Zinc gluconate toxicity in wild-type vs. MT1/2-deficient mice
| Autor: | Heidi Hsieh, Michael C. Horwath, Mary Beth Genter |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Pathology Anosmia Mice Transgenic Olfaction Toxicology Gluconates Article 03 medical and health sciences Olfactory mucosa Mice Olfaction Disorders 0302 clinical medicine Olfactory Mucosa In vivo Internal medicine Proliferating Cell Nuclear Antigen medicine Matrix Metalloproteinase 14 Metallothionein Animals Administration Intranasal Dose-Response Relationship Drug Chemistry General Neuroscience Matrix Metalloproteinase 15 Thiazoles 030104 developmental biology Endocrinology medicine.anatomical_structure 030220 oncology & carcinogenesis Toxicity Nasal administration medicine.symptom Olfactory epithelium |
| Zdroj: | Neurotoxicology. 58 |
| ISSN: | 1872-9711 |
| Popis: | Previous studies have suggested that oral zinc supplementation can help reduce the duration of the common cold; however, the use of intranasal (IN) zinc is strongly associated with anosmia, or the loss of the sense of smell, in humans. Prior studies from this lab showed that upregulation of metallothioneins (MT) is a rapid and robust response to zinc gluconate (ZG). Therefore, we assessed the role of MT in the recovery of nasal epithelial damage resulting from IN zinc administration. The main studies in this investigation used a high dose of ZG (170 mM) to ensure ablation of the olfactory mucosa, so that the progression of histological and functional recovery could be assessed. In vivo studies using wild-type, MT1/2 knockout mice (MT KO), and heterozygotes administered ZG by IN instillation showed profound loss of the olfactory mucosa in the nasal cavity. Recovery was monitored, and a lower percentage of the MT KO mice were able to smell 28 d after treatment; however, no significant difference was observed in the rate of cell proliferation in the basal layer of the olfactory epithelium between MT KO and wild-type mice. A lower concentration of ZG (33 mM), equivalent to that found in homeopathic IN ZG preparations, also caused olfactory epithelial toxicity in mice. These studies suggest that the use of zinc in drug formulations intended for IN administration in humans must be carefully evaluated for their potential to cause olfactory functional deficits. |
| Databáze: | OpenAIRE |
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