Toxicity of Silver Nanoparticles and Induced Cytokine Expression with Special Reference to the Rat Cochlea

Event start date
Event start time
12.00
Place

Finn-Medi 5, auditorium, address: Biokatu 12.

Organiser(s)

Doctoral defence of MD Hao Feng

Toxicity of Silver Nanoparticles and Induced Cytokine Expression with Special Reference to the Rat Cochlea

The field of science of the dissertation is Otorhinolaryngology.

The opponent is professor Jussi Jero (University of Helsinki). Professor Emeritus Ilmari Pyykkö acts as the custos.

The language of the dissertation defence is English.

Toxicity of Silver Nanoparticles and Induced Cytokine Expression with Special Reference to the Rat Cochlea

Silver nanoparticles (Ag NPs) are one of the most prevalent metal nanoparticles. They display potent anti-bacterial, anti-viral, and anti-fungal activities and are reportedly efficient in treating otitis media. However, increasing applications of Ag NPs have raised concerns as to their potential adverse effects on human health. In particular, possible toxicological mechanism in the cochlea is not well documented.

Currently, various methods are used to evaluate the toxicity of Ag NPs. However, they are quite complicated and vary from case to case when applied. Recently, alternative methods (e.g., tissue equivalents) have been accepted in the in vivo study for regulatory purpose in Europe. Therefore, the European Union 7th framework programme large-scale integrating project NanoValid is launched and attempts to establish the new reference methods in nanotoxicology (http://www.nanovalid.eu/).

Previous studies from our group showed that the rat ear was as an excellent multifunctional model in pharmacological and toxicological research due to its unique and sophisticated structure that houses epithelia (e.g., the skin of the external ear canal and mucosa of the middle ear), sensory organs (e.g., Corti’s organ, crista ampullaris, saccule maculae, and utricle maculae), neurons of the cranial nerves (e.g., spiral ganglion and Scarpa’s ganglion), a vascular bed similar to the brain, and a biological barrier (the blood-inner ear barrier) that limit the entry of hazardous substances to avoid compromising the vulnerable homeostasis of the inner ear. Therefore, it is assumed that not only can the impact on the skin of the external ear canal and mucosa of the middle ear be shown but also potential hazardous effects on the sensory organs can be evaluated using gadolinium-enhanced MRI with high accuracy and sensitivity when Ag NPs cross the biological barriers and enter the inner ear. In addition, possible effects on hearing caused by Ag NPs can be studied by ABR measurements, and possible alterations in cytokine expression in the inner ear exposed to Ag NPs can be identified by immunostaining using confocal microscopy.

The current study aimed to evaluate the toxicity of Ag NPs by comparing its effects on BALB/c 3T3 and rat cochlear cells. Moreover, the transportation and distribution of Ag NPs in the rat ear after transtympanic injection was demonstrated using micro CT and the impact of Ag NPs on the permeability of biological barriers in the rat ear was shown using gadolinium-enhanced MRI. Finally, the molecular mechanism of Ag NPs-induced functional change in the biological barriers in the rat cochlea was elucidated using immunohistochemistry.

The outlined results suggest that the delivery concentration of Ag NPs in possible future clinical application should be tightly controlled. The rat ear model might be expanded to study other engineered nanomaterials in nanotoxicology research.
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The dissertation is published in the publication series of Acta Universitatis Tamperensis; 2210, Tampere University Press, Tampere 2016. ISBN 978-952-03-0227-6, ISSN 1455-1616. The dissertation is also published in the e-series Acta Electronica Universitatis Tamperensis; 1710, Tampere University Press 2016. ISBN 978-952-03-0228-3, ISSN 1456-954X.

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