Metformin reduces c-Fos and ATF3 expression in the dorsal root ganglia and protects against oxaliplatin-induced peripheral sensory neuropathy in mice

Publication date: Available online 17 July 2019Source: Neuroscience LettersAuthor(s): Anamaria Falcão Pereira, Lus Mário Silva Pereira, Cristiane Maria Pereira Silva, Bruno Wesley Freitas Alves, Jéssica Sales Barbosa, Francisco Maxwell Martins Pinto, Ana Carolina Pereira, Karla Oliveira Silva, Renata Bessa Pontes, Nylane Maria Nunes Alencar, Roberto César Pereira Lima-Júnior, Mariana Lima ValeAbstractOxaliplatin is a third-generation platinum drug commonly used as the first line treatment of metastatic colorectal cancer. Oxaliplatin-based anticancer regimens course with dose-limiting neurotoxicity. The pharmacological strategies used to manage such side effect are not totally effective. Metformin is an anti-diabetic drug that is described to negatively modulate painful diabetic neuropathy. Then, this study aimed to assess the effect of metformin in the oxaliplatin-induced peripheral sensory neuropathy in mice. For that purpose, Swiss male mice were injected with oxaliplatin (1, 2 or 4 mg/kg, i.v., twice a week with a total of nine injections) alone or in combination with daily administration of metformin (250 mg/kg, p.o.). Thermal and mechanical nociceptive tests were performed once a week for five weeks. Then, the animals were euthanized on day 35 post-first injection of oxaliplatin and the dorsal root ganglia were harvested for the assessment of c-Fos and ATF3 expressions. Oxaliplatin caused a nociceptive response accompanied by the increased expression of c-Fos an...
Source: Neuroscience Letters - Category: Neuroscience Source Type: research