The metabolic responses of HepG2 cells to the exposure of mycotoxin deoxynivalenol

Liu, Y.; Ran, Ruoshi; Hu, Chaoyang; Cui, Bo; Xu, Yunze; Liu, H.; Quan, Sheng; Li, D.; Li, X.; Wu, Yongning; Zhang, Dingguo; Shi, Jiannong

doi:10.3920/wmj2015.1981

Cited by 9 publications

(7 citation statements)

References 39 publications

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“…Liu et al. (, see supplementary information) confirmed the DNA damaging effects of DON at a concentration of 3 μg/mL, and of the protecting effect of HT, using the same methodology as Zhang et al. ().…”

Section: Hazard Identification and Characterisationmentioning

confidence: 81%

“…DON‐dependent production of reactive oxygen species (ROS) has been reported in several cell culture studies as well as in vivo in the intestine (review Mishra et al., ). It should be noted that, DON‐induced ROS generation proved to be an early event (Liu et al., ) which might lead to genotoxicity (see Section 7.2.9). Modifications in antioxidant enzyme activities have been used as a biosensor for ROS formation during the oxidative assault in the cell system.…”

Section: Hazard Identification and Characterisationmentioning

confidence: 99%

See 1 more Smart Citation

Risks to human and animal health related to the presence of deoxynivalenol and its acetylated and modified forms in food and feed

Knutsen¹,

Alexander²,

Barregård³

et al. 2017

EFS2

192

187

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Deoxynivalenol (DON) is a mycotoxin primarily produced by Fusarium fungi, occurring predominantly in cereal grains. Following the request of the European Commission, the CONTAM Panel assessed the risk to animal and human health related to DON, 3-acetyl-DON (3-Ac-DON), 15-acetyl-DON (15-Ac-DON) and DON-3-glucoside in food and feed. A total of 27,537, 13,892, 7,270 and 2,266 analytical data for DON, 3-Ac-DON, 15-Ac-DON and DON-3-glucoside, respectively, in food, feed and unprocessed grains collected from 2007 to 2014 were used. For human exposure, grains and grain-based products were main sources, whereas in farm and companion animals, cereal grains, cereal by-products and forage maize contributed most. DON is rapidly absorbed, distributed, and excreted. Since 3-Ac-DON and 15-Ac-DON are largely deacetylated and DON-3-glucoside cleaved in the intestines the same toxic effects as DON can be expected. The TDI of 1 lg/kg bw per day, that was established for DON based on reduced body weight gain in mice, was therefore used as a group-TDI for the sum of DON, 3-Ac-DON, 15-Ac-DON and DON-3-glucoside. In order to assess acute human health risk, epidemiological data from mycotoxicoses were assessed and a group-ARfD of 8 lg/kg bw per eating occasion was calculated. Estimates of acute dietary exposures were below this dose and did not raise a health concern in humans. The estimated mean chronic dietary exposure was above the group-TDI in infants, toddlers and other children, and at high exposure also in adolescents and adults, indicating a potential health concern. Based on estimated mean dietary concentrations in ruminants, poultry, rabbits, dogs and cats, most farmed fish species and horses, adverse effects are not expected. At the high dietary concentrations, there is a potential risk for chronic adverse effects in pigs and fish and for acute adverse effects in cats and farmed mink.This is an open access article under the terms of the Creative Commons Attribution-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited and no modifications or adaptations are made.The EFSA Journal is a publication of the European Food Safety Authority, an agency of the European Union. Deoxynivalenol and its acetylated and modified forms in food and feed www.efsa.europa.eu/efsajournal 2 EFSA Journal 2017;15(9):4718 Deoxynivalenol and its acetylated and modified forms in food and feed www.efsa.europa.eu/efsajournal 3 EFSA Journal 2017;15(9):4718 Deoxynivalenol and its acetylated and modified forms in food and feed www.efsa.europa.eu/efsajournal 4 EFSA Journal 2017;15(9):471870% of ingested DON is excreted via urine, of which about 80% was in conjugated forms, mainly as DON-15-glucuronide that was about threefold more efficiently formed than DON-3-glucuronide. After a single oral exposure to DON, feed refusal appeared very quickly in mice. Previous risk assessments of DON conducted by the Scientific Committee on Food (SCF) in 1999 and by the Joint FAO/WHO Expert Committee on Food Additives...

