Zinc Toxicity in Odora Cells

Zinc has been touted as a panacea for the common cold. However, there has been some controversy over whether Zicam, an intranasal zinc gluconate gel purported to fight colds, causes anosmia, or the loss of the sense of smell. Historical evidence has shown that zinc sulfate solutions can cause anosmia in humans along with significant damage to the olfactory epithelium in rodents. However, more recent work has claimed to show that zinc gluconate is less toxic than zinc sulfate. Using an in vitro system to compare the toxicity of zinc sulfate and zinc gluconate on immature and mature rat olfactory sensory neurons, it was found that the toxicity of both zinc salts was similar with zinc sulfate being slightly more toxic than zinc gluconate and occurred at significantly lower concentrations than that found in Zicam nasal gel, which strengthens the epidemiological link between intranasal zinc exposure and anosmia. Mechanistic studies disproved the hypothesis that zinc toxicity was caused by inhibition of the HVCN1 proton channel which would have led to acidosis and apoptotic cell death. It was found that these immature rat olfactory sensory neurons are able to maintain their intracellular pH through a Na+/H+ exchanger, specifically NHE1, and a Cl-/HCO3- exchanger. Zinc sulfate, at non-toxic levels, had no impact on intracellular pH via proton transport either after acute exposure or after 24 hours incubation with the cells. In conclusion, zinc toxicity is not mediated through an acidification of intracellular pH.