1. The nitric oxide pathway is involved in the anti-inflammatory effect of the rutheniumcomplex [Ru(bpy)2(2-MIM)(NO)](PF6)3.
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Carvalho, Isadora Oliveira, Queiroz, Cléo Vanessa Gomes, Marques, Gabriela Fernandes Oliveira, Craveiro, Raquel Magalhães Castelo Branco, Xavier Júnior, Francisco Antônio Félix, Gouveia Júnior, Florêncio Sousa, Lopes, Luiz Gonzaga de França, Chaves, Edna Maria Camelo, Monteiro, Helena Serra Azul, Assreuy, Ana Maria Sampaio, and Evangelista, Janaina Serra Azul Monteiro
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NITRIC oxide , *ANTI-inflammatory agents , *RUTHENIUM compounds , *MAST cells , *TISSUE analysis , *NEUTROPHILS - Abstract
Metal coordination complexes are chemotherapeutic and anti-inflammatory agents. The ruthenium complex FOR811A ([Ru(bpy) 2 (2-MIM)Cl](PF 6) 3) FOR811A was evaluated in mice models of acute inflammation and behavioral tests. Animals received FOR811A (3, 10 or 30 mg/kg; i.p.), indomethacin (20 mg/kg; i.p.), L-NAME (20 mg/kg; i.v.) aminoguanidine (50 mg/kg; i.p.) or dexamethasone (0.5 mg/kg; s.c.) 30 min before inflammatory stimulation. Paw edema was induced by carrageenan (400 μg/paw), TNF-α or L-arginine (15 nmol/paw) (5 ng/paw) and evaluated by hydropletismometry 4 h later. Peritonitis was induced by carrageenan (500 μg; i.p.) and evaluated 4 h later for hypernociception and quantification of total/differential leukocytes, total protein reduced glutathione (GSH) and myeloperoxidase (MPO). FOR811A inhibited the paw edema induced by carrageenan at 3 (64%; p < 0.0001), 10 (73%; p < 0.0001) and 30 mg/kg (66%; p < 0.0001), and at 10 mg/kg that induced with L-arginine by 75% or TNF-α by 55% (p = 0.0012). Paw tissues histological analysis showed reduction in mast cells (46%; p = 0.0027), leukocyte infiltrate (66%; p < 0.0001), edema and hemorrhagic areas. Immunohistochemical evaluation revealed inhibition of iNOS (62%; p < 0.0001) and TNF-α (35%; p < 0.0001). In the peritonitis model FOR811A increased (2.8X; p < 0.0001) hypernociceptive threshold, reduced total leukocytes (29%; p < 0.0001), neutrophils (47%; p = 0.0003) and total proteins (36%; p = 0.0082). FOR811A also inhibited MPO (47%; p = 0.0296) and increased GSH (1.8X; p < 0.0001). In the behavioral tests, FOR811A reduced (30.6%) the number of crossings in the open field, and increased (16%) the number of falls in the Rota rod. Concluding, FOR811A presents anti-inflammatory and antioxidant effects, via nitric oxide pathway. • FOR811A is a ruthenium coordination complex presenting antiinflammatory action. • FOR811A inhibits mice acute inflammation involving TNFα and NO. • FOR811A inhibits acute inflammation via modulation of iNOS. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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