Ups and Downs of Viagra: Revisiting Ototoxicity in the Mouse Model

Sildenafil citrate (Viagra), a phosphodiesterase 5 inhibitor (PDE5i), is a commonly prescribed drug for erectile dysfunction. Since the introduction of Viagra in 1997, several case reports have linked Viagra to sudden sensorineural hearing loss. However, these studies are not well controlled for con...

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Autores principales: Au, Adrian, Stuyt, John Gerka, Chen, Daniel, Alagramam, Kumar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3828335/
https://www.ncbi.nlm.nih.gov/pubmed/24244454
http://dx.doi.org/10.1371/journal.pone.0079226
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author Au, Adrian
Stuyt, John Gerka
Chen, Daniel
Alagramam, Kumar
author_facet Au, Adrian
Stuyt, John Gerka
Chen, Daniel
Alagramam, Kumar
author_sort Au, Adrian
collection PubMed
description Sildenafil citrate (Viagra), a phosphodiesterase 5 inhibitor (PDE5i), is a commonly prescribed drug for erectile dysfunction. Since the introduction of Viagra in 1997, several case reports have linked Viagra to sudden sensorineural hearing loss. However, these studies are not well controlled for confounding factors, such as age and noise-induced hearing loss and none of these reports are based on prospective double-blind studies. Further, animal studies report contradictory data. For example, one study (2008) reported hearing loss in rats after long-term and high-dose exposure to sildenafil citrate. The other study (2012) showed vardenafil, another formulation of PDE5i, to be protective against noise-induced hearing loss in mice and rats. Whether or not clinically relevant doses of sildenafil citrate cause hearing loss in normal subjects (animals or humans) is controversial. One possibility is that PDE5i exacerbates age-related susceptibility to hearing loss in adults. Therefore, we tested sildenafil citrate in C57BL/6J, a strain of mice that displays increased susceptibility to age-related hearing loss, and compared the results to those obtained from the FVB/N, a strain of mice with no predisposition to hearing loss. Six-week-old mice were injected with the maximum tolerated dose of sildenafil citrate (10 mg/kg/day) or saline for 30 days. Auditory brainstem responses (ABRs) were recorded pre- and post injection time points to assess hearing loss. Entry of sildenafil citrate in the mouse cochlea was confirmed by qRT-PCR analysis of a downstream target of the cGMP-PKG cascade. ABR data indicated no statistically significant difference in hearing between treated and untreated mice in both backgrounds. Results show that the maximum tolerated dose of sildenafil citrate administered daily for 4 weeks does not affect hearing in the mouse. Our study gives no indication that Viagra will negatively impact hearing and it emphasizes the need to revisit the issue of Viagra related ototoxicity in humans.
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spelling pubmed-38283352013-11-16 Ups and Downs of Viagra: Revisiting Ototoxicity in the Mouse Model Au, Adrian Stuyt, John Gerka Chen, Daniel Alagramam, Kumar PLoS One Research Article Sildenafil citrate (Viagra), a phosphodiesterase 5 inhibitor (PDE5i), is a commonly prescribed drug for erectile dysfunction. Since the introduction of Viagra in 1997, several case reports have linked Viagra to sudden sensorineural hearing loss. However, these studies are not well controlled for confounding factors, such as age and noise-induced hearing loss and none of these reports are based on prospective double-blind studies. Further, animal studies report contradictory data. For example, one study (2008) reported hearing loss in rats after long-term and high-dose exposure to sildenafil citrate. The other study (2012) showed vardenafil, another formulation of PDE5i, to be protective against noise-induced hearing loss in mice and rats. Whether or not clinically relevant doses of sildenafil citrate cause hearing loss in normal subjects (animals or humans) is controversial. One possibility is that PDE5i exacerbates age-related susceptibility to hearing loss in adults. Therefore, we tested sildenafil citrate in C57BL/6J, a strain of mice that displays increased susceptibility to age-related hearing loss, and compared the results to those obtained from the FVB/N, a strain of mice with no predisposition to hearing loss. Six-week-old mice were injected with the maximum tolerated dose of sildenafil citrate (10 mg/kg/day) or saline for 30 days. Auditory brainstem responses (ABRs) were recorded pre- and post injection time points to assess hearing loss. Entry of sildenafil citrate in the mouse cochlea was confirmed by qRT-PCR analysis of a downstream target of the cGMP-PKG cascade. ABR data indicated no statistically significant difference in hearing between treated and untreated mice in both backgrounds. Results show that the maximum tolerated dose of sildenafil citrate administered daily for 4 weeks does not affect hearing in the mouse. Our study gives no indication that Viagra will negatively impact hearing and it emphasizes the need to revisit the issue of Viagra related ototoxicity in humans. Public Library of Science 2013-11-14 /pmc/articles/PMC3828335/ /pubmed/24244454 http://dx.doi.org/10.1371/journal.pone.0079226 Text en © 2013 Au et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Au, Adrian
Stuyt, John Gerka
Chen, Daniel
Alagramam, Kumar
Ups and Downs of Viagra: Revisiting Ototoxicity in the Mouse Model
title Ups and Downs of Viagra: Revisiting Ototoxicity in the Mouse Model
title_full Ups and Downs of Viagra: Revisiting Ototoxicity in the Mouse Model
title_fullStr Ups and Downs of Viagra: Revisiting Ototoxicity in the Mouse Model
title_full_unstemmed Ups and Downs of Viagra: Revisiting Ototoxicity in the Mouse Model
title_short Ups and Downs of Viagra: Revisiting Ototoxicity in the Mouse Model
title_sort ups and downs of viagra: revisiting ototoxicity in the mouse model
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3828335/
https://www.ncbi.nlm.nih.gov/pubmed/24244454
http://dx.doi.org/10.1371/journal.pone.0079226
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