Abstract
Embryonic midbrain micromass cultures were exposed for five days to ochratoxin A (OTA) at seven concentrations (ranging from 0.16 to 10 μg/mL). Cell viability was assessed in neutral red uptake test (NRU), and differentiation – by immunoenzymatic determination of structural proteins (βIII-tubulin, MAP2, GFAP) expression level as well as by computer image analysis. Dose dependent decrease in cell number and differentiation was observed. Concentration-response curves were analysed and the mean inhibition concentrations (μg/mL) for cytotoxicity (IC50) and differentiation (ID50) were calculated. There were no significant differences in the sensitivity of neurons in early and late stage of differentiation and astrocytes to the toxic activity of this compound. For all endpoints ID50 value was very low (< 10 μg/mL) so OTA was classified as a strong teratogen. IC50/ ID50 ratios <2 pointed out that with harmful action of OTA the basic cytotoxicity should be connected.
Highlights
The developing central nervous system (CNS) is much more vulnerable to injury from toxic agents than the adult CNS
Ochratoxin A (OTA) is a mycotoxin that occurs in improperly stored food products and is produced by some Aspergillus and Penicillium species
The aim of this study was to gain more insight into the influence of ochratoxin A (OTA) on the embryonic neural cells cultured in high density “micromass cultures”
Summary
The developing central nervous system (CNS) is much more vulnerable to injury from toxic agents than the adult CNS. Ochratoxin A (OTA) is a mycotoxin that occurs in improperly stored food products and is produced by some Aspergillus and Penicillium species. It primarily disrupts renal function and has been discussed as a causative factor in the human disease “Balkan endemic nephropathy” (BEN) and in the development of urinary tract tumours in humans [5]. OTA is known to cause a wide range of other toxic effects, including carcinogenicity, hepatotoxicity, neurotoxicity, and teratogenicity [6, 7] as well as immunomodulating and often immunosuppressive action [8, 9]
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