RESUMO
INTRODUCTION: Inflammation is a physiological event that protects the organism against different factors that lead to loss of tissue homeostasis. Dihydropyridine (DHP) derivatives are heterocyclic compounds known for their different biological activities, including anti-inflammatory activities. OBJECTIVE: To evaluate the anti-inflammatory activity of 1,4-dihydropyridine (1,4-DHP) derivatives using anti-inflammatory models in vitro, in RAW264.7 cells induced by lipopolysaccharide (LPS) and in vivo using the acute lung injury (ALI) model in mice. RESULTS: Fifteen compounds derived from 1,4-DHP were tested in RAW264.7 cells for their cytotoxic effect and cell viability. Thereafter, only the six compounds that showed the highest cell viability were tested for the production or inhibition of the pro-inflammatory cytokine interleukin 6 (IL-6). The best compound (compound 4) was tested for its anti-inflammatory effects in vitro and in vivo, showing inhibition of nitric oxide (NO), pro-inflammatory cytokines, increased phagocytic activity, and an increase in IL-10 in vitro. In in vivo tests, compound 4 also reduces the levels of NO, myeloperoxidase (MPO) activity, leukocyte migration, and exudation, as well as reducing the levels of tumor necrosis factor-alpha (TNF-α) and IL-6 and preventing the loss in the lung architecture. CONCLUSION: This compound showed important anti-inflammatory activity, with a significant ability to reduce the production of pro-inflammatory mediators and increase the phagocytic activity of macrophages and anti-inflammatory mediator secretion (IL-10). These findings led us to hypothesize that this compound can repolarize the macrophage response to an anti-inflammatory profile (M2). Moreover, it was also able to maintain its anti-inflammatory activity in vivo experiments.
Assuntos
Di-Hidropiridinas , Interleucina-10 , Interleucina-6 , Camundongos , Animais , Citocinas , Anti-Inflamatórios/farmacologia , Fator de Necrose Tumoral alfa , Lipopolissacarídeos/farmacologia , Óxido NítricoRESUMO
Guanosine is a purinergic nucleoside that has been shown to have neuroprotective effects, mainly through its ability to modulate the glutamatergic system. An increase in pro-inflammatory cytokine levels triggers the activation of the enzyme indoleamine 2,3-dioxygenase 1 (IDO-1), leading to glutamatergic excitotoxicity, which has important roles in the pathophysiology of depression. The aim of this study was to investigate the possible antidepressant-like effects and underlying mechanisms of action of guanosine against lipopolysaccharide (LPS)-induced depression in a mouse model. Mice were orally pre-treated with saline (0.9% NaCl), guanosine (8 or 16 mg/kg), or fluoxetine (30 mg/kg) for 7 days before LPS (0.5 mg/kg, intraperitoneal) injection. One day after LPS injection, mice were subjected to the forced swim test (FST), tail suspension test (TST), and open field test (OFT). After the behavioral tests, mice were euthanized and the levels of tumor necrosis factor-α (TNF-α), IDO-1, glutathione, and malondialdehyde in the hippocampus were measured. Pretreatment with guanosine was able to prevent LPS- induced depressive-like behaviors in the TST and FST. In the OFT, no locomotor changes were observed with any treatment. Both guanosine (8 and 16 mg/kg/day) and fluoxetine treatment prevented the LPS-induced increase in TNF-α and IDO expression and lipid peroxidation as well as decrease of reduced glutathione levels in the hippocampus. Taken together, our findings suggest that guanosine may have neuroprotective effects against LPS-induced depressive-like behavior through preventing oxidative stress and the expression of IDO-1 and TNF-α in the hippocampus.
