Novel toxicity by macrocyclic trichothecens mycotoxins
Trichothecenes are a family of over 200 sesquiterpenoid mycotoxins produced by <i>Fusarium</i>, <i>Stachybotrys</i>, <i>Myrothecium</i> and other molds. Satratoxin G (SG) is a macrocyclic trichothecene mycotoxins produced by <i>Stachybotrys chartarum</i>, the "black mold" reported to illnesses associated with water-damaged buildings. We found that single instillation of macrocyclic trichothecenes SG or Roridin A (RA) exposure in C57Bl/6 female mice specifically targeted olfactory sensory neurons (OSNs) in the olfactory epithelium in the mouse nose. The OSN death was verified by imuunohistochemial staining of activated caspase-3, electronmicroscopic analysis, Real Time PCR method for the expression of pro-apoptotic genes. The results suggested that SG-induced OSN death was via apoptosis. The death of OSN caused the atrophy of the olfactory epithelium. The maximum atrophy of the epithelium was observed at 3 days after single instillation of SG (500 μg/kg bw). After 7 days postinstillation (PI), the thickness of the olfactory epithelium recovered partially with the recruitment of fresh OSNs in the epithelium. When the mice are instilled with lower doses of SG (100 μg/kg bw) for 5 consecutive days it also induces same degree of atrophy and apoptosis, suggesting that these effects are cumulative. SG also induced an influx of mucosubstances filled with neutrophils (neutrophilic rhinitis) in the airways at 24 hr PI. Proinflammatory cytokines and the chemokine genes were upregulated at 24 hr PI in both the ethmoid turbinates of the nasal airways and the adjacent olfactory bulb of the brain. Marked atrophy of the olfactory nerve and glomerular layers of the olfactory bulb was also detectable by 7 days PI along with mild neutrophilic encephalitis.
マイコトキシン 58(1), 53-60, 2008-01-31
Japanese Society of Mycotoxicology