Calmangafodipir Reduces Sensory Alterations and Prevents Intraepidermal Nerve Fibers Loss in a Mouse Model of Oxaliplatin Induced Peripheral Neurotoxicity
Oxaliplatin (OHP) is an antineoplastic compound able to induce peripheral neurotoxicity. Oxidative stress has been suggested to be a key factor in the development of OHP-related peripheral neurotoxicity. Mangafodipir, a contrast agent possessing mitochondrial superoxide dismutase (MnSOD)-mimetic act...
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MDPI AG
2020-07-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/9/7/594 |
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| author | Annalisa Canta Alessia Chiorazzi Eleonora Pozzi Giulia Fumagalli Laura Monza Cristina Meregalli Valentina A. Carozzi Virginia Rodriguez-Menendez Norberto Oggioni Jacques Näsström Paola Marmiroli Guido Cavaletti |
| author_facet | Annalisa Canta Alessia Chiorazzi Eleonora Pozzi Giulia Fumagalli Laura Monza Cristina Meregalli Valentina A. Carozzi Virginia Rodriguez-Menendez Norberto Oggioni Jacques Näsström Paola Marmiroli Guido Cavaletti |
| author_sort | Annalisa Canta |
| collection | DOAJ |
| description | Oxaliplatin (OHP) is an antineoplastic compound able to induce peripheral neurotoxicity. Oxidative stress has been suggested to be a key factor in the development of OHP-related peripheral neurotoxicity. Mangafodipir, a contrast agent possessing mitochondrial superoxide dismutase (MnSOD)-mimetic activity, has been tested as a cytoprotector in chemotherapy-induced peripheral neurotoxicity (CIPN). Calmangafodipir (PledOx<sup>®</sup>) has even better therapeutic activity. We investigated a BALB/c mouse model of OHP-related CIPN and the effects of the pre-treatment of calmangafodipir (2.5, 5, or 10 mg/kg intravenously) on sensory perception, and we performed a pathological study on skin biopsies to assess intraepidermal nerve fiber (IENF) density. At the end of the treatments, OHP alone or in pre-treatment with calmangafodipir 2.5 and 10 mg/kg, induced mechanical allodynia and cold thermal hyperalgesia, but calmangafodipir 5 mg/kg prevented these effects. Accordingly, OHP alone or in pre-treatment with calmangafodipir 2.5 and 10 mg/kg, induced a significant reduction in IENF density, but calmangafodipir 5 mg/kg prevented this reduction. These results confirm a protective effect of calmangafodipir against OHP-induced small fiber neuropathy. Interestingly, these results are in agreement with previous observations suggesting a U-shaped effect of calmangafodipir, with the 10 mg/kg dose less effective than the lower doses. |
| first_indexed | 2024-03-10T18:37:30Z |
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| id | doaj.art-6ea08a32b15b46a1ba40a13deca1175c |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T18:37:30Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-6ea08a32b15b46a1ba40a13deca1175c2023-11-20T06:05:36ZengMDPI AGAntioxidants2076-39212020-07-019759410.3390/antiox9070594Calmangafodipir Reduces Sensory Alterations and Prevents Intraepidermal Nerve Fibers Loss in a Mouse Model of Oxaliplatin Induced Peripheral NeurotoxicityAnnalisa Canta0Alessia Chiorazzi1Eleonora Pozzi2Giulia Fumagalli3Laura Monza4Cristina Meregalli5Valentina A. Carozzi6Virginia Rodriguez-Menendez7Norberto Oggioni8Jacques Näsström9Paola Marmiroli10Guido Cavaletti11Experimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, Via Cadore 48, 20900 Monza, ItalyExperimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, Via Cadore 48, 20900 Monza, ItalyExperimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, Via Cadore 48, 20900 Monza, ItalyExperimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, Via Cadore 48, 20900 Monza, ItalyExperimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, Via Cadore 48, 20900 Monza, ItalyExperimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, Via