Assuntos
Depressão , Fármacos Neuroprotetores , Camundongos , Animais , Depressão/induzido quimicamente , Depressão/tratamento farmacológico , Depressão/metabolismo , Lipopolissacarídeos/farmacologia , Fluoxetina/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Guanosina/farmacologia , Fármacos Neuroprotetores/farmacologia , Comportamento Animal , Hipocampo/metabolismoRESUMO
The present study evaluated the antidepressant-like effects of vilazodone using the tail suspension test in mice. We also investigated the contribution of kynurenine pathway and N-methyl-d-aspartate receptors to this effect. For this purpose, we pretreated animals with sub-effective doses of L-kynurenine, 3-hydroxykynurenine, or quinolinic acid. We then assessed the immobility time, an indicative measure of depressive-like behavior, in the tail suspension test. We also evaluated the possible effects of sub-effective doses of vilazodone combined with sub-effective doses of ketamine (N-methyl-d-aspartate receptor antagonist) in a separate group. Vilazodone (3mg/kg, intraperitoneal) significantly reduced immobility time in the tail suspension test. L-kynurenine (1.7 mg/kg, intraperitoneal), 3-hydroxykynurenine (10 mg/kg, intraperitoneal), and quinolinic acid (3 nmol/site, intracerebroventricular) significantly increased the immobility time in the tail suspension test. The antidepressant-like effects of vilazodone (3mg/kg, intraperitoneal) were inhibited by pre-treatment with non-effective doses of L-kynurenine (0.83 mg/kg, intraperitoneal), 3-hydroxykynurenine (3.33 mg/kg, intraperitoneal), or quinolinic acid (1 nmol/site, intracerebroventricular). Pretreatment of mice with sub-effective doses of ketamine (1 mg/kg, intraperitoneal) optimized the action of a sub-effective dose of vilazodone (0.3mg/kg, intraperitoneal) and reduced the immobility time in the tail suspension test. None of the drugs used in this study induced any changes in locomotor activity in the open field test. The results showed that vilazodone induced an antidepressant-like effect in the tail suspension test, which may be mediated through an interaction with the kynurenine pathway and N-methyl-d-aspartate receptors.
Assuntos
Ketamina , Receptores de N-Metil-D-Aspartato , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Depressão/metabolismo , Elevação dos Membros Posteriores/métodos , Ketamina/farmacologia , Cinurenina/farmacologia , Camundongos , Ácido Quinolínico , Natação , Cloridrato de Vilazodona/farmacologiaRESUMO
Abstract Objective: To evaluate the parameters associated with quality of life in patients with Paget's disease of bone. Methods: Patients with Paget's disease of bone were evaluated with SF-36 and WHOQOL-bref questionnaires. Patients with other diseases that could cause significant impairment of their quality of life were excluded. We searched for correlations between the results and: age, time from diagnosis, type of involvement, pain related to Paget's disease of bone, limitation to daily activities, deformities, bone specific alkaline phosphatase, the extent of involvement and treatment. Results: Fifty patients were included. Results of the SF-36 total score and its domains, physical and mental health, were significantly correlated with bone pain and deformities. Marital status was significantly correlated with the SF-36 total score and Mental Health Domain. BAP levels and disease extension were significantly correlated to SF-36 Physical Health Domain. After multivariate analysis, the only parameters that remained significantly associated with the SF-36 total score and to its Mental Health and Physical Health Domains were pain and marital status.The WHOQOL-bref total score was significantly associated with pain, physical impairment and deformities. WHOQOL-bref Domain 1 (physical) score was significantly associated with marital status, pain and deformities, while Domain 2 (psychological) score was associated with marital status, physical impairment and kind of involvement. After multivariate analysis, the presence of pain, deformities, and marital status were significantly associated with results of the WHOQOL-bref total score and its Domain 1. WHOQOL-bref domain 2 results were significantly predicted by pain and marital status. Conclusion: The main disease-related factor associated with SF-36 results in Paget's disease of bone patients was bone pain, while bone pain and deformities were associated with WHOQOL-bref.
Resumo Objetivo: Avaliar os parâmetros associados à qualidade de vida em pacientes com doença de Paget óssea (DPO). Métodos: Avaliaram-se pacientes com DPO com os questionários SF-36 e WHOQOL-bref. Excluíram-se pacientes com outras doenças que pudessem causar comprometimento significativo da qualidade de vida. Buscou-se por correlações entre os resultados e idade, tempo de diagnóstico, tipo de envolvimento, dor relacionada com a DPO, limitação às atividades diárias, deformidades, fosfatase alcalina específica do osso, extensão do envolvimento e tratamento. Resultados: Incluíram-se 50 pacientes. Os resultados da pontuação total do SF-36 e seus domínios, saúde física e saúde mental, se correlacionaram significativamente com a dor óssea e deformidades. O estado civil se correlacionou significativamente com a pontuação total do SF-36 e com seu domínio saúde mental. Os níveis de BAP e a extensão da doença se correlacionaram significativamente com o domínio saúde física do SF-36. Depois da análise multivariada, os únicos parâmetros que permaneceram significativamente associados à pontuação total do SF-36 e aos seus domínios saúde mental e saúde física foram a dor e o estado civil. A pontuação total do WHOQOL-bref esteve significativamente associada à dor, ao comprometimento físico e a deformidades. O escore do Domínio 1 (físico) do WHOQOL-bref esteve significativamente associado ao estado civil, dor e deformidades, enquanto o Domínio 2 (psicológico) esteve associado ao estado civil, comprometimento físico e tipo de envolvimento. Depois da análise multivariada, a presença de dor, deformidades e estado civil esteve significativamente associada à pontuação total do WHOQOL-bref e à pontuação do seu Domínio 1. Os resultados do WHOQOL-bref 2 foram significativamente preditos pela dor e pelo estado civil. Conclusão: O principal fator associado aos escores do SF-36 foi a dor óssea, enquanto a dor óssea e as deformidades estiveram associadas ao WHOQOL-bref.
