Abstract
Mycotoxins are fungal metabolites with pharmacological activities that have been utilized
in the production of antibiotics, growth promoters, and other classes of drugs. Some
mycotoxins have been developed as biological and chemical warfare agents. Bombs and
ballistic missiles loaded with aflatoxin were stockpiled and may have been deployed
by Iraq during the first Gulf War. In light of the excess incidence of amyotrophic
lateral sclerosis (ALS) in veterans from Operation Desert Storm, the potential for
delayed neurotoxic effects of low doses of mycotoxins should not be overlooked. Ochratoxin-A
(OTA) is a common mycotoxin with complex mechanisms of action, similar to that of
the aflatoxins. Acute administration of OTA at non-lethal doses (10% of the LD50) have been shown to increase oxidative DNA damage in brain up to 72 h, with peak
effects noted at 24 h in midbrain (MB), caudate/putamen (CP) and hippocampus (HP).
Levels of dopamine (DA) and its metabolites in the striatum (e.g., CP) were shown
to be decreased in a dose-dependent manner. The present study focused on the effects
of chronic low dose OTA exposure on regional brain oxidative stress and striatal DA
metabolism. Continuous administration of low doses of OTA with implanted subcutaneous
Alzet minipumps caused a small but significant decrease in striatal DA levels and
an upregulation of anti-oxidative systems and DNA repair. It is possible that low
dose exposure to OTA will result in an earlier onset of parkinsonism when normal age-dependent
decline in striatal DA levels are superimposed on the mycotoxin-induced lesion.
Keywords
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© 2006 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
