Franco-Vidal Valérie, Beurg Maryline, Darrouzet Vincent, Bébéar Jean-Pierre, Skinner Liam J, Dulon Didier
Otolaryngology and Skull Base Surgery Department, University of Bordeaux 2 Victor Segalen, Bordeaux, France.
Audiol Neurootol. 2008;13(1):65-70. doi: 10.1159/000108763. Epub 2007 Sep 21.
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.
肺炎链球菌可引发局部和全身性疾病，如脑膜炎、中耳炎和肺炎。这些脑膜炎病例中有三分之一可能与不可逆的感音神经性听力损失有关，其机制可能涉及外毒素肺炎溶血素（PLY），它会不可逆地损害耳蜗毛细胞（HCs）。在呼吸系统和神经元中，已经证明锌缺乏会增加动物模型和儿童此类感染的严重程度和死亡率。此外，补充锌可以降低肺炎球菌呼吸道感染的严重程度。我们研究的目的是评估锌对培养的毛细胞中PLY毒性的潜在保护作用。我们的结果表明，在低至1 microM的锌存在下，PLY对内外毛细胞的毒性大幅降低了约50%。在300 microM的锌浓度下，内毛细胞和外毛细胞的保护作用分别显著增加至62%和55.2%。我们的结果表明，锌的保护作用可能是由于抑制了毒素掺入和聚集到质膜中，从而防止钙通过毒素孔流入。我们的研究结果提出了用锌进行治疗可能有助于预防肺炎球菌感染导致的使人衰弱的耳科后遗症的可能性。