Assuntos
Humanos , Masculino , Feminino , Idoso , Osteíte Deformante/psicologia , Qualidade de Vida , Osteíte Deformante/complicações , Osteíte Deformante/fisiopatologia , Osteoartrite/complicações , Dor/complicações , Nível de Saúde , Inquéritos e Questionários , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To evaluate the parameters associated with quality of life in patients with Paget's disease of bone. METHODS: Patients with Paget's disease of bone were evaluated with SF-36 and WHOQOL-bref questionnaires. Patients with other diseases that could cause significant impairment of their quality of life were excluded. We searched for correlations between the results and: age, time from diagnosis, type of involvement, pain related to Paget's disease of bone, limitation to daily activities, deformities, bone specific alkaline phosphatase, the extent of involvement and treatment. RESULTS: Fifty patients were included. Results of the SF-36 total score and its domains, physical and mental health, were significantly correlated with bone pain and deformities. Marital status was significantly correlated with the SF-36 total score and Mental Health Domain. BAP levels and disease extension were significantly correlated to SF-36 Physical Health Domain. After multivariate analysis, the only parameters that remained significantly associated with the SF-36 total score and to its Mental Health and Physical Health Domains were pain and marital status. The WHOQOL-bref total score was significantly associated with pain, physical impairment and deformities. WHOQOL-bref Domain 1 (physical) score was significantly associated with marital status, pain and deformities, while Domain 2 (psychological) score was associated with marital status, physical impairment and kind of involvement. After multivariate analysis, the presence of pain, deformities, and marital status were significantly associated with results of the WHOQOL-bref total score and its Domain 1. WHOQOL-bref domain 2 results were significantly predicted by pain and marital status. CONCLUSION: The main disease-related factor associated with SF-36 results in Paget's disease of bone patients was bone pain, while bone pain and deformities were associated with WHOQOL-bref.
Assuntos
Osteíte Deformante/psicologia , Qualidade de Vida , Idoso , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Osteíte Deformante/complicações , Osteíte Deformante/fisiopatologia , Osteoartrite/complicações , Dor/complicações , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: Clinical and experimental evidences indicate that intrauterine inflammation during pregnancy is associated to brain damage. The objective of this study is to determine the effects of lipopolysaccharide in temperature, cytokine production and sickness behavior of pregnant dams. METHODS: A single i.p. injection of lipopolysaccharide (LPS) (50, 150 or 300 µg/kg) was administered on E18. Controls received isotonic saline. Body temperature was controlled before and 3 h after injections. Animals' behavior was assessed by the OF test 3 h following treatment. Animals were sacrificed for leukocyte, IL-1ß and TNF-α determination. Placental tissue and abortion were also examined. RESULTS: LPS administration elicited hypothermia. Abortion was observed in LPS 150 and 300 µg/kg. Leukocyte levels were significantly lower with LPS 300 µg/kg than in controls. LPS induced dose-dependent impairment in animals' locomotion. IL-1ß serum and amniotic fluid were higher than the saline, and TNF-α serum and amniotic fluid increased when compared to controls. Placental histopathologic abnormality was not found. CONCLUSION: LPS induces dose-dependent sickness behavior and hypothermia in pregnant mice. Our findings suggest that the presence of inflammation may be a causative factor for premature labor and that Escherichia coli antigens modify the concentration of pro-inflammatory agents in circulatory system and intra-uterine environment.
