RESUMO
Multiple myeloma (MM) is a B cell bone marrow neoplasia characterized by inflammation with an intense secretion of growth factors that promote tumor growth, cell survival, migration and invasion. The aim of this study was to evaluate the effects of pravastatin, a drug used to reduce cholesterol, in a MM cell line.Cell cycle and viability were determinate by Trypan Blue and Propidium Iodide. IL6, VEGF, bFGF and TGFß were quantified by ELISA and qRT-PCR including here de HMG CoA reductase. It was observed reduction of cell viability, increase of cells in G0/G1 phase of the cell cycle and reducing the factors VEGF and bFGF without influence on 3-Methyl-Glutaryl Coenzyme A reductase expression.The results demonstrated that pravastatin induces cell cycle arrest in G0/G1 and decreased production of growth factors in Multiple Myeloma cell line.
Assuntos
Fatores de Crescimento de Fibroblastos/genética , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Mieloma Múltiplo/metabolismo , Pravastatina/farmacologia , Fator A de Crescimento do Endotélio Vascular/genética , Anticolesterolemiantes/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Colesterol/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Humanos , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Abstract Multiple myeloma (MM) is a B cell bone marrow neoplasia characterized by inflammation with an intense secretion of growth factors that promote tumor growth, cell survival, migration and invasion. The aim of this study was to evaluate the effects of pravastatin, a drug used to reduce cholesterol, in a MM cell line.Cell cycle and viability were determinate by Trypan Blue and Propidium Iodide. IL6, VEGF, bFGF and TGFβ were quantified by ELISA and qRT-PCR including here de HMG CoA reductase. It was observed reduction of cell viability, increase of cells in G0/G1 phase of the cell cycle and reducing the factors VEGF and bFGF without influence on 3-Methyl-Glutaryl Coenzyme A reductase expression.The results demonstrated that pravastatin induces cell cycle arrest in G0/G1 and decreased production of growth factors in Multiple Myeloma cell line.
Resumo O Mieloma Múltiplo é uma neoplasia de linfócitos B da medula óssea, caracterizada por inflamação com uma intensa secreção de fatores de crescimento que promovem o aumento do volume do tumor, sobrevivência celular, migração e invasão. O objetivo deste estudo foi avaliar os efeitos da pravastatina, uma droga usada para reduzir o colesterol, em um linhagem de MM. O ciclo celular e viabilidade foram determinadas por Trypan Blue e iodeto de propídio. IL6, VEGF, bFGF e TGF foram quantificadas por ELISA e qRT-PCR, incluindo aqui de HMG CoA redutase. Observou-se a redução da viabilidade das células, aumento de células na fase G0/G1 do ciclo celular e redução no VEGF e bFGF, sem influência na expressão da enzima 3-Metil-Glutaril Coenzima A redutase. Os resultados demonstraram que a pravastatina induz parada no ciclo celular em G0/G1 e diminuição da produção de fatores de crescimento em várias linhas de células de Mieloma.
Assuntos
Humanos , Fatores de Crescimento de Fibroblastos/genética , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Mieloma Múltiplo/metabolismo , Pravastatina/farmacologia , Fator A de Crescimento do Endotélio Vascular/genética , Anticolesterolemiantes/farmacologia , Linhagem Celular , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Colesterol/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Abstract Multiple myeloma (MM) is a B cell bone marrow neoplasia characterized by inflammation with an intense secretion of growth factors that promote tumor growth, cell survival, migration and invasion. The aim of this study was to evaluate the effects of pravastatin, a drug used to reduce cholesterol, in a MM cell line.Cell cycle and viability were determinate by Trypan Blue and Propidium Iodide. IL6, VEGF, bFGF and TGF were quantified by ELISA and qRT-PCR including here de HMG CoA reductase. It was observed reduction of cell viability, increase of cells in G0/G1 phase of the cell cycle and reducing the factors VEGF and bFGF without influence on 3-Methyl-Glutaryl Coenzyme A reductase expression.The results demonstrated that pravastatin induces cell cycle arrest in G0/G1 and decreased production of growth factors in Multiple Myeloma cell line.(AU)
