F. Monnettschudi et al., EFFECTS OF THE NATURALLY-OCCURRING FOOD MYCOTOXIN OCHRATOXIN-A ON BRAIN-CELLS IN CULTURE, Neurotoxicology, 18(3), 1997, pp. 831-839
The potential of ochratoxin A (OTA) to damage brain cells was studied
by using a three-dimensional cell culture system as model for the deve
loping brain. Aggregating cell cultures of foetal rat telencephalon we
re tested either during an early developmental period, or during a pha
se of advanced maturation, over a wide range of OTA concentrations (0.
4 nM to 50 mu M). By monitoring changes in activities of cell type-spe
cific enzymes (ChAt and GAD, for cholinergic and GABAergic neurones, r
espectively, GS for astrocytes and CNP for oligodendrocytes), the conc
entration-dependent toxicity and neurodevelopmental effects of OTA wer
e determined OTA proved to be highly toxic, since a 10-day treatment a
t 50 nM caused a general cytotoxicity in both mature and immature cult
ures. At 10 nM of OTA, cell type-specific effects were observed : in i
mmature cultures, a loss in neuronal and oligodendroglial enzyme activ
ities, and an increase in the activity of the astroglial marker glutam
ine synthetase were found. Furthermore, at 2 and 10 nM of OTA, a clust
ering of microglial cells was observed. In mature cultures, OTA was so
mewhat less potent, but caused a similar pattern of toxic effects. A 2
4 h-treatment with OTA resulted in a concentration-dependent decrease
in protein synthesis, with IC50 values of 25 nM and 33 nM for immature
and mature cultures respectively. Acute (24 h) treatment at high OTA
concentrations (10 to 50 mu M) caused a significant increase in reacti
ve oxygen species formation, as measured by the intracellular oxidatio
n of 2',7'-dichloroflourescin. These results suggest that OTA has the
potential to be a potent toxicant to brain cells, and that its effects
at nanomolar concentrations are primarily due to the inhibition of pr
otein synthesis, whereas ROS seem not to be involved in the toxicity m
ediated by a chronic exposure to OTA at such low concentrations. (C) I
ntox Press, Inc. 1997.