Assuntos
Aborto Espontâneo/induzido quimicamente , Comportamento de Doença/efeitos dos fármacos , Inflamação/induzido quimicamente , Lipopolissacarídeos/administração & dosagem , Aborto Espontâneo/imunologia , Animais , Temperatura Corporal , Relação Dose-Resposta a Droga , Feminino , Inflamação/imunologia , Injeções Intravenosas , Masculino , Camundongos , Atividade Motora , Gravidez , Complicações na Gravidez/induzido quimicamente , Complicações na Gravidez/imunologiaRESUMO
AIMS: Recurrent infections and activation of the inflammatory response affect the prognosis of cystic fibrosis (CF). We investigated the relationship between inflammatory response, infection, and pulmonary function in CF. MAIN METHODS: A clinical-cross-sectional study was conducted with 86 subjects: control group (CG, n=31, the same age and sex of the CF group), and CF group (CFG, n=55, age: 1-16 years), further distributed into CFG negative or positive bacteriology (CFGB(-)/CFGB(+)), and CFG negative or positive Pseudomonas aeruginosa (CFGPa(-)/CFGPa(+)). Using the Wald test, multiple linear regression (95% confidence interval) was performed between CG and CFG, and between CG and each of the CF subgroups (CFGB(-)/CFGB(+) and CFGPa(-)/CFGPa(+)). The inflammatory markers evaluated were myeloperoxidase (MPO), adenosine deaminase (ADA) activities, interleukin-1beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), nitric oxide metabolites (NOx) levels, and total and differential leukocyte counts. KEY FINDINGS: After adjusting for sex and age, CFG compared to CG revealed an increase of MPO, IL-1ß (P<0.001 in all subgroups), and CRP: CFG (P=0.002), CFGB(-) (P=0.007), CFGB(+) (P=0.009), CFGPa(-) (P=0.004) and CFGPa(+) (P=0.020). NOx (P=0.001, P<0.001), leukocytes (P=0.002, P=0.001), and neutrophils (P=0.003, P<0.001) were increased in CFGB(+) and CFGPa(+), respectively. A negative correlation between FEV1 and leukocytes (P=0.008) and FEV1 and neutrophils (P=0.031) resulted in CFG. SIGNIFICANCE: The inflammatory response characterized by the increase of MPO, IL-1ß, and CRP is determinant for CF. Also leukocytosis due to neutrophilia determines the pulmonary function deficiency in this disease.
Assuntos
Fibrose Cística/complicações , Pneumonia/complicações , Infecções por Pseudomonas/complicações , Pseudomonas aeruginosa/imunologia , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Fibrose Cística/diagnóstico , Fibrose Cística/imunologia , Fibrose Cística/microbiologia , Feminino , Humanos , Lactente , Pulmão/imunologia , Pulmão/microbiologia , Masculino , Pneumonia/diagnóstico , Pneumonia/imunologia , Pneumonia/microbiologia , Infecções por Pseudomonas/diagnóstico , Infecções por Pseudomonas/imunologia , Pseudomonas aeruginosa/isolamento & purificaçãoRESUMO
The effect of betulinic acid on glycemia and its mechanism of action compared with 1,25(OH)2 vitamin D3 in rat muscle were investigated. Betulinic acid improved glycemia, induced insulin secretion and increased the glycogen content and glucose uptake in muscle tissue. Additionally, the integrity of both PI3K and the cytoskeleton is necessary for the stimulatory action of betulinic acid in glucose uptake. The genomic effect was apparent, since cycloheximide and PD98059 nullified the stimulatory effect of betulinic acid on glucose uptake. Therefore, although this compound did not modify the DNA transcription, the protein translation was significantly improved. Also, betulinic acid increased the GLUT4 immunocontent and its translocation was corroborated by GLUT4 localization at the plasma membrane (after 180 min). On the other hand, the effect of 1,25(OH)2 vitamin D3 on glucose uptake is not mediated by PI3K and microtubule activity. In contrast, the nuclear activity of 1,25(OH)2 vitamin D3 is necessary to trigger glucose uptake. In addition, the increased DNA transcription and GLUT4 immunocontent provide evidence of a mechanism by which 1,25(OH)2 vitamin D3 contributes to glycemia. In conclusion, betulinic acid acts as an insulin secretagogue and insulinomimetic agent via PI3K, MAPK and mRNA translation and partially shares the genomic pathway with 1,25(OH)2 vitamin D3 to upregulate the GLUT4. In summary, betulinic acid regulates glycemia through classical insulin signaling by stimulating GLUT4 synthesis and translocation. In addition, it does not cause hypercalcemia, which is highly significant from the drug discovery perspective.
