PURIFICATION AND COMPARATIVE NEUROTOXICITY OF THE TRICHOTHECENES

March 13, 2011

PURIFICATION AND COMPARATIVE NEUROTOXICITY OF THE TRICHOTHECENES SATRATOXIN G

AND RORIDIN L2 FROM STACHYBOTRYS CHARTARUM

2010 Aug;116(2):433-40. Epub 2010 May 13.

Kinetics of satratoxin g tissue distribution and excretion following intranasal

exposure in the mouse.

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Abstract

Intranasal exposure of mice to satratoxin G (SG), a macrocyclic trichothecene

produced by the indoor air mold Stachybotrys chartarum, selectively induces

apoptosis in olfactory sensory neurons (OSNs) of the nose and brain. The purpose

of this study was to measure the kinetics of distribution and clearance of SG in

the mouse. Following intranasal instillation of female C57B16 mice with SG (500

microg/kg bw), the toxin was detectable from 5 to 60 min in blood and plasma,

with the highest concentrations, 30 and 19 ng/ml, respectively, being observed

at 5 min. SG clearance from plasma was rapid and followed single-compartment

kinetics (t(1/2) = 20 min) and differed markedly from that of other tissues. SG

concentrations were maximal at 15-30 min in nasal turbinates (480 ng/g), kidney

(280 ng/g), lung (250 ng/g), spleen (200 ng/g), liver (140 ng/g), thymus (90

ng/g), heart (70 ng/g), olfactory bulb (14 ng/g), and brain (3 ng/g). The

half-lives of SG in the nasal turbinate and thymus were 7.6 and 10.1 h,

respectively, whereas in other organs, these ranged from 2.3 to 4.4 h. SG was

detectable in feces and urine, but cumulative excretion over 5 days via these

routes accounted for less than 0.3% of the total dose administered. Taken

together, SG was rapidly taken up from the nose, distributed to tissues involved

in respiratory, immune, and neuronal function, and subsequently cleared.

However, a significant amount of the toxin was retained in the nasal turbinate,

which might contribute to SG's capacity to evoke OSN death

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