Ochratoxin A and Epigenetics

  • Alessandra MezzelaniEmail author
Reference work entry


Ochratoxin A is a thermoresistant mycotoxin produced by ubiquitous molds of Aspergillus and Penicillium genera. It contaminates foodstuffs and feedstuffs worldwide and therefore is of human and animal concern.

Ochratoxin A induces oxidative stress, inflammation, and fibrosis, and is nephrotoxic, hepatotoxic, and neurotoxicin particularly in male subjects. Toxicity is mainly exerted through epigenetic mechanisms.

Nephrotoxicity is probably due to ochratoxin A-induced suppression of the collagen regulator mir-29b that results in an increase of translated collagen, fibrotic alteration, and nephropathy. Alternatively, ochratoxin A induces mir-132 upregulation that occurs in neurologic and psychiatric conditions as well as in oxidative stress. Undeniably, mir-132 acts in the reciprocal regulation of autism-related genes MeCP2 and PTEN decreasing the antioxidant Nrf2 that leads to the formation of high levels of reactive oxygen species. Reactive oxygen species, in turn, enhance the expression of mir-200c that impairs antioxidative mechanisms and synaptic plasticity through the reduction of HO-1 and NLGN4X. As for apoptosis, OTA exposure increases mir-122 that suppresses the anti-apoptotic genes Bcl-w and caspase-3 leading to cell death and hepatic damage.

Interestingly, both MECP2 and NLGN4X are involved in neurodevelopmental disorders, including autism, and are mapped on the X chromosome. As autism is a male predominant disorder, a possible contribution of ochratoxin A in its pathogenesis and in its strong male bias can be suggested.

Very few papers report about ochratoxin A-induced deacetylation:cells exposed to OTA underwent to a dramatic block of histone acetyltransferases leading to mitotic arrest and Nrf2 inhibition that, again, lead to reactive oxygen species formation.

Further studies are needed to obtain a complete picture of ochratoxin A-dependent epigenetic effects and to prevent or to counteract them.


Ochratoxin A Epigenetics microRNA Phenylalanine hydroxylase Nephrotoxic Neurotoxic Hepatotoxic Fibrosis Oxidative stress Neurodegenerative diseases Autism Nrf2 MECP2 NLGN4X Sex-dependent 

List of Abbreviations


Antioxidant responsive elements


Autism spectrum disorder (ASD)


β-Secretase-1 enzyme


Blood brain barrier


Brain-derived neurotropic factor


Balkan endemic nephropathy




CREB-binding protein


Central nervous system


DiGeorge syndrome critical region gene 8


Fragile X mental retardation protein


Histone acetyltransferase


Histone deacetylase


Heme oxygenase-1


Methyl-CpG-binding protein 2




Ochratoxin A


Adenoviral E1A-associated protein


Phenylalanine hydroxylase






Phosphatase and tensin homolog


Transforming-growth factor-beta


Nuclear factor erythroid 2-like 2


Reactive oxygen species




Zinc finger E-box binding homeobox 1


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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.National Research Council, Institute of Biomedical Technologies (CNR-ITB)Segrate (MI)Italy

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