New insights into the combined toxicity of aflatoxin B1 and fumonisin B1 in HepG2 cells using Seahorse respirometry analysis and RNA transcriptome sequencing

Chen, Xiangrong; Abdallah, Mohamed F.; Grootaert, Charlotte; Nieuwerburgh, Filip Van; Rajković, Andreja

doi:10.1016/j.envint.2023.107945

Cited by 9 publications

(26 citation statements)

References 60 publications

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“…Although the selected concentrations in the binary mixture of AFB1 and FB1 is different than the above mentioned studies, the ratio of both toxins is less than 20, and the synergistic interaction is still valid in hepatocytes. In addition, the same authors demonstrated that FB1 is contributing more than AFB1 to the mixture effects, based on RNA transcriptomic analysis [93], which is consistent with previous studies that showed that the binary mixture of AFB1 and FB1 would synergistically raise the hepatocarcinogenic properties. As shown in Figure 3, with AFB1 and FB1 having different mechanisms of action, there could be a potential of promoting each other via crossing pathways.…”

Section: Combined Toxicity Of Afb1 and Fb1 In Human Cellssupporting

confidence: 85%

“…In this interaction, they argued that AFB1 had a major input into the mixture's prooxidant activity, with cytochrome P450 and arachidonic acid being ROS contributors, but that FB1 was weak at invoking these pathways [92]. Chen et al have also reported that the mixture of AFB1 (25.6 µM) and FB1 (224 µM) significantly increased the p53 protein, and downregulated the mitochondrial complexes in HepG2 cells [93]. Although the selected concentrations in the binary mixture of AFB1 and FB1 is different than the above mentioned studies, the ratio of both toxins is less than 20, and the synergistic interaction is still valid in hepatocytes.…”

Section: Combined Toxicity Of Afb1 and Fb1 In Human Cellsmentioning

confidence: 99%

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Current Knowledge of Individual and Combined Toxicities of Aflatoxin B1 and Fumonisin B1 In Vitro

Chen,

F. Abdallah,

Chen

et al. 2023

Toxins

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Mycotoxins are considered the most threating natural contaminants in food. Among these mycotoxins, aflatoxin B1 (AFB1) and fumonisin B1 (FB1) are the most prominent fungal metabolites that represent high food safety risks, due to their widespread co-occurrence in several food commodities, and their profound toxic effects on humans. Considering the ethical and more humane animal research, the 3Rs (replacement, reduction, and refinement) principle has been promoted in the last few years. Therefore, this review aims to summarize the research studies conducted up to date on the toxicological effects that AFB1 and FB1 can induce on human health, through the examination of a selected number of in vitro studies. Although the impact of both toxins, as well as their combination, were investigated in different cell lines, the majority of the work was carried out in hepatic cell lines, especially HepG2, owing to the contaminants’ liver toxicity. In all the reviewed studies, AFB1 and FB1 could invoke, after short-term exposure, cell apoptosis, by inducing several pathways (oxidative stress, the mitochondrial pathway, ER stress, the Fas/FasL signaling pathway, and the TNF-α signal pathway). Among these pathways, mitochondria are the primary target of both toxins. The interaction of AFB1 and FB1, whether additive, synergistic, or antagonistic, depends to great extent on FB1/AFB1 ratio. However, it is generally manifested synergistically, via the induction of oxidative stress and mitochondria dysfunction, through the expression of the Bcl-2 family and p53 proteins. Therefore, AFB1 and FB1 mixture may enhance more in vitro toxic effects, and carry a higher significant risk factor, than the individual presence of each toxin.

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Section: Combined Toxicity Of Afb1 and Fb1 In Human Cellssupporting

confidence: 85%

Section: Combined Toxicity Of Afb1 and Fb1 In Human Cellsmentioning

confidence: 99%

Current Knowledge of Individual and Combined Toxicities of Aflatoxin B1 and Fumonisin B1 In Vitro

Chen,

F. Abdallah,

Chen

et al. 2023

Toxins

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“…Notably, even low doses of AFB1 exposure can lead to abnormal changes in mitochondrial structure, membrane potential, and expression of genes involved in electron transport chain complexes in the liver of mice [127]. Moreover, AFB1 exposure has been linked to the diminished mRNA expression of key regulators, such as nuclear respiratory factor 1 (Nrf1), mitochondrial transcription factor A (MTFA), PGC-1α, and peroxisome proliferator-activated receptor γ coactivator 1α (PPAR1α), important for mitochondrial biosynthesis [48,127,128]. Notably, MTFA is a direct regulator of mitochondrial DNA replication/transcription.…”

Section: Inhibition Of Mitochondrial Dysfunction and Apoptosismentioning

confidence: 99%

Lycopene as a Therapeutic Agent against Aflatoxin B1-Related Toxicity: Mechanistic Insights and Future Directions

