New insights into the combined toxicity of aflatoxin B1 and fumonisin B1 in HepG2 cells using Seahorse respirometry analysis and RNA transcriptome sequencing. - 2023
New insights into the combined toxicity of aflatoxin B1 and fumonisin B1 in HepG2 cells using Seahorse respirometry analysis and RNA transcriptome sequencing.
[en] 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 HepG2 cells, a well-recognized in vitro model system for studying liver cell function. In the current work, we further investigated the (combined) effect of AFB1 and FB1 on the mitochondrial and glycolytic activity of 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 significantly downregulated the genes encoding for Complexes I, II, III, and IV, representing the onset of the suppressed mitochondrial respiration in HepG2 cells.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Chen, Xiangrong; Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium. Electronic address: xiangrong.chen@ugent.be
Abdallah, Mohamed Fathi ; UGent - Universiteit Gent [BE] > Faculty of Bioscience Engineering > Department of Food Technology, Safety and Health ; Assiut University > Faculty of Veterinary Medicine > Department of Forensic Medicine and Toxicology
Grootaert, Charlotte; Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium
Van Nieuwerburgh, Filip; Laboratory of Pharmaceutical Biotechnology, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium
Rajkovic, Andreja; Department of Food Technology, Safety and Health, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium. Electronic address: andreja.rajkovic@ugent.be
Language :
English
Title :
New insights into the combined toxicity of aflatoxin B1 and fumonisin B1 in HepG2 cells using Seahorse respirometry analysis and RNA transcriptome sequencing.
This work was conducted within the Horizon 2020 IMPTOX project (https://www.imptox.eu), funded by the European Union’s Horizon 2020 research and innovation program under the grant agreement No 965173, Research Foundation Flanders research grant 1506419N given to AR, Ghent University Special Research Fund grant given BOF20/BAS/120 to AR for the purchase of Seahorse XF analyzer.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. The authors thank Ghent University and their respective Faculties and Departments for teamwork, support, and general infrastructure.
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