Assuntos
Glucose/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Triterpenos/farmacologia , Vitamina D/análogos & derivados , Animais , Transporte Biológico , Glicemia/metabolismo , Cálcio/sangue , Glucose/administração & dosagem , Glucose/farmacocinética , Transportador de Glucose Tipo 4/metabolismo , Glicogênio/metabolismo , Homeostase/efeitos dos fármacos , Hiperglicemia/sangue , Hiperglicemia/tratamento farmacológico , Hiperglicemia/metabolismo , Insulina/sangue , Insulina/metabolismo , L-Lactato Desidrogenase/sangue , Masculino , Triterpenos Pentacíclicos , Transporte Proteico/efeitos dos fármacos , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Vitamina D/farmacologia , Ácido BetulínicoRESUMO
The acute effect of crude extract, n-butanol and aqueous residual fractions of Musa x paradisiaca L., Musaceae, leaves on glycemia, serum insulin secretion and glycogen content in an in vivo approach was evaluated. In addition, the in vitro effect on disaccharidases activity and albumin glycation was studied. The crude extract and fractions, n-butanol and aqueous residual, reduced glycemia and increased liver glycogen content in hyperglycemic rats, inhibited maltase activity and the formation of advanced glycation end-products in vitro. Also, a significant increase in insulin secretion and muscle glycogen content in hyperglycemic rats was observed with oral administration of the n-butanol fraction. Phytochemical analysis demonstrated the presence of rutin in crude extract and fractions of M. x paradisiaca leaves as the major compound. These beneficial effects on the regulation of glucose homeostasis observed for M. x paradisiaca leaves and the presence of rutin as the major compound indicate potential anti-diabetic properties, since previous studies have been reported that rutin can modulate glucose homeostasis.
RESUMO
UNLABELLED: ETHNO-PHARMACOLOGICAL RELEVANCE: Chenopodium ambrosioides (Amarantaceae) is an annual or perennial plant popularly known as 'erva de Santa Maria', 'mastruço' and 'erva-do-formigueiro'. This herb is used in folk medicine in the form of teas, poultices and infusions for inflammatory problems, contusions and lung infections, and as an anthelmintic and anti-fungal. AIM OF THE STUDY: The aim of the present study was to further the understanding of the anti-nociceptive, anti-inflammatory and wound healing effects of ethanol extract (EE) obtained from the leaves and stems of Chenopodium ambrosioides in animal models of acute pain, inflammation and wound healing, thus supporting its medicinal use for the treatment of pain and inflammatory conditions MATERIALS AND METHODS: The anti-nociceptive activity of EE (150-500 mg/kg) was evaluated using the nociception induced by formalin (2.5%), prostaglandin-E(2) (PGE2; 3 nmol/paw), capsaicin (CAP, 1.6 µg/paw) and bradykinin (BK, 10 nmol/paw). The anti-inflammatory activity of EE (150-500 mg/kg) was evaluated in carrageenan- (Cg, 300 µg/paw), PGE(2)- (3 nmol/paw), substance P- (SP, 20 nmol/paw) and BK- (3 nmol/paw) induced paw oedema. The topical anti-inflammatory activity of EE (1%, 3% and 5%) was evaluated in arachidonic acid- (AA, 2mg/ear), oil croton- (1 µg/ear) and CAP- (250 µg/ear) induced ear oedema. The effect of this extract in the inhibition of the influx of neutrophil, myeloperoxidase (MPO) and adenosine-deaminase (ADA) activities and nitric oxide (NO) and TNF-á levels was also determined using the mouse of pleurisy induced by Cg. The excision wound model in rats was used to evaluate the wound healing efficacy of EE (1%, 3% and 5%). To exclude the possible non-specific muscle relaxant or sedative effects of EE, mice motor performance was also evaluated with the rota-rod test. RESULTS: EE (5% per ear) was effective in reducing ear oedema induced by croton oil by 78.09%, CAP by 70.85% and AA by 77.02%. EE (500 mg/kg; p.o.) also significantly inhibited paw oedema induced by Cg by 40%, PGE(2) by 51%, SP by 56% and BK by 57%. EE (500 mg/kg; p.o.) inhibited the cell influx of leucocytes by 78% and neutrophils by 53%, MPO activity by 62.22% and ADA activity by 23.07%, as well as NO by 77.77% and TNF-á levels by 50% in the fluid leakage due to the carrageenan-induced pleurisy. EE also inhibited the formalin-induced nociceptive in both phases of pain (neurogenic and inflammatory) at a dose of 500 mg/kg, resulting in inhibitions of 77.39% and 95.60%, respectively. EE (500 mg/kg; p.o.) was also effective in inhibiting the nociception induced by PGE(2) (68%), CAP (53%) and BK (32%). Topical application of EE (5%) on excision wounds caused a significant reduction in wound area when compared with the untreated controls. Finally, treatment with EE (150-500 mg/kg) did not show any significant alterations in motor performance or body temperature compared with the control group. CONCLUSIONS: The results, including the inhibition of mediators (BK, NO, SP, PGE(2) and TNF-á) and enzyme (MPO and ADA) activity, validate the use of the plant under study for therapeutic treatment of anti-inflammatory, painful and wound healing processes.
