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Age-related susceptibility to 3,3'-iminodipropionitrile-induced olfactory mucosal damage |
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| Authors: | Genter M B Ali S F |
| Institution: | * Department of Molecular and Cellular Physiology, University of Cincinnati, Cincinnati, OH 45267-0576 USA † Neurochemistry Laboratory, Division of Neurotoxicology, National Center for Toxicological Research, Jefferson, AR 72079-9502 USA c Departments of Biochemistry and Molecular Biology and Pharmacology/Toxicology, University of Arkansas Medical Sciences, Little Rock, AR 72205 USA |
| Abstract: | 3,3′-Iminodipropionitrile (IDPN) causes degeneration of the olfactory mucosa (OM) in rodents following systemic exposure. Approximately 30% of the OM degenerates in 21-day- and 10-week-old rats following a single 200 or 400 mg/kg intraperitoneal (i.p.) dose of IDPN, whereas 100% olfactory mucosal degeneration occurred in 21-month-old rats. Age-related changes in the flavin-containing monooxygenases (FMOs) or heat shock protein 70 (HSP70) were hypothesized to be responsible for altered olfactory mucosal susceptibility to IDPN. FMO activity in OM was higher than in liver in rats up to 40 weeks of age. Western blots of OM and liver revealed no change in FMO1 protein; however, FMO2, 3, and 5 decreased in olfactory microsomes with age. FMO3 and FMO5 increased in liver microsomes with age. Heat shock protein 70 did not differ between 10-week- and 10-month-old rats in either tissue. The mechanism underlying the increased susceptibility of older rats is likely a complex interaction between the activities of one or more of the enzymes involved in IDPN metabolism in OM and liver. |
| Keywords: | Aging heat shock protein Cytochrome P450 3 3′-Iminodipropionitrile (IDPN) Eosinophilic globules olfactory mucosa Flavin-containing monooxygenases (FMO) Susceptibility |
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