Zou Jing, Feng Hao, Mannerström Marika, Heinonen Tuula, Pyykkö Ilmari
Hearing and Balance Research Unit, Field of Oto-laryngology, School of Medicine, University of Tampere, Tampere, Finland.
Department of Otolaryngology-Head and Neck Surgery, Center for Otolaryngology-Head & Neck Surgery of Chinese PLA, Changhai Hospital, Second Military Medical University, Shanghai, China.
J Nanobiotechnology. 2014 Dec 3;12:52. doi: 10.1186/s12951-014-0052-6.
Silver nanoparticles (AgNPs) displayed strong activities in anti-bacterial, anti-viral, and anti-fungal studies and was reportedly efficient in treating otitis media .The potential impact of AgNPs on the inner ear was missing.
Attempted to evaluate the potential toxicity of AgNPs in the inner ear, middle ear, and external ear canal after transtympanic injection in rats.
In in vitro studies, the IC50 for AgNPs in neutral red uptake assay was lower than that in NAD(P)H-dependent cellular oxidoreductase enzyme assay (WST-1) and higher than that in total cellular ATP and nuclear membrane integrity (propidium iodide) assessments. In in vivo experiments, magnetic resonance imaging (MRI) showed that significant changes in the permeability of biological barriers occurred in the middle ear mucosa, the skin of the external ear canal, and the inner ear at 5 h post-transtympanic injection of AgNPs at concentrations ranging from 20 μg/ml to 4000 μg/ml. The alterations in permeability showed a dosage-response relationship, and were reversible. The auditory brainstem response showed that 4000 μg/ml AgNPs induced hearing loss with partial recovery at 7 d, whereas 20 μg/ml caused reversible hearing loss. The functional change in auditory system was in line with the histology results. In general, the BALB/c 3T3 cell line is more than 1000 times more sensitive than the in vivo studies. Impairment of the mitochondrial function was indicated to be the mechanism of toxicity of AgNPs.
These results suggest that AgNPs caused significant, dose-dependent changes in the permeability of biological barriers in the middle ear mucosa, the skin of the external ear canal, and the inner ear. In general, the BALB/c 3T3 cell line is more than 1000 times more sensitive than the in vivo studies. The rat ear model might be expended to other engineered nanomaterials in nanotoxicology study.
银纳米颗粒(AgNPs)在抗菌、抗病毒和抗真菌研究中表现出强大活性,据报道在治疗中耳炎方面有效。然而,AgNPs对内耳的潜在影响尚不清楚。
试图评估经鼓膜注射后AgNPs对大鼠内耳、中耳和外耳道的潜在毒性。
在体外研究中,中性红摄取试验中AgNPs的IC50低于NAD(P)H依赖性细胞氧化还原酶试验(WST-1),高于总细胞ATP和核膜完整性(碘化丙啶)评估。在体内实验中,磁共振成像(MRI)显示,在经鼓膜注射浓度范围为20μg/ml至4000μg/ml的AgNPs后5小时,中耳黏膜、外耳道皮肤和内耳生物屏障的通透性发生了显著变化。通透性的改变呈现剂量反应关系,且是可逆的。听性脑干反应显示,4000μg/ml的AgNPs在7天时导致听力损失并部分恢复,而20μg/ml则导致可逆性听力损失。听觉系统的功能变化与组织学结果一致。一般来说,BALB/c 3T3细胞系比体内研究敏感1000倍以上。线粒体功能受损被认为是AgNPs毒性的机制。
这些结果表明,AgNPs导致中耳黏膜、外耳道皮肤和内耳生物屏障的通透性发生显著的剂量依赖性变化。一般来说,BALB/c 3T3细胞系比体内研究敏感1000倍以上。大鼠耳模型可能会在纳米毒理学研究中扩展到其他工程纳米材料。