Methimazole-induced damage in the olfactory mucosa: effects on ultrastructure and glutathione levels

Ulrika Bergström1, Anna Giovanetti, Elena Piras

  • 1Department of Pharmacology and Toxicology, SLU, Box 573, SE-751 23 Uppsala, Sweden. Ulrika.Bergstrom@ebc.uu.se

Toxicologic Pathology
|July 10, 2003
PubMed

Insights

Methimazole, an antithyroid drug, depletes glutathione in the olfactory mucosa, causing significant cellular damage. This damage, observed via electron microscopy, affects Bowman's glands and sustentacular cells, leading to neuroepithelium disorganization.

Area of Science:

  • Toxicology
  • Neuroscience
  • Cell Biology

Background:

  • Methimazole is an antithyroid drug known to cause olfactory dysfunction in humans and rodents.
  • Glutathione is a key cellular antioxidant, and its depletion can lead to oxidative stress and cell damage.

Purpose of the Study:

  • To investigate the role of glutathione in methimazole-induced olfactory mucosa damage in mice.
  • To characterize the early cellular changes in the olfactory mucosa following methimazole administration using transmission electron microscopy (TEM).

Main Methods:

  • Mice were administered varying doses of methimazole intraperitoneally.
  • Olfactory mucosa (OM) and liver nonprotein sulfhydryl groups (NP-SH), primarily glutathione, were measured.
  • Transmission electron microscopy (TEM) was used to examine cellular damage in the OM at 1, 2, and 4 hours post-administration.

Main Results:

  • Methimazole induced a dose-dependent decrease in OM NP-SH levels, while hepatic NP-SH remained unaffected.
  • TEM revealed early damage to Bowman's glands (BG) excretory duct cells, including endoplasmic reticulum dilation and mitochondrial swelling, within 1 hour.
  • Sustentacular cell degeneration and disorganization of the neuroepithelium were observed at later time points, with damage to BG appearing secondary to duct and sustentacular cell injury.

Conclusions:

  • Glutathione depletion in the olfactory mucosa is a key mechanism in methimazole-induced toxicity.
  • Early and severe damage to Bowman's glands and sustentacular cells precedes neuroepithelial disorganization.
  • Methimazole serves as an olfactory toxicant, with its effects mediated by glutathione depletion and subsequent cellular damage in the olfactory system.

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