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Zinc protection against pneumolysin toxicity on rat cochlear hair cells
Valérie Franco-Vidal1, Maryline Beurg, Vincent Darrouzet
1Otolaryngology and Skull Base Surgery Department, University of Bordeaux 2 Victor Segalen, Bordeaux, France. valerie.vidal@chu-bordeaux.fr
Abstract:
Streptococcus pneumoniae can induce local and systemic diseases such as meningitis, otitis media, and pneumonia. One third of these meningitis cases can be associated with irreversible sensorineural hearing loss whose mechanisms likely involves the exotoxin pneumolysin (PLY) that irreversibly damages cochlear hair cells (HCs). In the respiratory system and in neuron it has been demonstrated that zinc deficiency increases severity and mortality of such infections in animal models and in children. Moreover, zinc supplementation can decrease the severity of pneumococcal respiratory infections. The aim of our study was to assess the potential protective effect of zinc against PLY toxicity on HCs in culture. Our results showed that in the presence of zinc at concentration as low as 1 microM, the toxicity of PLY was largely reduced by about 50% for both inner and outer HCs. At 300 microM of zinc, protection significantly increased with 62 and 55.2% for IHCs and OHCs, respectively. Our results suggest that the protective effect of zinc is likely due to an inhibition of the toxin incorporation and aggregation into the plasma membrane, thus preventing calcium influx through the toxin pores. Our findings raise the possibility that treatments with zinc may help to prevent debilitating otological sequelae from pneumococcal infection.
Insights
Zinc supplementation may protect against pneumococcal meningitis-induced hearing loss. Zinc significantly reduced the toxic effects of pneumolysin (PLY) on cochlear hair cells in cell cultures.
Area of Science:
- Otolaryngology
- Infectious Diseases
- Toxicology
Background:
- Streptococcus pneumoniae causes meningitis, potentially leading to irreversible sensorineural hearing loss.
- Pneumolysin (PLY), an exotoxin, is implicated in damaging cochlear hair cells (HCs).
- Zinc deficiency is linked to increased infection severity; zinc supplementation may mitigate pneumococcal respiratory infections.
Purpose of the Study:
- To evaluate the protective potential of zinc against pneumolysin-induced toxicity in cultured cochlear hair cells.
Main Methods:
- Cochlear hair cells (inner and outer) were cultured.
- Toxicity of pneumolysin (PLY) was assessed in the presence of varying zinc concentrations.
- Cell viability and protection percentages were quantified.
Main Results:
- Zinc, even at 1 microM, reduced PLY toxicity by approximately 50% for both inner and outer HCs.
- At 300 microM, zinc provided significant protection: 62% for inner HCs and 55.2% for outer HCs.
- Zinc likely inhibits PLY incorporation and aggregation into the cell membrane, preventing calcium influx.
Conclusions:
- Zinc demonstrates a protective effect against pneumolysin-induced hair cell damage in vitro.
- These findings suggest zinc treatment could be a strategy to prevent hearing loss complications from pneumococcal infections.
- Further research into zinc's role in preventing otological sequelae is warranted.
