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In silico pharmacological study of AQP2 inhibition by steroids contextualized to Ménière’s disease treatments

Ménière’s disease (MD) is characterized by an abnormal dilatation of the endolymphatic compartment called endolymphatic hydrops and is associated with fluctuating hearing losses and vertigo. Corticosteroid treatment is typically administered for its anti-inflammatory effects to MD patients. However,...

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Autores principales: Mom, Robin, Réty, Stéphane, Mocquet, Vincent, Auguin, Daniel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10620702/
https://www.ncbi.nlm.nih.gov/pubmed/37928160
http://dx.doi.org/10.3389/fneur.2023.1270092
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author Mom, Robin
Réty, Stéphane
Mocquet, Vincent
Auguin, Daniel
author_facet Mom, Robin
Réty, Stéphane
Mocquet, Vincent
Auguin, Daniel
author_sort Mom, Robin
collection PubMed
description Ménière’s disease (MD) is characterized by an abnormal dilatation of the endolymphatic compartment called endolymphatic hydrops and is associated with fluctuating hearing losses and vertigo. Corticosteroid treatment is typically administered for its anti-inflammatory effects to MD patients. However, we recently described for the first time a direct interaction of two corticosteroids (dexamethasone and cortisol) with human AQP2 which strongly inhibited water fluxes. From these initial studies, we proposed an AQPs Corticosteroids Binding Site (ACBS). In the present work, we tested the interaction of 10 molecules associated to the steroid family for this putative ACBS. We observed a wide diversity of affinity and inhibitory potential of these molecules toward AQP2 and discussed the implications for inner ear physiology. Among the tested compounds, cholecalciferol, calcitriol and oestradiol were the most efficient AQP2 water permeability inhibitors.
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spelling pubmed-106207022023-11-03 In silico pharmacological study of AQP2 inhibition by steroids contextualized to Ménière’s disease treatments Mom, Robin Réty, Stéphane Mocquet, Vincent Auguin, Daniel Front Neurol Neurology Ménière’s disease (MD) is characterized by an abnormal dilatation of the endolymphatic compartment called endolymphatic hydrops and is associated with fluctuating hearing losses and vertigo. Corticosteroid treatment is typically administered for its anti-inflammatory effects to MD patients. However, we recently described for the first time a direct interaction of two corticosteroids (dexamethasone and cortisol) with human AQP2 which strongly inhibited water fluxes. From these initial studies, we proposed an AQPs Corticosteroids Binding Site (ACBS). In the present work, we tested the interaction of 10 molecules associated to the steroid family for this putative ACBS. We observed a wide diversity of affinity and inhibitory potential of these molecules toward AQP2 and discussed the implications for inner ear physiology. Among the tested compounds, cholecalciferol, calcitriol and oestradiol were the most efficient AQP2 water permeability inhibitors. Frontiers Media S.A. 2023-10-19 /pmc/articles/PMC10620702/ /pubmed/37928160 http://dx.doi.org/10.3389/fneur.2023.1270092 Text en Copyright © 2023 Mom, Réty, Mocquet and Auguin. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neurology
Mom, Robin
Réty, Stéphane
Mocquet, Vincent
Auguin, Daniel
In silico pharmacological study of AQP2 inhibition by steroids contextualized to Ménière’s disease treatments
title In silico pharmacological study of AQP2 inhibition by steroids contextualized to Ménière’s disease treatments
title_full In silico pharmacological study of AQP2 inhibition by steroids contextualized to Ménière’s disease treatments
title_fullStr In silico pharmacological study of AQP2 inhibition by steroids contextualized to Ménière’s disease treatments
title_full_unstemmed In silico pharmacological study of AQP2 inhibition by steroids contextualized to Ménière’s disease treatments
title_short In silico pharmacological study of AQP2 inhibition by steroids contextualized to Ménière’s disease treatments
title_sort in silico pharmacological study of aqp2 inhibition by steroids contextualized to ménière’s disease treatments
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10620702/
https://www.ncbi.nlm.nih.gov/pubmed/37928160
http://dx.doi.org/10.3389/fneur.2023.1270092
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