Neurotoxic potential and cellular uptake of T-2 toxin in human astrocytes in primary culture.
The trichothecene mycotoxin T-2 toxin, which is produced by fungi of the Fusarium species, is a worldwide occurring contaminant of cereal based food and feed. The cytotoxic properties of T-2 toxin are already well described with apoptosis being a major mechanism of action in various cell lines as well as in primary cells of different origin. However, only few data on neurotoxic properties of T-2 toxin are reported so far, but in vivo studies showed different effects of T-2 toxin on behavior as well as on levels of brain amines in animals. To further investigate the cytotoxic properties of T-2 toxin on cells derived from brain tissue, normal human astrocytes in primary culture (NHA) were used in this study. Besides studies of cytotoxicity, apoptosis (caspase-3-activation, Annexin V) and necrosis (LDH-release), the cellular uptake and metabolism of T-2 toxin in NHA was analyzed and compared to the uptake in an established human cell line (HT-29). The results show that human astrocytes were highly sensitive to the cytotoxic properties of T-2 toxin, and apoptosis, induced at low concentrations, was identified for the first time as the mechanism of toxic action in NHA. Furthermore, a strong accumulation of T-2 toxin in NHA and HT-29 cells was detected, and T-2 toxin was subjected to metabolism leading to HT-2 toxin, a commonly found metabolite after T-2 toxin incubation in both cell types. This formation seems to occur within the cells since incubations of T-2 toxin with cell depleted culture medium did not lead to any degradation of the parent toxin. The results of this study emphasize the neurotoxic potential of T-2 toxin in human astrocytes at low concentrations after short incubation times.
Institute of Food Chemistry, Westfälische Wilhelms-Universität Münster, Corrensstrasse 45, Münster, Germany.
Maria
M
Weidner
Marlies
M
Lenczyk
Gerald
G
Schwerdt
Michael
M
Gekle
Hans-Ulrich
HU
Humpf
D017304:Annexin A5 / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D002523:Edible Grain / Q000382:microbiology; D004789:Enzyme Activation / Q000187:drug effects; D005670:Fusarium / Q000378:metabolism*; D019073:HT29 Cells; D006801:Humans; D013605:T-2 Toxin / Q000031:analogs & derivatives / Q000378:metabolism / Q000633:toxicity*
D017304:Annexin A5; D053148:Caspase 3; D013605:T-2 Toxin; C012351:HT-2 toxin