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Toxicologic Pathology
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Methimazole-Induced Damage in the Olfactory Mucosa: Effects on Ultrastructure and Glutathione Levels

Ulrika Bergström

Department of Pharmacology and Toxicology, SLU, Box 573, SE-751 23 Uppsala, Sweden, Ulrika.Bergstrom{at}ebc.uu.se

Anna Giovanetti

ENEA ION IRP, CR Casaccia, Via Anguillarese 301, 00060 Rome, Italy

Elena Piras

Department of Pharmaceutical Biosciences, Uppsala University, P.O. Box 594, SE-751 24 Uppsala, Sweden

Eva B. Brittebo

Department of Pharmaceutical Biosciences, Uppsala University, P.O. Box 594, SE-751 24 Uppsala, Sweden

Methimazole is an antithyroid drug that can induce loss of smell and taste in humans. It is also an olfactory toxicant in rodents. The aim of the present study was to examine involvement of glutathione in methimazole-induced damage of the olfactory mucosa (OM) of mice, and to study early onset of this damage using transmission electron microscopy (TEM). We found that an intraperitoneal dose of methimazole induced a dose-dependent decrease of nonprotein sulfhydryl groups (NP-SH; mainly glutathione) in the OM. Hepatic NP-SH was not decreased. One hour after administration (50 mg/kg), TEM demonstrated an extensive damage to acinar and intraepithelial excretory duct cells of Bowman's glands (BG) including dilatation of the endoplasmic reticulum and mitochondrial swelling. Furthermore, large vacuoles were noted in basal intraepithelial duct cells. After 2 hours there were ruptures of secretory granule membranes in BG and mitochondrial swelling and degeneration of sustentacular cells. The basal cells were less damaged. After four hours the neuroepithelium was disorganized although the columnar organization of neurons was largely intact. The acinar organization of the BG was frequently lost. The subsequent detachment of the neuroepithelium is suggested to be secondary to extensive damage of BG excretory ducts and sustentacular cells.

Key Words: Olfactory neuroepithelium • glutathione • transmission electron microscopy • mice • Bowman's glands • sustentacular cells • methimazole.

References

Toxicologic Pathology, Vol. 31, No. 4, 379-387 (2003)
DOI: 10.1080/01926230390201101
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[Abstract] [Full Text] [PDF]

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