Aminophylline restores glucocorticoid sensitivity in a guinea pig model of sudden sensorineural hearing loss induced by lipopolysaccharide

Abstract Glucocorticoids have been used to treat hearing loss and vestibular dysfunction for many years. However, some reports have indicated that a subset of patients with these disorders exhibit glucocorticoid insensitivity or resistance. A reduction in histone deacetylase 2 (HDAC2) activity and e...

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Autores principales:	Qiong-Qiong Zhou, Yan-Hong Dai, Xiao-Ping Du, Jie Hou, Hui Qi, Wan-Dong She
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/774506c42aa24446889c3de94d04c724
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spelling	oai:doaj.org-article:774506c42aa24446889c3de94d04c7242021-12-02T11:40:44ZAminophylline restores glucocorticoid sensitivity in a guinea pig model of sudden sensorineural hearing loss induced by lipopolysaccharide10.1038/s41598-017-02956-x2045-2322https://doaj.org/article/774506c42aa24446889c3de94d04c7242017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02956-xhttps://doaj.org/toc/2045-2322Abstract Glucocorticoids have been used to treat hearing loss and vestibular dysfunction for many years. However, some reports have indicated that a subset of patients with these disorders exhibit glucocorticoid insensitivity or resistance. A reduction in histone deacetylase 2 (HDAC2) activity and expression has been reported to play a critical role in glucocorticoid resistance. Here, we investigated the protective effects of aminophylline on HDAC2 expression and glucocorticoid sensitivity in lipopolysaccharide (LPS)-induced sudden sensorineural hearing loss in guinea pigs. We assessed hearing recovery in LPS-applied guinea pigs, which were either left untreated or were systemically treated with either dexamethasone, aminophylline, or a combination of the two. We utilized fluorescence microscopy and enzyme-linked immunosorbent assay to analyze the distribution patterns of HDAC2 and detect its levels in the cochlea. We used hematoxylin-eosin staining to examine cochlear histopathological changes. In the absence of treatment, significant hearing loss was detected in LPS-exposed animals. A synergistic effect was observed between aminophylline and dexamethasone in maintaining HDAC2 expression levels, preventing hearing loss in LPS-exposed animals and reducing cochlear damage. This study indicates that aminophylline can restore glucocorticoid sensitivity, which provides a new approach to treating patients with hearing disorders who are refractory to glucocorticoids.Qiong-Qiong ZhouYan-Hong DaiXiao-Ping DuJie HouHui QiWan-Dong SheNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Qiong-Qiong Zhou Yan-Hong Dai Xiao-Ping Du Jie Hou Hui Qi Wan-Dong She Aminophylline restores glucocorticoid sensitivity in a guinea pig model of sudden sensorineural hearing loss induced by lipopolysaccharide
description	Abstract Glucocorticoids have been used to treat hearing loss and vestibular dysfunction for many years. However, some reports have indicated that a subset of patients with these disorders exhibit glucocorticoid insensitivity or resistance. A reduction in histone deacetylase 2 (HDAC2) activity and expression has been reported to play a critical role in glucocorticoid resistance. Here, we investigated the protective effects of aminophylline on HDAC2 expression and glucocorticoid sensitivity in lipopolysaccharide (LPS)-induced sudden sensorineural hearing loss in guinea pigs. We assessed hearing recovery in LPS-applied guinea pigs, which were either left untreated or were systemically treated with either dexamethasone, aminophylline, or a combination of the two. We utilized fluorescence microscopy and enzyme-linked immunosorbent assay to analyze the distribution patterns of HDAC2 and detect its levels in the cochlea. We used hematoxylin-eosin staining to examine cochlear histopathological changes. In the absence of treatment, significant hearing loss was detected in LPS-exposed animals. A synergistic effect was observed between aminophylline and dexamethasone in maintaining HDAC2 expression levels, preventing hearing loss in LPS-exposed animals and reducing cochlear damage. This study indicates that aminophylline can restore glucocorticoid sensitivity, which provides a new approach to treating patients with hearing disorders who are refractory to glucocorticoids.
format	article
author	Qiong-Qiong Zhou Yan-Hong Dai Xiao-Ping Du Jie Hou Hui Qi Wan-Dong She
author_facet	Qiong-Qiong Zhou Yan-Hong Dai Xiao-Ping Du Jie Hou Hui Qi Wan-Dong She
author_sort	Qiong-Qiong Zhou
title	Aminophylline restores glucocorticoid sensitivity in a guinea pig model of sudden sensorineural hearing loss induced by lipopolysaccharide
title_short	Aminophylline restores glucocorticoid sensitivity in a guinea pig model of sudden sensorineural hearing loss induced by lipopolysaccharide
title_full	Aminophylline restores glucocorticoid sensitivity in a guinea pig model of sudden sensorineural hearing loss induced by lipopolysaccharide
title_fullStr	Aminophylline restores glucocorticoid sensitivity in a guinea pig model of sudden sensorineural hearing loss induced by lipopolysaccharide
title_full_unstemmed	Aminophylline restores glucocorticoid sensitivity in a guinea pig model of sudden sensorineural hearing loss induced by lipopolysaccharide
title_sort	aminophylline restores glucocorticoid sensitivity in a guinea pig model of sudden sensorineural hearing loss induced by lipopolysaccharide
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/774506c42aa24446889c3de94d04c724
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Aminophylline restores glucocorticoid sensitivity in a guinea pig model of sudden sensorineural hearing loss induced by lipopolysaccharide

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