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

Autor: Pereira AF; Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil., Pereira LMS; Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil., Silva CMP; Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil., Freitas Alves BW; Department of Morphology, Morpho-functional Sciences Post Graduation Program, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil., Barbosa JS; Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil., Pinto FMM; Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil., Pereira AC; Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil., Silva KO; Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil., Pontes RB; Department of Physical Therapy, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil., Alencar NMN; Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil; Drug Research and Development Center, Federal University of Ceará, Fortaleza, CE, Brazil., Lima-Júnior RCP; Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil; Drug Research and Development Center, Federal University of Ceará, Fortaleza, CE, Brazil., Vale ML; Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil; Department of Morphology, Morpho-functional Sciences Post Graduation Program, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil; Drug Research and Development Center, Federal University of Ceará, Fortaleza, CE, Brazil. Electronic address: marianavale@yahoo.com.
Jazyk: angličtina
Zdroj: Neuroscience letters [Neurosci Lett] 2019 Sep 14; Vol. 709, pp. 134378. Date of Electronic Publication: 2019 Jul 17.
DOI: 10.1016/j.neulet.2019.134378
Abstrakt: Oxaliplatin 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 and ATF3 in the dorsal root ganglia and spinal cord. In addition, the oxaliplatin-associated nociception was significantly attenuated by metformin (P < 0.05), which also reduced the expression of c-Fos and ATF3 (P < 0.05). Therefore, metformin protected from the peripheral sensory neuropathy induced by oxaliplatin, which was confirmed by the reduction of c-Fos and ATF3 expression, two known neuronal activation and damage markers, respectively.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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