RESUMO
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.
Assuntos
Óxido Nítrico , Compostos Organometálicos , 2,2'-Dipiridil/análogos & derivados , Animais , Anti-Inflamatórios/efeitos adversos , Carragenina/efeitos adversos , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Compostos Organometálicos/farmacologia , Compostos Organometálicos/uso terapêuticoRESUMO
O sistema imune inato é capaz de promover respostas inflamatórias imediatas a lesões e atua como mecanismo inicial de defesa no corpo, estando seus defeitos associados a respostas exacerbadas, como na asma, ou a deficiências que levam a infecções graves,de aparecimento rápido. Assim, um melhor entendimento do processo inflamatório, bem como a utilização de moléculas modulatórias é de extrema importância. Polissacarídeos de plantas são reconhecidos por suas atividades antiviral, antitumoral, imunoestimulante, anti-inflamatória e anticoagulante. O extrato polissacarídico da casca de Caesalpinia ferrea(Caesalpinioideae), planta muito utilizada na medicina popular, possui efeito cicatrizante de feridas. O presente estudo avaliou a atividade inflamatória de extratos polissacarídicos obtidos da casca (EPC), vagens (EPV) e folhas (EPF) de Caesalpinia ferrea. A planta foi coletada em Custódio, município de Quixadá-CE, para extração dos polissacarídeos.Casca, vagens e folhas foram suspensas em metanol, ressuspensas em NaOH (0,1 M), neutralizadas com HCl (1 M) e avaliadas quanto aos teores de carboidrato e proteína. EPC, EPV e EPF foram testados em ratos Wistar fêmeas (150-250g) no modelo de edema de pata, induzido pela administração subcutânea (s.c.) intraplantar de dextrana (300 μg), carragenana (300 μg) ou dos extratos polissacarídicos (0,01, 0,1 e 1 mg/kg), e mensurado por plestismometria(0-8 horas). Os extratos polissacarídicos apresentaram elevado teor de carboidratos (EPC: 44%; EPV: 31%; EPF: 44%) e atividade edematogênica, com maior eficácia na dose de 1 mg/kg: EPC(0,75±0,05 mL vs. salina: 0,45±0,04 mL); EPV (0,46±0,06 mL; vs salina: 0,16±0,02 mL); EPF (0,3±0,01 mL; salina: 0,18±0,02 mL).
The innate system is able to promote immediate inflammatory response to injuries, acting as an initial defense mechanism, being its failing associated to exacerbated response as asthma or to deficiencies, that lead to rapid serious infection. Thus, the better understanding of this process as well as the use of modulatory molecules is extremely important. Plant polysaccharides are recognized for its antiviral, antitumor, immunostimulant, anti-inflammatory and anticoagulant effects. Polysaccharide extract obtained from Caesalpinia ferreabarks, a plant widely is used in folk medicine for wound healing, among others. This effect had been confirmed for the polysaccharide extract obtained from it barks. The present study evaluated the inflammatory activity of polyssaccharide extracts obtained from barks (PEB), pods (PEP) and leaves (PEL) of Caesalpinia ferrea. The plant was collected at Custódio, Quixadá-CE for obtention of the polyssaccharide extracts. Barks, pods and leaves were suspended in methanol, re-suspended in 0.1 M NaOH, neutralized with 1 M HCl and evaluated for carbohydrate and protein content. PEB, PEP and PEL were tested in female Wistar rats (150-250g) in the model of paw edema induced by subcutaneous (s.c.) intraplantar administration of dextran (300 μg), carrageenan (300 μg) or polyssaccharide extracts (0.01, 0.1 e 1 mg/kg) and measured by plesthysmometry (0 -8h). C. ferrea polyssaccharide extracts presented high content of carbohydrate (PEB: 44%; PEP: 31%; PEL: 44%) and edematogenic activity, with maximal efficacy at 1 mg/kg: PEB (0.75±0.05 mL vs. saline: 0.45±0.04 mL); PEP (0.46±0.06 mL; vs saline: 0.16±0.02 mL); PEL (0.3±0.01 mL; saline: 0.18±0.02 mL).
