PEA-OXA Mitigates Oxaliplatin-Induced Painful Neuropathy through NF-κB/Nrf-2 Axis
Chemotherapy-induced neuropathy is a common, dose-dependent adverse effect of several antineoplastics, such as oxaliplatin (L-OHP). The aim of the present work was to evaluate the potential beneficial effects of 2-pentadecyl-2-oxazoline (PEA-OXA) in a murine model of oxaliplatin-induced peripheral n...
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MDPI AG
2021-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/8/3927 |
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| author | Michela Campolo Marika Lanza Irene Paterniti Alessia Filippone Alessio Ardizzone Giovanna Casili Sarah A. Scuderi Caterina Puglisi Marzia Mare Lorenzo Memeo Salvatore Cuzzocrea Emanuela Esposito |
| author_facet | Michela Campolo Marika Lanza Irene Paterniti Alessia Filippone Alessio Ardizzone Giovanna Casili Sarah A. Scuderi Caterina Puglisi Marzia Mare Lorenzo Memeo Salvatore Cuzzocrea Emanuela Esposito |
| author_sort | Michela Campolo |
| collection | DOAJ |
| description | Chemotherapy-induced neuropathy is a common, dose-dependent adverse effect of several antineoplastics, such as oxaliplatin (L-OHP). The aim of the present work was to evaluate the potential beneficial effects of 2-pentadecyl-2-oxazoline (PEA-OXA) in a murine model of oxaliplatin-induced peripheral neuropathy (OIPN). OIPN was induced by an intraperitoneally injection of L-OHP in rats on five consecutive days (D0–4) for a final cumulative dose of 10 mg/kg. PEA-OXA and ultramicronized palmitoylethanolamide (PEAum), both 10 mg/kg, were given orally 15–20 min prior (L-OHP) and sacrifice was made on day 25. Our results demonstrated that PEA-OXA, more than PEAum, reduced the development of hypersensitivity in rats; this was associated with the reduction in hyperactivation of glia cells and the increased production of proinflammatory cytokines in the dorsal horn of the spinal cord, accompanied by an upregulation of neurotrophic factors in the dorsal root ganglia (DRG). Moreover, we showed that PEA-OXA reduced L-OHP damage via a reduction in NF-κB pathway activation and a modulation of Nrf-2 pathways. Our findings identify PEA-OXA as a therapeutic target in chemotherapy-induced painful neuropathy, through the biomolecular signaling NF-κB/Nrf-2 axis, thanks to its abilities to counteract L-OHP damage. Therefore, we can consider PEA-OXA as a promising adjunct to chemotherapy to reduce chronic pain in patients. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T12:26:02Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-58f9db7b4ba24cbdb5114491f9b4dfb92023-11-21T15:02:43ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-04-01228392710.3390/ijms22083927PEA-OXA Mitigates Oxaliplatin-Induced Painful Neuropathy through NF-κB/Nrf-2 AxisMichela Campolo0Marika Lanza1Irene Paterniti2Alessia Filippone3Alessio Ardizzone4Giovanna Casili5Sarah A. Scuderi6Caterina Puglisi7Marzia Mare8Lorenzo Memeo9Salvatore Cuzzocrea10Emanuela Esposito11Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres, 98166 Messina, ItalyIOM Ricerca Srl, Via Penninazzo 11, 95029 Viagrande, ItalyIstituto Oncologico Del Mediterraneo Spa, Via Penninazzo 7, 95029 Viagrande, ItalyIstituto Oncologico Del Mediterraneo Spa, Via Penninazzo 7, 95029 Viagrande, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres, 98166 Messina, ItalyDepartment of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres, 98166 Messina, ItalyChemotherapy-induced neuropathy is a common, dose-dependent adverse effect of several antineoplastics, such as oxaliplatin (L-OHP). The aim of the present work was to evaluate the potential beneficial effects of 2-pentadecyl-2-oxazoline (PEA-OXA) in a murine model of oxaliplatin-induced peripheral neuropathy (OIPN). OIPN was induced by an intraperitoneally injection of L-OHP in rats on five consecutive days (D0–4) for a final cumulative dose of 10 mg/kg. PEA-OXA and ultramicronized palmitoylethanolamide (PEAum), both 10 mg/kg, were given orally 15–20 min prior (L-OHP) and sacrifice was made on day 25. Our results demonstrated that PEA-OXA, more than PEAum, reduced the development of hypersensitivity in rats; this was associated with the reduction in hyperactivation of glia cells and the increased production of proinflammatory cytokines in the dorsal horn of the spinal cord, accompanied by an upregulation of neurotrophic factors in the dorsal root ganglia (DRG). Moreover, we showed that PEA-OXA reduced L-OHP damage via a reduction in NF-κB pathway activation and a modulation of Nrf-2 pathways. Our findings identify PEA-OXA as a therapeutic target in chemotherapy-induced painful neuropathy, through the biomolecular signaling NF-κB/Nrf-2 axis, thanks to its abilities to counteract L-OHP damage. Therefore, we can consider PEA-OXA as a promising adjunct to chemotherapy to reduce chronic pain in patients.https://www.mdpi.com/1422-0067/22/8/3927palmitoylethanolamide ultramicronized (PEAum)2-pentadecyl-2-oxazoline (PEA-OXA)oxaliplatin (L-OHP)paindorsal root ganglia (DRG) |
| spellingShingle | Michela Campolo Marika Lanza Irene Paterniti Alessia Filippone Alessio Ardizzone Giovanna Casili Sarah A. Scuderi Caterina Puglisi Marzia Mare Lorenzo Memeo Salvatore Cuzzocrea Emanuela Esposito PEA-OXA Mitigates Oxaliplatin-Induced Painful Neuropathy through NF-κB/Nrf-2 Axis International Journal of Molecular Sciences palmitoylethanolamide ultramicronized (PEAum) 2-pentadecyl-2-oxazoline (PEA-OXA) oxaliplatin (L-OHP) pain dorsal root ganglia (DRG) |
| title | PEA-OXA Mitigates Oxaliplatin-Induced Painful Neuropathy through NF-κB/Nrf-2 Axis |
| title_full | PEA-OXA Mitigates Oxaliplatin-Induced Painful Neuropathy through NF-κB/Nrf-2 Axis |
| title_fullStr | PEA-OXA Mitigates Oxaliplatin-Induced Painful Neuropathy through NF-κB/Nrf-2 Axis |
| title_full_unstemmed | PEA-OXA Mitigates Oxaliplatin-Induced Painful Neuropathy through NF-κB/Nrf-2 Axis |
| title_short | PEA-OXA Mitigates Oxaliplatin-Induced Painful Neuropathy through NF-κB/Nrf-2 Axis |
| title_sort | pea oxa mitigates oxaliplatin induced painful neuropathy through nf κb nrf 2 axis |
| topic | palmitoylethanolamide ultramicronized (PEAum) 2-pentadecyl-2-oxazoline (PEA-OXA) oxaliplatin (L-OHP) pain dorsal root ganglia (DRG) |
| url | https://www.mdpi.com/1422-0067/22/8/3927 |
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