Assuntos
Analgésicos/uso terapêutico , Anti-Inflamatórios/análise , Anti-Inflamatórios/uso terapêutico , Chenopodium ambrosioides/química , Fitoterapia/métodos , Extratos Vegetais/uso terapêutico , Analgésicos/análise , Analgésicos/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Temperatura Corporal/efeitos dos fármacos , Modelos Animais de Doenças , Edema/induzido quimicamente , Edema/tratamento farmacológico , Etanol/química , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Monoterpenos/análise , Monoterpenos/isolamento & purificação , Dor/induzido quimicamente , Dor/tratamento farmacológico , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Caules de Planta/química , Pleurisia/induzido quimicamente , Pleurisia/tratamento farmacológico , Pleurisia/metabolismo , Teste de Desempenho do Rota-Rod/métodos , Cicatrização/efeitos dos fármacosRESUMO
The aim of this study was to investigate the anti-inflammatory efficacy of rosiglitazone (ROSI) in a pleurisy model of carrageenan-induced inflammation. Efficacy was monitored in the mouse pleural cavity by evaluating leukocyte migration, exudate concentration, and myeloperoxidase (MPO) and adenosine deaminase (ADA) activities concomitantly with nitrate/nitrite (NOx), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), interleukin-17A (IL-17A), and vascular endothelial growth factor-alpha (VEGF-α) levels 4 and 48 h after pleurisy induction. In both phases (4 and 48 h) of pleurisy, ROSI inhibited all the inflammation parameters that were tested (p<0.05). These results provide evidence that ROSI was efficacious in inhibiting pro-inflammatory mediators. These anti-inflammatory effects are assumed to mainly result from the inhibition of products released from activated leukocytes, such as MPO, ADA, NOx, TNF-α, IL-1ß, IL-17A, and VEGF-α.
Assuntos
Inflamação/tratamento farmacológico , PPAR gama/agonistas , Pleurisia/tratamento farmacológico , Tiazolidinedionas/farmacologia , Adenosina Desaminase/metabolismo , Animais , Carragenina , Movimento Celular , Modelos Animais de Doenças , Inflamação/induzido quimicamente , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Interleucina-17/metabolismo , Interleucina-1beta/metabolismo , Leucócitos Mononucleares/metabolismo , Camundongos , Peroxidase/metabolismo , Pleurisia/induzido quimicamente , Pleurisia/imunologia , Rosiglitazona , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Several studies have shown that the anti-inflammatory effect of Pioglitazone extends beyond the cardiovascular system. This study examines the anti-inflammatory effect of Pioglitazone in comparison to reference drugs (Dexamethasone and Indomethacin) in the mouse model of pleurisy induced by carrageenan which is characterized by two distinct phases (4 and 48 h) of inflammation. Pioglitazone (20 and 50 mg/kg, i.p., 0.5 h before pleurisy) inhibited both neutrophil (4 h) and mononuclears (48 h) influxes (P<0.01), but not exudation (P>0.05). While one dose of Pioglitazone was effective in inhibiting inflammation at 4 h, additional doses (10 or 20 mg/kg, i.p., 0.5 h before pleurisy induction followed by either a second dose at 24 h after the first one or two further doses at 12 h of time interval after the first one) were necessary to elicit inhibition of the second (48 h) inflammation phase. These effects were associated with a marked decrease in adenosine-deaminase (ADA) activity, tumor necrosis factor-alpha (TNF-alpha) and interleukin 1-beta (IL-1beta) levels (P<0.01). Myeloperoxidade (MPO) activity was inhibited only at 4 h (P<0.05). By contrast, reference drugs were able to inhibit all the studied inflammatory parameters (P<0.05). These results demonstrated an interesting anti-inflammatory property of this thiazolidinedione class and strengthen prior evidence that PPAR pathways constitute another important route of inflammatory process inhibition of this pleurisy model.