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Section: Hazard Identification and Characterisationmentioning

confidence: 81%

Section: Hazard Identification and Characterisationmentioning

confidence: 99%

Risks to human and animal health related to the presence of deoxynivalenol and its acetylated and modified forms in food and feed

Knutsen¹,

Alexander²,

Barregård³

et al. 2017

EFS2

192

187

View full text Add to dashboard Cite

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“…The studies have shown that DON causes oxidative stress and causes both molecular and cellular modification in HepG2 cells (Zhang et al, 2009, Liu et al, 2016, Zhou et al, 2017.…”

Section: Nrf2 Antioxidant Responsementioning

confidence: 99%

Deoxynivalenol downregulates NRF2-induced cytoprotective response in human hepatocellular carcinoma (HepG2) cells

Ndlovu

Nagiah

Abdul

et al. 2021

Toxicon

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“…Ponchon and co-workers suggested that the effects of mycotoxins would impact hepatic cholesterol biosynthesis and subsequently vitamin D activation [ 16 ]. Mycotoxin-induced lipid/cholesterol metabolism dysregulation also entails energy imbalance and altered cell membrane integrity [ 17 , 18 ]. For instance, DON treatment changes the lipid profile of cells including decreasing levels of lysolipids, sphingolipids, sterols and free fatty acids (FA), as well as down-regulating bile acid metabolism [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

“…Mycotoxin-induced lipid/cholesterol metabolism dysregulation also entails energy imbalance and altered cell membrane integrity [ 17 , 18 ]. For instance, DON treatment changes the lipid profile of cells including decreasing levels of lysolipids, sphingolipids, sterols and free fatty acids (FA), as well as down-regulating bile acid metabolism [ 17 ]. However, the molecular network behind this is not fully understood.…”

Section: Introductionmentioning

confidence: 99%

Orphan Nuclear Receptor RORγ Modulates the Genome-Wide Binding of the Cholesterol Metabolic Genes during Mycotoxin-Induced Liver Injury

Zhang

et al. 2021

Nutrients

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Maintaining lipid homeostasis is crucial to liver function, the key organ that governs the whole-body energy metabolism. In contrast, lipid dysregulation has been implicated in mycotoxin-induced liver injury, by which the pathophysiological regulation and the molecular components involved remain elusive. Here we focused on the potential roles of orphan nuclear receptor (NR) RORγ in lipid programming, and aimed to explore its action on cholesterol regulation in the liver of mycotoxin-exposed piglets. We found that liver tissues were damaged in the mycotoxin-exposed piglets compared to the healthy controls, revealed by histological analysis, elevated seral ALT, AST and ALP levels, and increased caspase 3/7 activities. Consistent with the transcriptomic finding of down-regulated cholesterol metabolism, we demonstrated that both cholesterol contents and cholesterol biosynthesis/transformation gene expressions in the mycotoxin-exposed livers were reduced, including HMGCS1, FDPS, SQLE, EBP, FDFT1 and VLDLR. Furthermore, we reported that RORγ binds to the cholesterol metabolic genes in porcine hepatocytes using a genome-wide ChIP-seq analysis, whereas mycotoxin decreased the RORγ binding occupancies genome-wide, especially at the cholesterol metabolic pathway. In addition, we revealed the enrichment of co-factors p300 and SRC, the histone marks H3K27ac and H3K4me2, together with RNA Polymerase II (Pol-II) at the locus of HMGCS1 in hepatocytes, which were reduced by mycotoxin-exposure. Our results provide a deep insight into the cholesterol metabolism regulation during mycotoxin-induced liver injury, and propose NRs as therapeutic targets for anti-mycotoxin treatments.

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The metabolic responses of HepG2 cells to the exposure of mycotoxin deoxynivalenol

Cited by 9 publications

References 39 publications

Risks to human and animal health related to the presence of deoxynivalenol and its acetylated and modified forms in food and feed

Risks to human and animal health related to the presence of deoxynivalenol and its acetylated and modified forms in food and feed

Deoxynivalenol downregulates NRF2-induced cytoprotective response in human hepatocellular carcinoma (HepG2) cells

Orphan Nuclear Receptor RORγ Modulates the Genome-Wide Binding of the Cholesterol Metabolic Genes during Mycotoxin-Induced Liver Injury

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