The neurotoxic effects of ochratoxin-A are reduced by protein binding but are not affected by l-phenylalanine.
Recent in vivo investigations indicate that the mycotoxin ochratoxin A (OTA) is a neurotoxicant during prenatal stages. In line with in vivo data, in our embryonic chick brain and neural retina cell cultures the markers for neuritic outgrowth and differentiation (NF68 and 160 kDa, MAP2 and MAP5) were especially negatively affected. In vivo OTA is nearly completely bound to serum constituents. In our culture system binding of OTA to BSA evoked a significant shift of the concentration-effect relationships in meningeal and brain cell cultures. As a result of the albumin binding the OTA IC5 and IC50 values of all parameters increased by nearly the same value (about 15-fold in brain and 32-fold in meningeal cell cultures). One of the mechanisms responsible for OTA toxicity is thought to be the competitive inhibition versus Phe of Phe-dependent enzymes. Therefore, in addition, we investigated the effects of l-phenylalanine (Phe) and its influence on OTA toxicity in brain and neural retina cell cultures. Phe itself was found to differently affect brain and neural retina cell cultures. However, in both cultures OTA toxicity is not diminished by Phe. Therefore, our data indicate that at least in our cultures competition with Phe-dependent processes does not play a role in OTA toxicity.
Bruinink
A
A
Institute of Toxicology, ETH & Uni Zürich, Schorenstrasse 16, Schwerzenbach, CH-8603, Switzerland. brinink@biocomp.mat.ethz.ch
Sidler
C
C
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects / Q000196:embryology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D008578:Meninges / Q000187:drug effects / Q000196:embryology; D009183:Mycotoxins / Q000633:toxicity*; D009498:Neurotoxins / Q000633:toxicity*; D009793:Ochratoxins / Q000633:toxicity*; D010649:Phenylalanine / Q000494:pharmacology*; D011485:Protein Binding; D012160:Retina / Q000187:drug effects / Q000196:embryology; D012710:Serum Albumin, Bovine / Q000378:metabolism*; D013237:Stereoisomerism
D009183:Mycotoxins; D009498:Neurotoxins; D009793:Ochratoxins; C025589:ochratoxin A; D012710:Serum Albumin, Bovine; D010649:Phenylalanine