Intranasal instillation of aflatoxin B(1) in rats: bioactivation in the nasal mucosa and neuronal transport to the olfactory bulb.
Aflatoxin B(1) (AFB(1)) may be present in moldy dust. Inhalation of contaminated dust particles may result in high local exposure of the nasal mucosa. The present study was designed to assess bioactivation and toxicity of AFB(1) in the nasal mucosa after intranasal administration of the mycotoxin in rats and also to examine if translocation of the mycotoxin occurs from the nasal mucosa to the brain along olfactory neurons. Female Sprague-Dawley rats were given (3)H-AFB(1) (0.2, 1 or 20 microg) intranasally and were sacrificed at various intervals (1 h to 20 d). Tissues were examined autoradiographically or histopathologically. Quantitative data were obtained by beta-spectrometry in rats given (3)H-AFB(1) intranasally or orally (for comparison). The data indicated that intranasal administration of AFB(1) resulted in formation of tissue-bound metabolites in sustentacular cells, in some cells of Bowman's glands, and in a population of neuronal cells in the olfactory mucosa, whereas in the respiratory nasal mucosa, there was selective bioactivation of AFB(1) in mucous cells. Intranasal instillation of 20 microg AFB(1) resulted in disorganized undulating olfactory epithelium, with injured neuronal and sustentacular cells. In the respiratory epithelium, there was selective destruction of mucous cells. beta-Spectrometry and autoradiography with tape-sections of the head of rats given (3)H-AFB(1) intranasally indicated transport of AFB(1) and/or AFB(1) metabolites along the axons of the primary olfactory neurons to their terminations in the glomeruli of the olfactory bulb. The data indicate that the materials transported in the olfactory nerves represent AFB(1) and/or some of its nonreactive metabolites. It is concluded that application of AFB(1) on the nasal mucosa in rats results in high local bioactivation of the mycotoxin in this tissue and translocation of AFB(1) and/or its metabolites to the olfactory bulb.
Larsson
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P
Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala. pia.larsson@farmtox.slu.se
Tjälve
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H
D000281:Administration, Intranasal; D000284:Administration, Oral; D016604:Aflatoxin B1 / Q000493:pharmacokinetics* / Q000633:toxicity; D000818:Animals; D001345:Autoradiography; D001692:Biological Transport; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009830:Olfactory Bulb / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D009832:Olfactory Nerve / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012588:Scintillation Counting
D016604:Aflatoxin B1