Metformin protects from oxaliplatin induced peripheral neuropathy in rats
| Autor: | Bruno Nervi, J. Godoy, Felipe A. Court, Sebastian Mondaca, Richard Broekhuizen, A. Sánchez, Margarita Calvo, Nicolas W. Martinez, P. Macanas, Alejandra Catenaccio, P. Diaz |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
endocrine system diseases Peripheral neuropathy Neuroscience (miscellaneous) Pharmacology Neuroprotection lcsh:RC321-571 03 medical and health sciences 0302 clinical medicine medicine Original Research Article lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Dysesthesia business.industry nutritional and metabolic diseases medicine.disease digestive system diseases Metformin Oxaliplatin 030104 developmental biology Anesthesiology and Pain Medicine Allodynia Gliosis Hyperalgesia Neurology (clinical) medicine.symptom business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Neurobiology of Pain Neurobiology of Pain, Vol 8, Iss, Pp 100048-(2020) |
| ISSN: | 2452-073X |
| Popis: | Highlights • After oxaliplatin treatment rats developed mechanical and cold hyperalgesia. • We observed intraepidermal nerve fiber degeneration, and mild spinal cord gliosis. • Co treatment with Metformin could prevent all these pathological outcomes. • This suggests metformin as a candidate drug to prevent oxaliplatin-induced neuropathy. Oxaliplatin is a commonly used drug to treat cancer, extending the rate of disease-free survival by 20% in colorectal cancer. However, oxaliplatin induces a disabling form of neuropathy resulting in more than 60% of patients having to reduce or discontinue oxaliplatin, negatively impacting their chance of survival. Oxaliplatin-induced neuropathies are accompanied by degeneration of sensory fibers in the epidermis and hyperexcitability of sensory neurons. These morphological and functional changes have been associated with sensory symptoms such as dysesthesia, paresthesia and mechanical and cold allodynia. Various strategies have been proposed to prevent or treat oxaliplatin-induced neuropathies without success. The anti-diabetic drug metformin has been recently shown to exert neuroprotection in other chemotherapy-induced neuropathies, so here we aimed to test if metformin can prevent the development of oxaliplatin-induced neuropathy in a rat model of this condition. Animals treated with oxaliplatin developed significant intraepidermal fiber degeneration, a mild gliosis in the spinal cord, and mechanical and cold hyperalgesia. The concomitant use of metformin prevented degeneration of intraepidermal fibers, gliosis, and the altered sensitivity. Our evidence further supports metformin as a new approach to prevent oxaliplatin-induced neuropathy with a potential important clinical impact. |
| Databáze: | OpenAIRE |
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