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Effects of Androgen Receptor Inhibition on Kanamycin-Induced Hearing Loss in Rats

Megalin has been proposed as an endocytic receptor for aminoglycosides as well as estrogen and androgen. We aimed to investigate the otoprotective effects of antiandrogens (flutamide, FM) on kanamycin (KM)-induced hearing loss in rats. Rats were divided into four groups. The KM group was administere...

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Autores principales: Chun, Kyung-Ju, Lee, Chang-Ho, Kim, Kyung-Woon, Lee, So-Min, Kim, So-Young
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158097/
https://www.ncbi.nlm.nih.gov/pubmed/34070066
http://dx.doi.org/10.3390/ijms22105307
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author Chun, Kyung-Ju
Lee, Chang-Ho
Kim, Kyung-Woon
Lee, So-Min
Kim, So-Young
author_facet Chun, Kyung-Ju
Lee, Chang-Ho
Kim, Kyung-Woon
Lee, So-Min
Kim, So-Young
author_sort Chun, Kyung-Ju
collection PubMed
description Megalin has been proposed as an endocytic receptor for aminoglycosides as well as estrogen and androgen. We aimed to investigate the otoprotective effects of antiandrogens (flutamide, FM) on kanamycin (KM)-induced hearing loss in rats. Rats were divided into four groups. The KM group was administered KM (20 mg/kg/day) for 5 days, while the FM group received FM (15 mg/kg/day) for 10 days. In the KM + FM group, KM and FM (15 mg/kg/day) were simultaneously injected for 5 days and then FM was injected for 5 days. Auditory brainstem responses were measured. Western blotting and/or quantitative reverse transcriptase-polymerase chain reaction were performed for megalin, cytochrome P450 1A1 (Cyp1a1), Cyp1b1, metallothionein 1A (MT1A), MT2A, tumor necrosis factor (TNF)-α, caspase 3, and cleaved caspase 3. The FM + KM group showed attenuated auditory thresholds when compared with the KM group at 4, 8, 16, and 32 kHz (all p < 0.05). The KM + FM group showed lower megalin and Cyp1b1 levels than the KM group (all p < 0.05). The KM + FM group revealed lower MT1A, TNFα, and caspase 3 protein levels, compared with those in the KM group (all p < 0.05). Androgen receptor inhibition protects against cochlear injuries in KM-induced hearing loss rats by attenuating megalin expression, revealing anti-inflammatory and anti-apoptotic effects.
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spelling pubmed-81580972021-05-28 Effects of Androgen Receptor Inhibition on Kanamycin-Induced Hearing Loss in Rats Chun, Kyung-Ju Lee, Chang-Ho Kim, Kyung-Woon Lee, So-Min Kim, So-Young Int J Mol Sci Article Megalin has been proposed as an endocytic receptor for aminoglycosides as well as estrogen and androgen. We aimed to investigate the otoprotective effects of antiandrogens (flutamide, FM) on kanamycin (KM)-induced hearing loss in rats. Rats were divided into four groups. The KM group was administered KM (20 mg/kg/day) for 5 days, while the FM group received FM (15 mg/kg/day) for 10 days. In the KM + FM group, KM and FM (15 mg/kg/day) were simultaneously injected for 5 days and then FM was injected for 5 days. Auditory brainstem responses were measured. Western blotting and/or quantitative reverse transcriptase-polymerase chain reaction were performed for megalin, cytochrome P450 1A1 (Cyp1a1), Cyp1b1, metallothionein 1A (MT1A), MT2A, tumor necrosis factor (TNF)-α, caspase 3, and cleaved caspase 3. The FM + KM group showed attenuated auditory thresholds when compared with the KM group at 4, 8, 16, and 32 kHz (all p < 0.05). The KM + FM group showed lower megalin and Cyp1b1 levels than the KM group (all p < 0.05). The KM + FM group revealed lower MT1A, TNFα, and caspase 3 protein levels, compared with those in the KM group (all p < 0.05). Androgen receptor inhibition protects against cochlear injuries in KM-induced hearing loss rats by attenuating megalin expression, revealing anti-inflammatory and anti-apoptotic effects. MDPI 2021-05-18 /pmc/articles/PMC8158097/ /pubmed/34070066 http://dx.doi.org/10.3390/ijms22105307 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chun, Kyung-Ju
Lee, Chang-Ho
Kim, Kyung-Woon
Lee, So-Min
Kim, So-Young
Effects of Androgen Receptor Inhibition on Kanamycin-Induced Hearing Loss in Rats
title Effects of Androgen Receptor Inhibition on Kanamycin-Induced Hearing Loss in Rats
title_full Effects of Androgen Receptor Inhibition on Kanamycin-Induced Hearing Loss in Rats
title_fullStr Effects of Androgen Receptor Inhibition on Kanamycin-Induced Hearing Loss in Rats
title_full_unstemmed Effects of Androgen Receptor Inhibition on Kanamycin-Induced Hearing Loss in Rats
title_short Effects of Androgen Receptor Inhibition on Kanamycin-Induced Hearing Loss in Rats
title_sort effects of androgen receptor inhibition on kanamycin-induced hearing loss in rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158097/
https://www.ncbi.nlm.nih.gov/pubmed/34070066
http://dx.doi.org/10.3390/ijms22105307
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