Zearalenone induced toxicity in SHSY-5Y cells: the role of oxidative stress evidenced by N-acetyl cysteine
Abstract
Zearalenone (ZEN) is a mycotoxin from Fusarium species commonly found in many food commodities and are known to cause reproductive disorders, genotoxic and immunosuppressive effects. Although many studies have demonstrated the cytotoxic effects of ZEN, the mechanisms by which ZEN mediates its cytotoxic effects appear to differ according to cell type and route of exposure. Meantime, the available information on the neurotoxic effects of ZEN is very much limited. In the present study we evaluated the role of oxidative stress in ZEN mediated neurotoxicity in SH-SY5Y cells and investigated the possible underlying mechanism. ZEN induced ROS formation and elevated levels of MDA, loss of mitochondrial membrane potential (MMP) and increase in DNA damage in a dose dependent manner as assessed by COMET assay and agarose gel electrophoresis. However, there was no DNA damage by plasmid breakage assay at 6, 12 and 24h time points. DAPI staining showed apoptotic nuclei at 12 and 24h. Further, ZEN treated SH-SY5Y cells showed a marked suppressive effect on the neuronal gene expression. Use of an antioxidant N-acetylcysteine (NAC) reversed the toxin-induced generation of ROS and also attenuated loss of MMP. Collectively, these results suggest that ROS is the main upstream signal leading to increased ZEN mediated neurotoxicity in SH-SY5Y cells.
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Exposure to mycotoxins such as ZEN may reduce the brain's capacity for adaptive synaptic remodeling, contributing to cognitive dysfunction.
“Exposure to mycotoxins such as ZEN is therefore thought to reduce the brain’s capacity for adaptive synaptic remodeling, ultimately contributing to cognitive dysfunction (Venkataramana et al., 2014).”
From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Venkataramana et al., 2014
ZEN significantly suppresses gene expression in nerve cells, an effect linked to induction of oxidative stress, which is considered a central upstream signal in its neurotoxic action.
“At the neuronal level, ZEN significantly suppresses gene expression in nerve cells, an effect closely linked to the induction of oxidative stress, which is considered a central upstream signal in its neurotoxic action.”
From Environmental endocrine disruptors at the synapse: mechanisms linking chemical exposure to cognitive and behavioral dysfunction (2026) · cites this paper as Venkataramana et al., 2014
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Seralini, G.-E., & Jungers, G. (2021) · Toxicology Reports · doi:10.1016/j.toxrep.2021.07.014 · Cited by 57 · see citing works
Barai, P., Raval, N., Acharya, S., & Acharya, N. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.09.011 · Cited by 21 · see citing works
Kiss, D., Ioja, E., Toth, I., Barany, Z., Jocsak, G., Bartha, T., Horvath, T., & Zsarnovszky, A. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19051440 · Cited by 18 · see citing works
Jocsak, G., Kiss, D. S., Alymbaeva, D., Diebald, A., Zsarnovszky, A., Heinzlmann, A., & Bartha, T. (2026) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2026.1821381 · Cited by 1 · see citing works
“Exposure to mycotoxins such as ZEN is therefore thought to reduce the brain’s capacity for adaptive synaptic remodeling, ultimately contributing to cognitive dysfunction (Venkataramana et al., 2014).”
- Authors
- Venkataramana, M., Chandra Nayaka, S., Anand, T., Rajesh, R., Aiyaz, M., Divakara, S. T., Murali, H. S., Prakash, H. S., & Lakshmana Rao, P. V.
- Affiliations
- Defence Research and Development Organisation (IN)
- Defence Food Research Laboratory (IN)
- University of Mysore (IN)
- Venue
- Food and Chemical Toxicology
- Publisher
- Elsevier BV
- Published
- 2014-03
- Volume
- 65
- Pages
- 335-342
- ISSN
- 0278-6915 (ISSN-L)
- OpenAlex
- W2077491931
- Cited by
- 118
- References
- 0
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 7 · 2023: 4 · 2022: 8 · 2021: 16 · 2020: 8 · 2019: 14 · 2018: 19 · 2017: 6 · 2016: 11 · 2015: 11 · 2014: 4
- FWCI
- 12.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Food and Chemical Toxicology (publishedVersion)
- PubMed (publishedVersion)
- MyPrints@UOM (Mysore University Library) (submittedVersion)
- Funders
- University Grants Commission
- Ministry of Education, India
- University of Mysore
- Topics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Mycotoxins in Agriculture and Food
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Bioactive Compounds and Antitumor Agents
- Keywords
- zearalenone, mycotoxin neurotoxicity, oxidative stress, reactive oxygen species, N-acetylcysteine, SH-SY5Y cells, mitochondrial membrane potential, lipid peroxidation, DNA damage, apoptosis, neuronal gene expression, antioxidant defense
- MeSH terms
- Acetylcysteine, Base Sequence, Humans, Zearalenone, Reactive Oxygen Species, DNA Primers, Oxidative Stress, Cell Line, Tumor, Membrane Potential, Mitochondrial, Real-Time Polymerase Chain Reaction
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