Metformin protects from oxaliplatin induced peripheral neuropathy in rats.

Autor:	Martinez NW; Center for Integrative Biology, Faculty of Sciences, Universidad Mayor de Chile, Santiago 8580745, Chile.; Department of Physiology, Faculty of Biology, Pontificia Universidad Católica de Chile, Santiago, Chile., Sánchez A; Department of Physiology, Faculty of Biology, Pontificia Universidad Católica de Chile, Santiago, Chile., Diaz P; Department of Physiology, Faculty of Biology, Pontificia Universidad Católica de Chile, Santiago, Chile., Broekhuizen R; Department of Hematology and Oncology, Pontificia Universidad Católica de Chile, Santiago, Chile., Godoy J; Department of Neurology, Pontificia Universidad Católica de Chile, Santiago, Chile., Mondaca S; Department of Hematology and Oncology, Pontificia Universidad Católica de Chile, Santiago, Chile., Catenaccio A; Center for Integrative Biology, Faculty of Sciences, Universidad Mayor de Chile, Santiago 8580745, Chile., Macanas P; Department of Hematology and Oncology, Pontificia Universidad Católica de Chile, Santiago, Chile., Nervi B; Department of Hematology and Oncology, Pontificia Universidad Católica de Chile, Santiago, Chile.; Millennium Institute on Immunology and Immunotherapy, Pontificia Universidad Católica de Chile, Santiago, Chile., Calvo M; Department of Physiology, Faculty of Biology, Pontificia Universidad Católica de Chile, Santiago, Chile., Court FA; Center for Integrative Biology, Faculty of Sciences, Universidad Mayor de Chile, Santiago 8580745, Chile.; FONDAP Center for Geroscience, Brain Health and Metabolism, Santiago 8580745, Chile.; Buck Institute for Research on Ageing, Novato, San Francisco, CA 94945, USA.
Jazyk:	angličtina
Zdroj:	Neurobiology of pain (Cambridge, Mass.) [Neurobiol Pain] 2020 May 22; Vol. 8, pp. 100048. Date of Electronic Publication: 2020 May 22 (Print Publication: 2020).
DOI:	10.1016/j.ynpai.2020.100048
Abstrakt:	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. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2020 Published by Elsevier Inc.)
Databáze:	MEDLINE
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