Ochratoxin A induces global DNA hypomethylation and oxidative stress in neuronal cells in vitro

Recently, it was reported that ochratoxin A (OTA) mycotoxin, produced by a number of Aspergillus and Penicillium fungal species, may cause neuropsychological impairment or mental and emotional disorders but the mechanism of neurotoxicity remains unknown. Adverse effects of OTA in human (SHSY5Y) and...

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Bibliographic Details
Published in:	Mycotoxin research Vol. 36; no. 1; pp. 73 - 81
Main Authors:	Babayan, Nelly, Tadevosyan, Gohar, Khondkaryan, Lusine, Grigoryan, Ruzanna, Sarkisyan, Natalya, Haroutiounian, Rouben, Stopper, Helga
Format:	Journal Article
Language:	English
Published:	Berlin/Heidelberg Springer Berlin Heidelberg 01-02-2020 Springer Nature B.V
Subjects:	Animals Biomedical and Life Sciences Biotechnology Cell Line Cell lines Chemistry/Food Science Chromosomes - drug effects CpG islands Cytotoxicity Deoxyribonucleic acid DNA DNA Methylation - drug effects Fungi Genomic instability Genotoxicity Humans Life Sciences Medical Microbiology Medicine/Public Health Mice Microbiology Mycotoxins Mycotoxins - toxicity Neurons - drug effects Neurons - pathology Neurotoxicity Neurotoxicity Syndromes Ochratoxin A Ochratoxins - toxicity Original Article Oxidative stress Oxidative Stress - drug effects Purines Reactive oxygen species Reactive Oxygen Species - metabolism Stability Toxicity Epigenetics Oxidative stress Cytotoxicity Ochratoxin A In vitro Genotoxicity
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Summary:	Recently, it was reported that ochratoxin A (OTA) mycotoxin, produced by a number of Aspergillus and Penicillium fungal species, may cause neuropsychological impairment or mental and emotional disorders but the mechanism of neurotoxicity remains unknown. Adverse effects of OTA in human (SHSY5Y) and mouse (HT22) neuronal cell lines were studied in vitro. OTA was found to be non-cytotoxic in both cell lines at concentrations 2.5–30 μmol/l, which are above the levels reported for human and animal plasma. OTA led to slightly elevated chromosomal instability in HT22 cells at concentrations of 15–30 μmol/l after 48 h, while in SHSY5Y cells, no evidence for genotoxic effects was observed at concentrations of 2.5–30 μmol/l. OTA treatment at 10 μmol/l resulted in elevated levels of unmethylated cytosines in CpG dinucleotides (up to 1.4-fold), elevated levels of intracellular reactive oxygen species (up to 1.6-fold), and in elevated levels of oxidized DNA purines (up to 2.2-fold) in both cell lines. Detected global DNA hypomethylation and oxidative stress were found to be reversible in 96 h and 24–72 h, respectively. In general, the observed pattern of OTA-induced effects in both cell lines was similar, but HT22 cells exhibited higher sensitivity, as well as better repair capacity in response to OTA toxicity. In conclusion, the results suggest that oxidative stress and epigenetic changes are directly involved in OTA-induced neurotoxicity, while cytotoxicity and genotoxicity cannot be considered as primary cause of toxicity in neuronal cells in vitro.
ISSN:	0178-7888 1867-1632
DOI:	10.1007/s12550-019-00370-y