Cargando…

Neuroprotective Effect of Ramipril Is Mediated by AT2 in a Mouse MODEL of Paclitaxel-Induced Peripheral Neuropathy

Paclitaxel (PTX)-induced peripheral neuropathy (PIPN) induces numerous symptoms affecting patient quality of life, leading to decreased doses or even to cessation of anticancer therapy. Previous studies have reported that a widely used drug, ramipril, improves neuroprotection in several rodent model...

Descripción completa

Detalles Bibliográficos
Autores principales: Bouchenaki, Hichem, Bernard, Amandine, Bessaguet, Flavien, Frachet, Simon, Richard, Laurence, Sturtz, Franck, Magy, Laurent, Bourthoumieu, Sylvie, Demiot, Claire, Danigo, Aurore
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9030366/
https://www.ncbi.nlm.nih.gov/pubmed/35456682
http://dx.doi.org/10.3390/pharmaceutics14040848
_version_ 1784692121323700224
author Bouchenaki, Hichem
Bernard, Amandine
Bessaguet, Flavien
Frachet, Simon
Richard, Laurence
Sturtz, Franck
Magy, Laurent
Bourthoumieu, Sylvie
Demiot, Claire
Danigo, Aurore
author_facet Bouchenaki, Hichem
Bernard, Amandine
Bessaguet, Flavien
Frachet, Simon
Richard, Laurence
Sturtz, Franck
Magy, Laurent
Bourthoumieu, Sylvie
Demiot, Claire
Danigo, Aurore
author_sort Bouchenaki, Hichem
collection PubMed
description Paclitaxel (PTX)-induced peripheral neuropathy (PIPN) induces numerous symptoms affecting patient quality of life, leading to decreased doses or even to cessation of anticancer therapy. Previous studies have reported that a widely used drug, ramipril, improves neuroprotection in several rodent models of peripheral neuropathy. The protective role of the angiotensin II type 2 receptor (AT2) in the central and peripheral nervous systems is well-established. Here, we evaluate the effects of ramipril in the prevention of PIPN and the involvement of AT2 in this effect. Paclitaxel was administered in wild type or AT2-deficient mice on alternate days for 8 days, at a cumulative dose of 8 mg/kg (2 mg/kg per injection). Ramipril, PD123319 (an AT2 antagonist), or a combination of both were administered one day before PTX administration, and daily for the next twenty days. PTX-administered mice developed mechanical allodynia and showed a loss of sensory nerve fibers. Ramipril prevented the functional and morphological alterations in PTX mice. The preventive effect of ramipril against tactile allodynia was completely absent in AT2-deficient mice and was counteracted by PD123319 administration in wild type mice. Our work highlights the potential of ramipril as a novel preventive treatment for PIPN, and points to the involvement of AT2 in the neuroprotective role of ramipril in PIPN.
format Online
Article
Text
id pubmed-9030366
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-90303662022-04-23 Neuroprotective Effect of Ramipril Is Mediated by AT2 in a Mouse MODEL of Paclitaxel-Induced Peripheral Neuropathy Bouchenaki, Hichem Bernard, Amandine Bessaguet, Flavien Frachet, Simon Richard, Laurence Sturtz, Franck Magy, Laurent Bourthoumieu, Sylvie Demiot, Claire Danigo, Aurore Pharmaceutics Article Paclitaxel (PTX)-induced peripheral neuropathy (PIPN) induces numerous symptoms affecting patient quality of life, leading to decreased doses or even to cessation of anticancer therapy. Previous studies have reported that a widely used drug, ramipril, improves neuroprotection in several rodent models of peripheral neuropathy. The protective role of the angiotensin II type 2 receptor (AT2) in the central and peripheral nervous