was differentially expressed. Moreover, the co-exposure has significantly downregulated Cx I, Cx II, Cx III, and Cx IV genes, representing the onset of the suppressed mitochondrial respiration in HepG2 cells. Acknowledgments This work was conducted within the Horizon 2020 IMPTOX project under the grant agreement No 965173. The authors thank China Scholarship Council (CSC) for providing X.C. with a Ph.D. scholarship (File No. 201806170042) to study at Ghent University, Belgium. M.F.A is supported by the Ghent University Special Research Fund (BOF) postdoc mandate with grant number BOF20/PDO/032. References Chen, X., Abdallah, M.F., Grootaert, C., Rajkovic, A., 2022. Bioenergetic Status of the Intestinal and Hepatic Cells after Short Term Exposure to Fumonisin B1 and Aflatoxin B1. International Journal of Molecular Sciences 23, 6945. https://doi.org/10.3390/ijms23136945
Keywords
aflatoxin B1, fumonisin B1, bioenergetics, seahorse analysis, combined toxicity, p53, apoptosis, transcriptomics

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Citation

Please use this url to cite or link to this publication:

MLA
Chen, Xiangrong, et al. “Investigating the Combined Toxicity of Aflatoxin B1 and Fumonisin B1 on HepG2 Using Respirometry and Transcriptomic Analyses.” Mycotoxin Workshop, 44th, Abstracts, Society for Mycotoxin Research, 2023, pp. 104–104.
APA
Chen, X., Abdallah, M. F., Grootaert, C., & Rajkovic, A. (2023). Investigating the combined toxicity of aflatoxin B1 and fumonisin B1 on HepG2 using respirometry and transcriptomic analyses. Mycotoxin Workshop, 44th, Abstracts, 104–104. Society for Mycotoxin Research.
Chicago author-date
Chen, Xiangrong, Mohamed Fathi Abdallah, Charlotte Grootaert, and Andreja Rajkovic. 2023. “Investigating the Combined Toxicity of Aflatoxin B1 and Fumonisin B1 on HepG2 Using Respirometry and Transcriptomic Analyses.” In Mycotoxin Workshop, 44th, Abstracts, 104–104. Society for Mycotoxin Research.
Chicago author-date (all authors)
Chen, Xiangrong, Mohamed Fathi Abdallah, Charlotte Grootaert, and Andreja Rajkovic. 2023. “Investigating the Combined Toxicity of Aflatoxin B1 and Fumonisin B1 on HepG2 Using Respirometry and Transcriptomic Analyses.” In Mycotoxin Workshop, 44th, Abstracts, 104–104. Society for Mycotoxin Research.
Vancouver
1.
Chen X, Abdallah MF, Grootaert C, Rajkovic A. Investigating the combined toxicity of aflatoxin B1 and fumonisin B1 on HepG2 using respirometry and transcriptomic analyses. In: Mycotoxin Workshop, 44th, Abstracts. Society for Mycotoxin Research; 2023. p. 104–104.
IEEE
[1]
X. Chen, M. F. Abdallah, C. Grootaert, and A. Rajkovic, “Investigating the combined toxicity of aflatoxin B1 and fumonisin B1 on HepG2 using respirometry and transcriptomic analyses,” in Mycotoxin Workshop, 44th, Abstracts, Celle (Hannover), Germany, 2023, pp. 104–104.
@inproceedings{01H2FFSG7Q2X9QJH0R8GAAXP30,
  abstract     = {{Aflatoxin B1 (AFB1) and fumonisin B1 (FB1) are widely (co-)detected in food and known for their hepatotoxicity in humans. Still, their combined toxicity needs to be investigated, especially the impact on mitochondria. In our previous work, we examined the effect of short-term exposure to different doses of AFB1, FB1, and their binary mixture (MIX) on the bioenergetic status of the HepG2 cells, a well-recognized in vitro model system to study liver cell function (Chen et al., 2022). The current work further investigated the (combined) effect of AFB1 and FB1 on the mitochondrial and glycolytic activity of the HepG2 cells using seahorse respirometry analysis and RNA transcriptome sequencing. The results showed that the co-exposure, especially at high doses, is more toxic due to a more inhibition of all parameters of mitochondrial respiration. However, FB1 contributes more to the MIX effects than AFB1. RNA transcriptome sequencing showed that the p53 signaling pathway, a major orchestrator of mitochondrial apoptosis, was differentially expressed. Moreover, the co-exposure has significantly downregulated Cx I, Cx II, Cx III, and Cx IV genes, representing the onset of the suppressed mitochondrial respiration in HepG2 cells.

Acknowledgments
This work was conducted within the Horizon 2020 IMPTOX project under the grant agreement No 965173. The authors thank China Scholarship Council (CSC) for providing X.C. with a Ph.D. scholarship (File No. 201806170042) to study at Ghent University, Belgium. M.F.A is supported by the Ghent University Special Research Fund (BOF) postdoc mandate with grant number BOF20/PDO/032.

References
Chen, X., Abdallah, M.F., Grootaert, C., Rajkovic, A., 2022. Bioenergetic Status of the Intestinal and Hepatic Cells after Short Term Exposure to Fumonisin B1 and Aflatoxin B1. International Journal of Molecular Sciences 23, 6945. https://doi.org/10.3390/ijms23136945}},
  articleno    = {{P35}},
  author       = {{Chen, Xiangrong and Abdallah, Mohamed Fathi and Grootaert, Charlotte and Rajkovic, Andreja}},
  booktitle    = {{Mycotoxin Workshop, 44th, Abstracts}},
  keywords     = {{aflatoxin B1,fumonisin B1,bioenergetics,seahorse analysis,combined toxicity,p53,apoptosis,transcriptomics}},
  language     = {{eng}},
  location     = {{Celle (Hannover), Germany}},
  pages        = {{P35:104--P35:104}},
  publisher    = {{Society for Mycotoxin Research}},
  title        = {{Investigating the combined toxicity of aflatoxin B1 and fumonisin B1 on HepG2 using respirometry and transcriptomic analyses}},
  url          = {{https://www.mycotoxin.de/previous-workshops}},
  year         = {{2023}},
}