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Comment published on 28 August 2020, see Antioxidants 2020, 9(9), 802.
Open AccessArticle

Calmangafodipir Reduces Sensory Alterations and Prevents Intraepidermal Nerve Fibers Loss in a Mouse Model of Oxaliplatin Induced Peripheral Neurotoxicity

1
Experimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, Via Cadore 48, 20900 Monza, Italy
2
PledPharma AB, Grev Turegatan 11 C, 114 46 Stockholm, Sweden
3
Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 1, 20126 Milan, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Antioxidants 2020, 9(7), 594; https://doi.org/10.3390/antiox9070594
Received: 1 June 2020 / Revised: 26 June 2020 / Accepted: 2 July 2020 / Published: 7 July 2020
(This article belongs to the Special Issue Antioxidant and Cytoprotective Activity)
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®) 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. View Full-Text
Keywords: calmangafodipir; oxaliplatin; IENF density; cold hyperalgesia; mechanical allodynia; neurotoxicity calmangafodipir; oxaliplatin; IENF density; cold hyperalgesia; mechanical allodynia; neurotoxicity
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Canta, A.; Chiorazzi, A.; Pozzi, E.; Fumagalli, G.; Monza, L.; Meregalli, C.; Carozzi, V.A.; Rodriguez-Menendez, V.; Oggioni, N.; Näsström, J.; Marmiroli, P.; Cavaletti, G. Calmangafodipir Reduces Sensory Alterations and Prevents Intraepidermal Nerve Fibers Loss in a Mouse Model of Oxaliplatin Induced Peripheral Neurotoxicity. Antioxidants 2020, 9, 594.

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