Cadore 48, 20900 Monza, ItalyExperimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, Via Cadore 48, 20900 Monza, ItalyExperimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, Via Cadore 48, 20900 Monza, ItalyExperimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, Via Cadore 48, 20900 Monza, ItalyPledPharma AB, Grev Turegatan 11 C, 114 46 Stockholm, SwedenExperimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, Via Cadore 48, 20900 Monza, ItalyExperimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, Via Cadore 48, 20900 Monza, ItalyOxaliplatin (OHP) is an antineoplastic compound able to induce peripheral neurotoxicity. Oxidative stress has been suggested to be a key factor in the development of OHP-related peripheral neurotoxicity. Mangafodipir, a contrast agent possessing mitochondrial superoxide dismutase (MnSOD)-mimetic activity, has been tested as a cytoprotector in chemotherapy-induced peripheral neurotoxicity (CIPN). Calmangafodipir (PledOx<sup>®</sup>) has even better therapeutic activity. We investigated a BALB/c mouse model of OHP-related CIPN and the effects of the pre-treatment of calmangafodipir (2.5, 5, or 10 mg/kg intravenously) on sensory perception, and we performed a pathological study on skin biopsies to assess intraepidermal nerve fiber (IENF) density. At the end of the treatments, OHP alone or in pre-treatment with calmangafodipir 2.5 and 10 mg/kg, induced mechanical allodynia and cold thermal hyperalgesia, but calmangafodipir 5 mg/kg prevented these effects. Accordingly, OHP alone or in pre-treatment with calmangafodipir 2.5 and 10 mg/kg, induced a significant reduction in IENF density, but calmangafodipir 5 mg/kg prevented this reduction. These results confirm a protective effect of calmangafodipir against OHP-induced small fiber neuropathy. Interestingly, these results are in agreement with previous observations suggesting a U-shaped effect of calmangafodipir, with the 10 mg/kg dose less effective than the lower doses.https://www.mdpi.com/2076-3921/9/7/594calmangafodipiroxaliplatinIENF densitycold hyperalgesiamechanical allodynianeurotoxicity |
| spellingShingle | Annalisa Canta Alessia Chiorazzi Eleonora Pozzi Giulia Fumagalli Laura Monza Cristina Meregalli Valentina A. Carozzi Virginia Rodriguez-Menendez Norberto Oggioni Jacques Näsström Paola Marmiroli Guido Cavaletti Calmangafodipir Reduces Sensory Alterations and Prevents Intraepidermal Nerve Fibers Loss in a Mouse Model of Oxaliplatin Induced Peripheral Neurotoxicity Antioxidants calmangafodipir oxaliplatin IENF density cold hyperalgesia mechanical allodynia neurotoxicity |
| title | Calmangafodipir Reduces Sensory Alterations and Prevents Intraepidermal Nerve Fibers Loss in a Mouse Model of Oxaliplatin Induced Peripheral Neurotoxicity |
| title_full | Calmangafodipir Reduces Sensory Alterations and Prevents Intraepidermal Nerve Fibers Loss in a Mouse Model of Oxaliplatin Induced Peripheral Neurotoxicity |
| title_fullStr | Calmangafodipir Reduces Sensory Alterations and Prevents Intraepidermal Nerve Fibers Loss in a Mouse Model of Oxaliplatin Induced Peripheral Neurotoxicity |
| title_full_unstemmed | Calmangafodipir Reduces Sensory Alterations and Prevents Intraepidermal Nerve Fibers Loss in a Mouse Model of Oxaliplatin Induced Peripheral Neurotoxicity |
| title_short | Calmangafodipir Reduces Sensory Alterations and Prevents Intraepidermal Nerve Fibers Loss in a Mouse Model of Oxaliplatin Induced Peripheral Neurotoxicity |
| title_sort | calmangafodipir reduces sensory alterations and prevents intraepidermal nerve fibers loss in a mouse model of oxaliplatin induced peripheral neurotoxicity |
| topic | calmangafodipir oxaliplatin IENF density cold hyperalgesia mechanical allodynia neurotoxicity |
| url | https://www.mdpi.com/2076-3921/9/7/594 |
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