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Bioactivation and transport of foreign materials in the olfactory system

Persson, Eva (2003). Bioactivation and transport of foreign materials in the olfactory system. Diss. (sammanfattning/summary) Uppsala : Sveriges lantbruksuniv., Acta Universitatis agriculturae Sueciae. Veterinaria, 1401-6257 ; 145
ISBN 91-576-6361-0
[Doctoral thesis]

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Abstract

The brain is protected from circulating toxicants by the blood-brain barrier. In the olfactory mucosa the primary olfactory neurons are in contact with the external environment in the nasal cavity and these neurons also reach the olfactory bulbs of the brain. Uptake in the olfactory epithelium and transport along the olfactory neurons may therefore pose an alternative route of entry for foreign materials to the brain. The olfactory mucosa also contains many metabolising enzymes, which may participate in the bioactivation of xenobiotics in this tissue. The aim of the present thesis was to increase the knowledge of the olfactory system as a site of bioactivation and a route of entry to the brain of foreign materials. Studies in horses showed that aflatoxin B1 (AFB1) is bioactivated in the olfactory mucosa to DNA-binding metabolites. The localization of cells with bioactivating capacity correlated with the localization of cells containing the cytochrome P450 (CYP)-enzymes CYP 3A4 and CYP 2A6, which are known to be involved in the bioactivation of AFB1. Studies in rats showed that intranasal administration of benzo(a)pyrene (BP) leads to a bioactivation of the compound in some cells in the olfactory mucosa and a transfer of BP and/or BP-metabolites to the olfactory bulbs of the brain. Studies in rats and pike showed that cobalt and zinc are taken up in the olfactory mucosa and transported along the primary olfactory neurons to their terminations in the olfactory bulbs. These metals also continue to the interior of the bulb and to the anterior parts of the olfactory cortex. Cadmium was shown to be transported bound to metallothionein in the olfactory system of rats and pikes. It is concluded that the olfactory system is an important site of bioactivation of xenobiotics and a route by which foreign materials may gain access to the brain.

Authors/Creators:Persson, Eva
Title:Bioactivation and transport of foreign materials in the olfactory system
Year of publishing :2003
Volume:145
Number of Pages:35
Papers/manuscripts:
NumberReferences
ALLI. Larsson, P., Persson, E., Tydén, E. & Tjälve, H. Cell-specific activation of aflatoxin B1 correlates with presence of some cytochrome P450 enzymes in the olfactory and respiratory tissues in horse. Accepted for publication in Research in Veterinary Science II. Persson, E., Larsson, P. & Tjälve, H. 2002. Cellular activation and neuronal transport of intranasally instilled benzo(a)pyrene in the olfactory system of rats. Toxicology letters 133, 211-219. III. Persson, E., Henriksson, J. & Tjälve, H. Uptake of cobalt from the nasal mucosa into the brain via olfactory pathways in rats. Manuscript IV. Persson, E., Henriksson, J., Tallkvist, J., Rouleau, C. & Tjälve, H. Transport and subcellular distribution of intranasally administered zinc in the olfactory system of rats and pikes. Manuscript V. Tallkvist, J., Persson, E., Henriksson, J. & Tjälve, H. 2002. Cadmium-metallothionein interactions in the olfactory pathways of rats and pikes. Toxicological sciences 67, 108-113.
Place of Publication:Uppsala
Publisher:Institutionen för farmakologi och toxikologi, Sveriges lantbruksuniversitet
ISBN for printed version:91-576-6361-0
ISSN:1401-6257
Language:English
Publication Type:Doctoral thesis
Full Text Status:Public
Keywords:olfactory pathway, inhalation, metal exposure, mycotoxin, intranasally, autoradiography, CNS
URN:NBN:urn:nbn:se:slu:epsilon-171
Permanent URL:
http://urn.kb.se/resolve?urn=urn:nbn:se:slu:epsilon-171
ID Code:204
Department:(VH)
Deposited By: Staff Epsilon
Deposited On:01 Apr 2003 00:00
Metadata Last Modified:02 Dec 2014 10:02

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