Differences in neurotoxic effects of ochratoxin A, ochracin and ochratoxin-alpha in vitro.
The mycotoxin ochratoxin A (OTA) is a chlorinated dihydroisocoumarin derivative connected through an amide-bond to L-phenylalanine. In a previous study we could show that competition with L-phenylalanine-dependent processes does not play a role in OTA neurotoxicity. To test whether the isocoumarin part is responsible for the neurotoxic effects, we determined in the present study the effects of the hydrolysis product of OTA, ochratoxin-alpha (OTalpha), and of ochracin on embryonic chick brain cell cultures. In addition, we investigated the interaction between OTA and ochracin regarding the neurotoxic effects. We report here that OTalpha did not affect brain cell cultures at concentrations up to 15 microM. With the exception of a small (20%) but significant reduction in cell culture, cellular protein at concentrations above 0.3 microM, in our cell cultures' cell function, as defined by neutral red uptake and MTT-dehydrogenase activity, was only reduced by high OTalpha concentrations (1 mM). Addition of 0.1 microM OTA increased ochracin cytotoxicity as defined by latter parameters. No effects on cell culture NF68kD content could be detected. The results are discussed with regard to the existence of an OTA target interaction binding site.
Institute of Toxicology, ETH & Uni Zürich, Schorenstrasse 16, CH-8603 Schwerzenbach, Switzerland.
A
A
Bruinink
T
T
Rasonyi
C
C
Sidler
D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D004396:Coloring Agents; D049934:Isocoumarins; D009183:Mycotoxins / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity*; D009793:Ochratoxins / Q000633:toxicity*; D013329:Structure-Activity Relationship; D013778:Tetrazolium Salts; D013844:Thiazoles
D004396:Coloring Agents; D049934:Isocoumarins; D009183:Mycotoxins; D009498:Neurotoxins; D009793:Ochratoxins; D013778:Tetrazolium Salts; D013844:Thiazoles; C000426:5-chloro-8-hydroxy-3,4-dihydro-3-methylisocoumarin-7-carboxylic acid; C025589:ochratoxin A; C022616:thiazolyl blue; C120538:ochracin