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...
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MDPI AG
2022-04-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/4/848 |
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| author | Hichem Bouchenaki Amandine Bernard Flavien Bessaguet Simon Frachet Laurence Richard Franck Sturtz Laurent Magy Sylvie Bourthoumieu Claire Demiot Aurore Danigo |
| author_facet | Hichem Bouchenaki Amandine Bernard Flavien Bessaguet Simon Frachet Laurence Richard Franck Sturtz Laurent Magy Sylvie Bourthoumieu Claire Demiot Aurore Danigo |
| author_sort | Hichem Bouchenaki |
| collection | DOAJ |
| 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. |
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| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T10:30:32Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-da4dfbc37d634bef9db9c80ed1dbc4ea2023-12-01T21:19:00ZengMDPI AGPharmaceutics1999-49232022-04-0114484810.3390/pharmaceutics14040848Neuroprotective Effect of Ramipril Is Mediated by AT2 in a Mouse MODEL of Paclitaxel-Induced Peripheral NeuropathyHichem Bouchenaki0Amandine Bernard1Flavien Bessaguet2Simon Frachet3Laurence Richard4Franck Sturtz5Laurent Magy6Sylvie Bourthoumieu7Claire Demiot8Aurore Danigo9UR 20218-NeurIT, Faculties of Medicine and Pharmacy, University of Limoges, 87025 Limoges, FranceUR 20218-NeurIT, Faculties of Medicine and Pharmacy, University of Limoges, 87025 Limoges, FranceINSERM 1083 CNRS UMR 6015 Mitovasc Laboratory, CarMe Team, University of Angers, 49045 Angers, FranceUR 20218-NeurIT, Faculties of Medicine and Pharmacy, University of Limoges, 87025 Limoges, FranceUR 20218-NeurIT, Faculties of Medicine and Pharmacy, University of Limoges, 87025 Limoges, FranceUR 20218-NeurIT, Faculties of Medicine and Pharmacy, University of Limoges, 87025 Limoges, FranceUR 20218-NeurIT, Faculties of Medicine and Pharmacy, University of Limoges, 87025 Limoges, FranceUR 20218-NeurIT, Faculties of Medicine and Pharmacy, University of Limoges, 87025 Limoges, FranceUR 20218-NeurIT, Faculties of Medicine and Pharmacy, University of Limoges, 87025 Limoges, FranceUR 20218-NeurIT, Faculties of Medicine and Pharmacy, University of Limoges, 87025 Limoges, FrancePaclitaxel (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.https://www.mdpi.com/1999-4923/14/4/848paclitaxel-induced peripheral neuropathyangiotensin converting enzyme inhibitorRamiprilneuropathic painmouse model |
| spellingShingle | Hichem Bouchenaki Amandine Bernard Flavien Bessaguet Simon Frachet Laurence Richard Franck Sturtz Laurent Magy Sylvie Bourthoumieu Claire Demiot Aurore Danigo Neuroprotective Effect of Ramipril Is Mediated by AT2 in a Mouse MODEL of Paclitaxel-Induced Peripheral Neuropathy Pharmaceutics paclitaxel-induced peripheral neuropathy angiotensin converting enzyme inhibitor Ramipril neuropathic pain mouse model |
| 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 | paclitaxel-induced peripheral neuropathy angiotensin converting enzyme inhibitor Ramipril neuropathic pain mouse model |
| url | https://www.mdpi.com/1999-4923/14/4/848 |
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