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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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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 |
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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 |
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