New study on potentiation of trichothecene mycotoxins by lipopolysaccharide endotoxins (also commonly found in damp buildings)

[Guest guest]

This adds more evidence to the growing body of proof that endotoxins

found in damp building bacteria strongly potentiate the effects of

mycotoxins from the molds in damp buildings.

However, do ACOEM, AAAAI, etc. consider or ever even mention this? NO!

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ToxSci Advance Access published online on May 4, 2007

Toxicological Sciences, doi:10.1093/toxsci/kfm102

Neurotoxicity and Inflammation in the Nasal Airways of Mice Exposed to

the Macrocyclic Trichothecene Mycotoxin Roridin A:

Kinetics and Potentiation by Bacterial Lipopolysaccharide Co-Exposure

Zahidul Islam, Chidozie J. Amuzie, Jack R. Harkema and J.

Pestka (note 1),

1 To whom correspondence should be addressed at 234 G.M. Trout

Building, Michigan State University, East Lansing, MI 48824-1224. Fax:

517-353-8963. E-mail: pestka@....

Received February 7, 2007; revision received April 27, 2007; accepted

April 27, 2007

Macrocyclic trichothecene mycotoxins produced by indoor air molds

potentially contribute to symptoms associated with damp building

illnesses. The purpose of this investigation was to determine (1) the

kinetics of nasal inflammation and neurotoxicity after a single

intranasal instillation of roridin A (RA), a representative

macrocyclic trichothecene, and (2) the capacity of lipopolysaccharide

(LPS) to modulate RA's effects. C57Bl/6 female mice were intranasally

instilled once with 50 µl of RA (500 µg/kg bw) in saline or saline

only and then nose and brain tissues were collected over 72 h and

processed for histopathologic and mRNA analysis. RA induced apoptosis

specifically in olfactory sensory neurons (OSNs) after 24 h PI causing

marked atrophy of olfactory epithelium (OE) that was maximal at 72 h

PI. Concurrently, there was marked bilateral atrophy of olfactory

nerve layer of the olfactory bulbs (OBs) of the brain. In the ethmoid

turbinates, upregulated mRNA expression of the proapoptotic gene FAS

and the proinflammatory cytokines TNF-{alpha}, IL-6, IL-1 and MIP-2

was observed from 6 to 24 h PI, whereas expression of several other

proapoptotic genes (PKR, p53, Bax, and CAD) was detectable only at 24

h PI.

Simultaneous exposure to LPS (500 ng/kg bw) and a lower dose of RA

(250 µg/kg bw) magnified RA-induced proinflammatory gene expression,

apoptosis and inflammation in the nasal tract.

Taken together, the results suggest that RA markedly induced FAS and

proinflammatory cytokine expression prior to evoking OSN apoptosis and

OE atrophy and that RA's effects were augmented by LPS.

Key Words: trichothecene; mycotoxin; apoptosis; neurotoxicity;

inflammation; endotoxin.