title: Evaluation of the toxicity of zinc in the rat olfactory neuronal cell line, Odora.
abstract: Zinc (Zn) has long been touted as a panacea for common cold. Recently, there has been some controversy over whether an intranasal (IN) zinc gluconate gel, purported to fight colds, causes anosmia, or loss of the sense of smell, in humans. Previous evidence has shown that IN zinc sulfate (ZnSO4) solutions can cause anosmia in humans as well as significant damage to the olfactory epithelium in rodents. Using an in vitro olfactory neuron model (the rat Odora cell line), we tested the hypothesis that Zn toxicity was caused by inhibition of the hydrogen voltage-gated channel 1(HVCN1), leading to acidosis and apoptotic cell death. Following studies to characterize the toxicity of zinc gluconate and ZnSO4, Odora cells were grown on coverslips and loaded with 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein acetoxymethyl ester to measure intracellular pH in the presence and absence of Zn salts. While we found that HVCN1 is not functional in Odora cells, we found that olfactory neurons in vitro maintain their intracellular pH through a sodium/proton exchanger, specifically the sodium proton antiporter 1. ZnSO4, at nontoxic levels, had no impact on intracellular pH after acute exposure or after 24 h of incubation with the cells. In conclusion, Zn toxicity is not mediated through an acidification of intracellular pH in olfactory neurons in vitro.
authors: Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors: H
authors: H
authors: Hsieh
authors: Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors: H
authors: H
authors: Amlal
authors: Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH, USA marybeth.genter@uc.edu.
authors: M B
authors: MB
authors: Genter
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005942:Gluconates / Q000633:toxicity*; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000235:genetics; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009831:Olfactory Mucosa / Q000166:cytology; D051381:Rats; D015032:Zinc / Q000633:toxicity*; D019287:Zinc Sulfate / Q000633:toxicity*
chemical_list: D005942:Gluconates; C000592391:Hv1 proton channel, rat; D007473:Ion Channels; D019287:Zinc Sulfate; D015032:Zinc; C030691:gluconic acid
keywords: Odora cells; Zinc; anosmia; intracellular pH; olfactory; toxicity