Assuntos
Feminino , Animais , Ratos , Caesalpinia/química , Celulite/terapia , Celulite/veterinária , Extratos Vegetais/uso terapêutico , Polissacarídeos/uso terapêutico , Inflamação/terapia , Inflamação/veterináriaRESUMO
O sistema imune inato é capaz de promover respostas inflamatórias imediatas a lesões e atua como mecanismo inicial de defesa no corpo, estando seus defeitos associados a respostas exacerbadas, como na asma, ou a deficiências que levam a infecções graves,de aparecimento rápido. Assim, um melhor entendimento do processo inflamatório, bem como a utilização de moléculas modulatórias é de extrema importância. Polissacarídeos de plantas são reconhecidos por suas atividades antiviral, antitumoral, imunoestimulante, anti-inflamatória e anticoagulante. O extrato polissacarídico da casca de Caesalpinia ferrea(Caesalpinioideae), planta muito utilizada na medicina popular, possui efeito cicatrizante de feridas. O presente estudo avaliou a atividade inflamatória de extratos polissacarídicos obtidos da casca (EPC), vagens (EPV) e folhas (EPF) de Caesalpinia ferrea. A planta foi coletada em Custódio, município de Quixadá-CE, para extração dos polissacarídeos.Casca, vagens e folhas foram suspensas em metanol, ressuspensas em NaOH (0,1 M), neutralizadas com HCl (1 M) e avaliadas quanto aos teores de carboidrato e proteína. EPC, EPV e EPF foram testados em ratos Wistar fêmeas (150-250g) no modelo de edema de pata, induzido pela administração subcutânea (s.c.) intraplantar de dextrana (300 μg), carragenana (300 μg) ou dos extratos polissacarídicos (0,01, 0,1 e 1 mg/kg), e mensurado por plestismometria(0-8 horas). Os extratos polissacarídicos apresentaram elevado teor de carboidratos (EPC: 44%; EPV: 31%; EPF: 44%) e atividade edematogênica, com maior eficácia na dose de 1 mg/kg: EPC(0,75±0,05 mL vs. salina: 0,45±0,04 mL); EPV (0,46±0,06 mL; vs salina: 0,16±0,02 mL); EPF (0,3±0,01 mL; salina: 0,18±0,02 mL).(AU)
The innate system is able to promote immediate inflammatory response to injuries, acting as an initial defense mechanism, being its failing associated to exacerbated response as asthma or to deficiencies, that lead to rapid serious infection. Thus, the better understanding of this process as well as the use of modulatory molecules is extremely important. Plant polysaccharides are recognized for its antiviral, antitumor, immunostimulant, anti-inflammatory and anticoagulant effects. Polysaccharide extract obtained from Caesalpinia ferreabarks, a plant widely is used in folk medicine for wound healing, among others. This effect had been confirmed for the polysaccharide extract obtained from it barks. The present study evaluated the inflammatory activity of polyssaccharide extracts obtained from barks (PEB), pods (PEP) and leaves (PEL) of Caesalpinia ferrea. The plant was collected at Custódio, Quixadá-CE for obtention of the polyssaccharide extracts. Barks, pods and leaves were suspended in methanol, re-suspended in 0.1 M NaOH, neutralized with 1 M HCl and evaluated for carbohydrate and protein content. PEB, PEP and PEL were tested in female Wistar rats (150-250g) in the model of paw edema induced by subcutaneous (s.c.) intraplantar administration of dextran (300 μg), carrageenan (300 μg) or polyssaccharide extracts (0.01, 0.1 e 1 mg/kg) and measured by plesthysmometry (0 -8h). C. ferrea polyssaccharide extracts presented high content of carbohydrate (PEB: 44%; PEP: 31%; PEL: 44%) and edematogenic activity, with maximal efficacy at 1 mg/kg: PEB (0.75±0.05 mL vs. saline: 0.45±0.04 mL); PEP (0.46±0.06 mL; vs saline: 0.16±0.02 mL); PEL (0.3±0.01 mL; saline: 0.18±0.02 mL).(AU)