Can low level exposure to ochratoxin-A cause parkinsonism?

[Guest guest]

Can low level exposure to ochratoxin-A cause parkinsonism?

Authors:

Sava V

Reunova O

Velasquez A

-Ramos J

Author Address: University of South Florida, Tampa, FL 33612, USA.

Source: J Neurol Sci. 2006, Nov 1; 249(1):68-75. [Journal of the

neurological sciences]

http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~vUnAFq:511

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 LD(50)) 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.

Medical Subject Headings (MeSH):

3,4-Dihydroxyphenylacetic Acid/metabolism

Age Factors

Age of Onset

Animals

Antioxidants/metabolism

Carcinogens/toxicity

Corpus Striatum/*drug effects/metabolism/physiopathology

DNA Glycosylases/drug effects/metabolism

DNA Repair/drug effects/physiology

Disease Models, Animal

Dopamine/metabolism

Dose-Response Relationship, Drug

Enzyme Activation/drug effects/physiology

Male

Mice

Mice, Inbred ICR

Ochratoxins/*toxicity

Oxidative Stress/drug effects/physiology

Parkinsonian Disorders/*chemically induced/physiopathology

Up-Regulation/drug effects/physiology

CAS Registry Numbers:

Antioxidants (0)

Carcinogens (0)

Ochratoxins (0)

3,4-Dihydroxyphenylacetic Acid (102-32-9)

ochratoxin A (303-47-9)

Dopamine (51-61-6)

DNA Glycosylases (EC 3.2.2.-)

Ogg1 protein, mouse (EC 3.2.2.-)

Language: English

International Standard Serial Number: 0022-510X (Print)

Publication Types:

Journal Article

Research Support, U.S. Gov't, Non-P.H.S.

Entry Month: June, 2006

Title Abbreviation: J Neurol Sci

Year of Publication: 2006

Last Revision Date: November 6, 2006

Medline Citation: NLM

Country: Netherlands

Citation Subset: IM

Medline Title Abbreviation: Journal of the neurological sciences

Article Date: 20060714

Stat: MEDLINE

Document Number: medline/16844142