Amifostine protects from the peripheral sensory neuropathy induced by oxaliplatin in mice.
Journal
Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas
ISSN: 1414-431X
Titre abrégé: Braz J Med Biol Res
Pays: Brazil
ID NLM: 8112917
Informations de publication
Date de publication:
2020
2020
Historique:
received:
05
05
2020
accepted:
08
08
2020
entrez:
23
9
2020
pubmed:
24
9
2020
medline:
13
11
2020
Statut:
epublish
Résumé
Sensory neuropathy is a dose-limiting side effect of oxaliplatin-based cancer treatment. This study investigated the antinociceptive effect of amifostine and its potential neuroprotective mechanisms on the oxaliplatin-related peripheral sensory neuropathy in mice. Oxaliplatin (1 mg/kg) was injected intravenously in Swiss albino male mice twice a week (total of nine injections), while amifostine (1, 5, 25, 50, and 100 mg/kg) was administered subcutaneously 30 min before oxaliplatin. Mechanical and thermal nociceptive tests were performed once a week for 49 days. Additionally, c-Fos, nitrotyrosine, and activating transcription factor 3 (ATF3) immunoexpressions were assessed in the dorsal root ganglia. In all doses, amifostine prevented the development of mechanical hyperalgesia and thermal allodynia induced by oxaliplatin (P<0.05). Amifostine at the dose of 25 mg/kg provided the best protection (P<0.05). Moreover, amifostine protected against neuronal hyperactivation, nitrosative stress, and neuronal damage in the dorsal root ganglia, detected by the reduced expression of c-Fos, nitrotyrosine, and ATF3 (P<0.05 vs the oxaliplatin-treated group). In conclusion, amifostine reduced the nociception induced by oxaliplatin in mice, suggesting the possible use of amifostine for the management of oxaliplatin-induced peripheral sensory neuropathy.
Identifiants
pubmed: 32965323
pii: S0100-879X2020001100601
doi: 10.1590/1414-431X202010263
pmc: PMC7510240
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Oxaliplatin
04ZR38536J
Amifostine
M487QF2F4V
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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