Li,

Tang,

Peng

et al. 2024

Antioxidants

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Aflatoxin (AFT) contamination poses a significant global public health and safety concern, prompting widespread apprehension. Of the various AFTs, aflatoxin B1 (AFB1) stands out for its pronounced toxicity and its association with a spectrum of chronic ailments, including cardiovascular disease, neurodegenerative disorders, and cancer. Lycopene, a lipid-soluble natural carotenoid, has emerged as a potential mitigator of the deleterious effects induced by AFB1 exposure, spanning cardiac injury, hepatotoxicity, nephrotoxicity, intestinal damage, and reproductive impairment. This protective mechanism operates by reducing oxidative stress, inflammation, and lipid peroxidation, and activating the mitochondrial apoptotic pathway, facilitating the activation of mitochondrial biogenesis, the endogenous antioxidant system, and the nuclear factor erythroid 2-related factor 2 (Nrf2)/kelch-like ECH-associated protein 1 (KEAP1) and peroxisome proliferator-activated receptor-γ coactivator-1 (PGC-1) pathways, as well as regulating the activities of cytochrome P450 (CYP450) enzymes. This review provides an overview of the protective effects of lycopene against AFB1 exposure-induced toxicity and the underlying molecular mechanisms. Furthermore, it explores the safety profile and potential clinical applications of lycopene. The present review underscores lycopene’s potential as a promising detoxification agent against AFB1 exposure, with the intent to stimulate further research and practical utilization in this domain.

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“…Fumonisins (FUMs) are water-soluble mycotoxins released by Fusarium spp , which commonly exist in corn (Dopavogui et al 2023 ; Yang et al 2023 ). However, fumonisin B1 (FB1) is the most toxic one of the fumonisins and causes serious harm to both human and animal health (Chen et al 2023 ; Ezekiel et al 2022 ; Yu et al 2021 ). It triggers a diversity of damage in the body, including hepatointestinal injury, pulmonary edema, inflammatory response, and other forms of diseases (Chen et al 2023 ; Gao et al 2023 ).…”

Section: Introductionmentioning

confidence: 99%

“…However, fumonisin B1 (FB1) is the most toxic one of the fumonisins and causes serious harm to both human and animal health (Chen et al 2023 ; Ezekiel et al 2022 ; Yu et al 2021 ). It triggers a diversity of damage in the body, including hepatointestinal injury, pulmonary edema, inflammatory response, and other forms of diseases (Chen et al 2023 ; Gao et al 2023 ). More recently, it was reported that FB1 induced cell apoptosis and caused organ damage by activating oxidative stress (Cao et al 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Mild endoplasmic reticulum stress alleviates FB1-triggered intestinal pyroptosis via the Sec62-PERK pathway

Ma,

Li,

Yue

et al. 2024

Cell Biol Toxicol

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Fumonisin B1 (FB1), a water-soluble mycotoxin released by Fusarium moniliforme Sheld, is widely present in corn and its derivative products, and seriously endangers human life and health. Recent studies have reported that FB1 can lead to pyroptosis, however, the mechanisms by which FB1-induced pyroptosis remain indistinct. In the present study, we aim to investigate the mechanisms of pyroptosis in intestinal porcine epithelial cells (IPEC-J2) and the relationship between FB1-induced endoplasmic reticulum stress (ERS) and pyroptosis. Our experimental results showed that the pyroptosis protein indicators in IPEC-J2 were significantly increased after exposure to FB1. The ERS markers, including glucose-regulated Protein 78 (GRP78), PKR-like ER kinase protein (PERK), and preprotein translocation factor (Sec62) were also significantly increased. Using small interfering RNA silencing of PERK or Sec62, the results demonstrated that upregulation of Sec62 activates the PERK pathway, and activation of the PERK signaling pathway is upstream of FB1-induced pyroptosis. After using the ERS inhibitor 4-PBA reduced the FB1-triggered intestinal injury by the Sec62-PERK pathway. In conclusion, we found that FB1 induced pyroptosis by upregulating Sec62 to activate the PERK pathway, and mild ERS alleviates FB1-triggered damage. It all boils down to one fact, the study provides a new perspective for further, and improving the toxicological mechanism of FB1. Graphical Abstract

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New insights into the combined toxicity of aflatoxin B1 and fumonisin B1 in HepG2 cells using Seahorse respirometry analysis and RNA transcriptome sequencing

Cited by 9 publications

References 60 publications

Current Knowledge of Individual and Combined Toxicities of Aflatoxin B1 and Fumonisin B1 In Vitro

Current Knowledge of Individual and Combined Toxicities of Aflatoxin B1 and Fumonisin B1 In Vitro

Lycopene as a Therapeutic Agent against Aflatoxin B1-Related Toxicity: Mechanistic Insights and Future Directions

Mild endoplasmic reticulum stress alleviates FB1-triggered intestinal pyroptosis via the Sec62-PERK pathway

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