Metabolism‐Dependent Toxicity of Methimazole in the Olfactory Nasal Mucosa
Abstract
Abstract:In mice given a single intraperitoneal injection of the antithyroid drug methimazole (0.44 mmol/kg; 50 mg/kg) detachment of the olfactory neuroepithelium and necrosis of the Bowman’glands in the lamina propria was observed 24 hr after administration. Three days after administration there was an atypical epithelium throughout the olfactory region and the Bowman's glands had disappeared. Pretreatment with the olfactory cytochrome P450 inhibitor metyrapone protected against the methimazole‐induced changes at this site. In mice injected with the methimazole analogues 1‐methylimi‐dazole or 4‐methylimidazole (0.44 mmol/kg; 36 mg/kg) or the antithyroid drug propylthiuracil (0.22 mmol/kg; 38 mg/kg) no morphological changes were observed in the olfactory mucosa. The results suggest that methimazole‐induced toxicity in the olfactory mucosa is related to metabolism‐dependent changes of the thiol group.
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Methimazole causes degeneration of the nasal epithelium in rodents.
“Methimazole causes degeneration of the nasal epithelium in rodents47.”
From Chlamydia pneumoniae can infect the central nervous system via the olfactory and trigeminal nerves and contributes to Alzheimer’s disease risk (2022) · cites this paper as [47]
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Chacko, A., Delbaz, A., Walkden, H., Basu, S., Armitage, C. W., Eindorf, T., Trim, L. K., Miller, E., West, N. P., St John, J. A., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-06749-9 · Cited by 65 · see citing works
- Authors
- Brittebo, E. B.
- Affiliations
- Lund University (SE)
- Corresponding author
- Brittebo, Eva B.
- ORCID
- Brittebo, Eva B.
- Venue
- Pharmacology & Toxicology
- Publisher
- Wiley
- Published
- 1995-01
- Volume
- 76
- Issue
- 1
- Pages
- 76-79
- ISSN
- 0901-9928 (ISSN-L)
- OpenAlex
- W2071103277
- Cited by
- 69
- References
- 0
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 1 · 2018: 4 · 2017: 2 · 2016: 1 · 2015: 3 · 2014: 3 · 2013: 4 · 2012: 2
- FWCI
- 1.85
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacology & Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Skogs- och Jordbrukets Forskningsråd
- Naturvårdsverket
- Topics
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Keywords
- methimazole, olfactory epithelium, Bowman's glands, drug toxicity, cytochrome P450, metyrapone, propylthiouracil, 1-methylimidazole, 4-methylimidazole, antithyroid drugs, nasal mucosa
- MeSH terms
- Animals, Cytochrome P-450 Enzyme System, Drug Interactions, Female, Methimazole, Olfactory Mucosa, Propylthiouracil, Mice, Cytochrome P-450 Enzyme Inhibitors
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