systems is well-established. Here, we evaluate the effects of ramipril in the prevention of PIPN and the involvement of AT2 in this effect. Paclitaxel was administered in wild type or AT2-deficient mice on alternate days for 8 days, at a cumulative dose of 8 mg/kg (2 mg/kg per injection). Ramipril, PD123319 (an AT2 antagonist), or a combination of both were administered one day before PTX administration, and daily for the next twenty days. PTX-administered mice developed mechanical allodynia and showed a loss of sensory nerve fibers. Ramipril prevented the functional and morphological alterations in PTX mice. The preventive effect of ramipril against tactile allodynia was completely absent in AT2-deficient mice and was counteracted by PD123319 administration in wild type mice. Our work highlights the potential of ramipril as a novel preventive treatment for PIPN, and points to the involvement of AT2 in the neuroprotective role of ramipril in PIPN. MDPI 2022-04-12 /pmc/articles/PMC9030366/ /pubmed/35456682 http://dx.doi.org/10.3390/pharmaceutics14040848 Text en © 2022 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
Bouchenaki, Hichem
Bernard, Amandine
Bessaguet, Flavien
Frachet, Simon
Richard, Laurence
Sturtz, Franck
Magy, Laurent
Bourthoumieu, Sylvie
Demiot, Claire
Danigo, Aurore
Neuroprotective Effect of Ramipril Is Mediated by AT2 in a Mouse MODEL of Paclitaxel-Induced Peripheral Neuropathy
title Neuroprotective Effect of Ramipril Is Mediated by AT2 in a Mouse MODEL of Paclitaxel-Induced Peripheral Neuropathy
title_full Neuroprotective Effect of Ramipril Is Mediated by AT2 in a Mouse MODEL of Paclitaxel-Induced Peripheral Neuropathy
title_fullStr Neuroprotective Effect of Ramipril Is Mediated by AT2 in a Mouse MODEL of Paclitaxel-Induced Peripheral Neuropathy
title_full_unstemmed Neuroprotective Effect of Ramipril Is Mediated by AT2 in a Mouse MODEL of Paclitaxel-Induced Peripheral Neuropathy
title_short Neuroprotective Effect of Ramipril Is Mediated by AT2 in a Mouse MODEL of Paclitaxel-Induced Peripheral Neuropathy
title_sort neuroprotective effect of ramipril is mediated by at2 in a mouse model of paclitaxel-induced peripheral neuropathy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9030366/
https://www.ncbi.nlm.nih.gov/pubmed/35456682
http://dx.doi.org/10.3390/pharmaceutics14040848
work_keys_str_mv AT bouchenakihichem neuroprotectiveeffectoframiprilismediatedbyat2inamousemodelofpaclitaxelinducedperipheralneuropathy
AT bernardamandine neuroprotectiveeffectoframiprilismediatedbyat2inamousemodelofpaclitaxelinducedperipheralneuropathy
AT bessaguetflavien neuroprotectiveeffectoframiprilismediatedbyat2inamousemodelofpaclitaxelinducedperipheralneuropathy
AT frachetsimon neuroprotectiveeffectoframiprilismediatedbyat2inamousemodelofpaclitaxelinducedperipheralneuropathy
AT richardlaurence neuroprotectiveeffectoframiprilismediatedbyat2inamousemodelofpaclitaxelinducedperipheralneuropathy
AT sturtzfranck neuroprotectiveeffectoframiprilismediatedbyat2inamousemodelofpaclitaxelinducedperipheralneuropathy
AT magylaurent neuroprotectiveeffectoframiprilismediatedbyat2inamousemodelofpaclitaxelinducedperipheralneuropathy
AT bourthoumieusylvie neuroprotectiveeffectoframiprilismediatedbyat2inamousemodelofpaclitaxelinducedperipheralneuropathy
AT demiotclaire neuroprotectiveeffectoframiprilismediatedbyat2inamousemodelofpaclitaxelinducedperipheralneuropathy
AT danigoaurore neuroprotectiveeffectoframiprilismediatedbyat2inamousemodelofpaclitaxelinducedperipheralneuropathy