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The nitric oxide pathway is involved in the anti-inflammatory effect of the rutheniumcomplex [Ru(bpy)2(2-MIM)(NO)](PF6)3

2022; Elsevier BV; Volume: 921; Linguagem: Inglês

10.1016/j.ejphar.2022.174869

1879-0712

Isadora Oliveira de Carvalho, Cléo Vanessa Gomes de Queiroz, Gabriela Fernandes Oliveira Marques, Raquel Magalhães Castelo Branco Craveiro, Francisco Antônio Félix Xavier Júnior, Florêncio Sousa Gouveia Júnior, Luiz Gonzaga de França Lopes, Edna Maria Camelo Chaves, Helena Serra Azul Monteiro, Ana Maria Sampaio Assreuy, Janaína Serra Azul Monteiro Evangelista,

Inflammatory mediators and NSAID effects

Metal coordination complexes are chemotherapeutic and anti-inflammatory agents. The ruthenium complex FOR811A ([Ru(bpy)2(2-MIM)Cl](PF6)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.