Selective toxicity of ochratoxin A in primary cultures from different brain regions.
Ochratoxin A (OTA) is a mycotoxin produced by moulds from the Aspergillus and Penicillium genera. It is a natural contaminant of a wide variety of both human and animal foodstuffs. Via dietary intake, OTA passes into the blood of both humans and animals and accumulates in several organs, such as the kidney and the brain with selective toxicity in the ventral mesencephalon and in the cerebellum. In order to confirm the regional selectivity to OTA cytotoxicity in rat brain, investigations were designed to study the mechanism of the cytotoxicity of OTA in primary cultures of the above-mentioned structures (ventral mesencephalon and cerebellum), and to compare their sensitivity to the toxin. Protein and DNA synthases, lactate dehydrogenase (LDH) release and production of malondialdehyde (MDA) were assayed in astrocytes and neurones of the selected structures in the presence of OTA. After 48 h incubation, OTA (10-150 microM) induced an inhibition of protein and DNA syntheses in a concentration-dependent manner with a selective higher toxicity in the cells of the ventral mesencephalon [50% inhibitory concentrations (IC50) of protein and DNA syntheses were 14 +/- 2 microM for neurones and 40 +/- 5 microM for astrocytes] compared to the cerebellum values (24 +/- 7 microM for neurones and 69 +/- 9 microM for astrocytes). In parallel, a significant increase in levels of MDA and LDH release were noted. Altogether these results indicate that OTA is also a neurotoxic substance in addition to its well-documented nephrotoxicity and that the effects are likely to be restricted within particular structures of the brain.
Belmadani
A
A
Laboratory of Toxicology and Applied Hygiene, University Victor-Segalen Bordeaux II, France.
Steyn
P S
PS
Tramu
G
G
Betbeder
A M
AM
Baudrimont
I
I
Creppy
E E
EE
D015104:3,4-Methylenedioxyamphetamine / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000196:embryology; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects / Q000196:embryology; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005260:Female; D007668:Kidney / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008636:Mesencephalon / Q000187:drug effects / Q000196:embryology; D009183:Mycotoxins / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009793:Ochratoxins / Q000633:toxicity*; D009928:Organ Specificity; D011247:Pregnancy; D014176:Protein Biosynthesis; D051381:Rats; D017208:Rats, Wistar
D009183:Mycotoxins; D009793:Ochratoxins; C025589:ochratoxin A; D015104:3,4-Methylenedioxyamphetamine; D004247:DNA; D007770:L-Lactate Dehydrogenase