Abstract
Deoxynivalenol (DON) is a type B trichothecenes that is widely contaminating human and animal foods, leading to several toxicological implications if ingested. Induction of oxidative stress and production of lipid peroxides were suggested to be the reasons for DON-induced cytotoxicity. However, detailed and comprehensive profiling of DON-related lipid hydroperoxides was not identified. Furthermore, the mechanisms behind DON-induced cytotoxicity and oxidative stress have received less attention. Zinc (Zn) is an essential element that has antioxidant activities; however, the protective effects of Zn against DON-induced adverse effects were not examined. Therefore, this study was undertaken to investigate DON-induced cytotoxicity and oxidative damage to human HepG2 cell lines. Furthermore, a quantitative estimation for the formed lipid hydroperoxides was conducted using LC-MS/MS. In addition, DON-induced transcriptomic changes on the inflammatory markers and antioxidant enzymes were quantitatively examined using qPCR. The protective effects of Zn against DON-induced cytotoxicity and oxidative stress, the formation of lipid hydroperoxides (LPOOH), and antioxidant status in HepG2 cells were investigated. Finally, the effects of DON and Zn on the Nrf2-Keap1 pathway were further explored. The achieved results indicated that DON caused significant cytotoxicity in HepG2 cells accompanied by significant oxidative damage and induction of the inflammatory markers. Identification of DON-related LPOOH revealed the formation of 22 LPOOH species including 14 phosphatidylcholine hydroperoxides, 5 triacylglycerol hydroperoxides, and 3 cholesteryl ester hydroperoxides. DON caused significant downregulation of Nrf2-regulated antioxidant enzymes. Zn administration led to significant protection of HepG2 cells against DON-induced adverse effects, probably via activation of the Nrf2-Keap1 pathway.
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Change history
20 August 2021
A Correction to this paper has been published: https://doi.org/10.1007/s12550-021-00440-0
23 April 2020
A Correction to this paper has been published: https://doi.org/10.1007/s12550-020-00394-9
Abbreviations
- DON:
-
Deoxynivalenol
- Zn:
-
Zinc
- HepG2:
-
Human liver hepatoma cell lines
- PCOOH:
-
Phosphatidylcholine hydroperoxides
- TGOOH:
-
Triacylglycerol hydroperoxides
- CEOOH:
-
Cholesteryl ester hydroperoxides
- DMEM:
-
Dulbecco’s modified Eagle’s medium
- DCF-DA:
-
2′,7′-Dichlorofluorescein diacetate
- qPCR:
-
Quantitative real-time PCR
- GST:
-
Glutathione-S-transferases
- NQO1:
-
NAD(P)H dehydrogenase [quinone] 1
- HO 1:
-
Heme oxygenase 1
- SOD:
-
Superoxide dismutase
- CAT:
-
Catalase
- Nrf2:
-
Erythroid 2–related factor 2
- Keap1:
-
Kelch-like ECH-associated protein-1
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This study was supported by the Ministry of Education, Culture, Sports, Science and Technology, Japan.
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Darwish, W.S., Chen, Z., Li, Y. et al. RETRACTED ARTICLE: Deoxynivalenol-induced alterations in the redox status of HepG2 cells: identification of lipid hydroperoxides, the role of Nrf2-Keap1 signaling, and protective effects of zinc. Mycotoxin Res 36, 287–299 (2020). https://doi.org/10.1007/s12550-020-00392-x
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DOI: https://doi.org/10.1007/s12550-020-00392-x