Evidence for the involvement of TNF-α, IL-1β and IL-10 in the antinociceptive and anti-inflammatory effects of indole-3-guanylhydrazone hydrochloride, an aromatic aminoguanidine, in rodents.

Autor: Sandes SMS; Laboratory of Neuroscience and Pharmacological Assay (LANEF), Graduate Program in Health Sciences, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil., Heimfarth L; Laboratory of Neuroscience and Pharmacological Assay (LANEF), Graduate Program in Health Sciences, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil., Brito RG; Laboratory of Neuroscience and Pharmacological Assay (LANEF), Graduate Program in Health Sciences, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil., Santos PL; Laboratory of Neuroscience and Pharmacological Assay (LANEF), Graduate Program in Health Sciences, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil., Gouveia DN; Laboratory of Neuroscience and Pharmacological Assay (LANEF), Graduate Program in Health Sciences, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil., Carvalho AMS; Laboratory of Neuroscience and Pharmacological Assay (LANEF), Graduate Program in Health Sciences, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil., Quintans JSS; Laboratory of Neuroscience and Pharmacological Assay (LANEF), Graduate Program in Health Sciences, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil., da Silva-Júnior EF; Chemistry and Biotechnology Institute, Federal University of Alagoas, Maceio, Alagoas, Brazil., de Aquino TM; Chemistry and Biotechnology Institute, Federal University of Alagoas, Maceio, Alagoas, Brazil., França PHB; Laboratory of Medicinal Chemistry, Nursing and Pharmacy School, Federal University of Alagoas, Maceio, Alagoas, Brazil., de Araújo-Júnior JX; Laboratory of Medicinal Chemistry, Nursing and Pharmacy School, Federal University of Alagoas, Maceio, Alagoas, Brazil., Albuquerque-Júnior RLC; Technology and Research Institute (ITP), Tiradentes University, Aracaju, Sergipe, Brazil., Zengin G; Department of Biology, Science Faculty, Selcuk University, Campus, Konya, Turkey., Schmitt M; CNRS, University of Strasbourg, Laboratoire d'Innovation Thérapeutique, UMR 7200, Laboratory of Excellence Médalis, Faculté de Pharmacie, 74, Route du Rhin, 67401, Illkirch Cedex, France., Bourguignon JJ; CNRS, University of Strasbourg, Laboratoire d'Innovation Thérapeutique, UMR 7200, Laboratory of Excellence Médalis, Faculté de Pharmacie, 74, Route du Rhin, 67401, Illkirch Cedex, France., Quintans-Júnior LJ; Laboratory of Neuroscience and Pharmacological Assay (LANEF), Graduate Program in Health Sciences, Federal University of Sergipe, São Cristóvão, Sergipe, Brazil. Electronic address: lucindo@pq.cnpq.br.
Jazyk: angličtina
Zdroj: Chemico-biological interactions [Chem Biol Interact] 2018 Apr 25; Vol. 286, pp. 1-10. Date of Electronic Publication: 2018 Feb 27.
DOI: 10.1016/j.cbi.2018.02.026
Abstrakt: Background: Indole-3-guanylhydrazone hydrochloride (LQM01) is a new derivative of aminoguanidine hydrochloride, an aromatic aminoguanidine.
Methods: Mice were treated with LQM01 (5, 10, 25 or 50 mg/kg, i.p.), vehicle (0.9% saline i.p.) or a standard drug. The mice were subjected to carrageenan-induced pleurisy, abdominal writhing induced by acetic acid, the formalin test and the hot-plate test. The model of non-inflammatory chronic muscle pain induced by saline acid was also used. Mice from the chronic protocol were assessed for withdrawal threshold, muscle strength and motor coordination. LQM01 or vehicle treated mice were evaluated for Fos protein.
Results: LQM01 inhibits TNF-α and IL-1β production, as well as leukocyte recruitment during inflammation process. The level of IL-10 in LQM01-treated mice increased in pleural fluid. In addition, LQM01 decreased the nociceptive behavior in the acetic acid induced writhing test, the formalin test (both phases) and increased latency time on the hot-plate. LQM01 treatment also decreased mechanical hyperalgesia in mice with chronic muscle pain, with no changes in muscle strength and motor coordination. LQM01 reduced the number of Fos positive cells in the superficial dorsal horn. This compound exhibited antioxidant properties in in vitro assays.
Conclusions: LQM01 has an outstanding anti-inflammatory and analgesic profile, probably mediated through a reduction in proinflammatory cytokines release, increase in IL-10 production and reduction in neuron activity in the dorsal horn of the spinal cord in mice.
General Significance: Beneficial effects of LQM01 suggest that it has some important clinical features and can play a role in the management of 'dysfunctional pain' and inflammatory diseases.
(Copyright © 2018 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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