Resumo O Mieloma Múltiplo é uma neoplasia de linfócitos B da medula óssea, caracterizada por inflamação com uma intensa secreção de fatores de crescimento que promovem o aumento do volume do tumor, sobrevivência celular, migração e invasão. O objetivo deste estudo foi avaliar os efeitos da pravastatina, uma droga usada para reduzir o colesterol, em um linhagem de MM. O ciclo celular e viabilidade foram determinadas por Trypan Blue e iodeto de propídio. IL6, VEGF, bFGF e TGF foram quantificadas por ELISA e qRT-PCR, incluindo aqui de HMG CoA redutase. Observou-se a redução da viabilidade das células, aumento de células na fase G0/G1 do ciclo celular e redução no VEGF e bFGF, sem influência na expressão da enzima 3-Metil-Glutaril Coenzima A redutase. Os resultados demonstraram que a pravastatina induz parada no ciclo celular em G0/G1 e diminuição da produção de fatores de crescimento em várias linhas de células de Mieloma.(AU)
Assuntos
Animais , Mieloma Múltiplo/veterinária , Pravastatina/análise , Ciclo Celular , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento de FibroblastosRESUMO
Abstract Multiple myeloma (MM) is a B cell bone marrow neoplasia characterized by inflammation with an intense secretion of growth factors that promote tumor growth, cell survival, migration and invasion. The aim of this study was to evaluate the effects of pravastatin, a drug used to reduce cholesterol, in a MM cell line.Cell cycle and viability were determinate by Trypan Blue and Propidium Iodide. IL6, VEGF, bFGF and TGF were quantified by ELISA and qRT-PCR including here de HMG CoA reductase. It was observed reduction of cell viability, increase of cells in G0/G1 phase of the cell cycle and reducing the factors VEGF and bFGF without influence on 3-Methyl-Glutaryl Coenzyme A reductase expression.The results demonstrated that pravastatin induces cell cycle arrest in G0/G1 and decreased production of growth factors in Multiple Myeloma cell line.
Resumo O Mieloma Múltiplo é uma neoplasia de linfócitos B da medula óssea, caracterizada por inflamação com uma intensa secreção de fatores de crescimento que promovem o aumento do volume do tumor, sobrevivência celular, migração e invasão. O objetivo deste estudo foi avaliar os efeitos da pravastatina, uma droga usada para reduzir o colesterol, em um linhagem de MM. O ciclo celular e viabilidade foram determinadas por Trypan Blue e iodeto de propídio. IL6, VEGF, bFGF e TGF foram quantificadas por ELISA e qRT-PCR, incluindo aqui de HMG CoA redutase. Observou-se a redução da viabilidade das células, aumento de células na fase G0/G1 do ciclo celular e redução no VEGF e bFGF, sem influência na expressão da enzima 3-Metil-Glutaril Coenzima A redutase. Os resultados demonstraram que a pravastatina induz parada no ciclo celular em G0/G1 e diminuição da produção de fatores de crescimento em várias linhas de células de Mieloma.
RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Leaves of Pyrostegia venusta are popularly used to treat vitiligo; however, none in vivo study showed its ability. AIM OF THE STUDY: The overall objective of the present study was to evaluate the antiinflammatory and hyperpigmentant activities of hydroethanolic (HE) extract of leaves from P. venusta in animal models of vitiligo induced by croton oil and monobenzone. MATERIALS AND METHODS: The antiinflamatory and antioxidative effects of topical and oral administration of HE extract of P. venusta were evaluated in Swiss mice on edema model induced by croton oil, and further the N-acetyl-b-d-glucosaminidase (NAG) activity, cell infiltration, and cytokine and reactive species oxygen (ROS) levels. The involvement on mice pigmentation, cell infiltration and cytokine levels were evaluated on vitiligo model induced by monobenzone in C56BL/6 mice. RESULTS: HE of P. venusta by gavage (300 mg/kg) reduced NAG activity in 32.5 ± 5% on mouse ear edema induced by croton oil. Similarly, cell infiltration was lower (42.3 ± 5.9%) when compared to control group, as well as interleukin-1ß (IL-1ß), interleukin (IL-6) and tumor necrosis factor-α (TNF-α) levels, in 44.1 ± 9.7%, 71.9 ± 22.2% and to basal levels, respectively. Topical treatment with HE of P. venusta (10%) diminished cell infiltration (67.7 ± 7.1%) and ROS levels (total reduction). P. venusta either by gavage (300 mg/Kg) or topically (10%) increased epidermal melanin level (116.5 ± 13% and 100 ± 16.9%, respectively), diminished dermal depigmentation (36.0 ± 6.7% and 38.2 ± 6.2%, respectively), as well as tissue TNF-α levels (68.2 ± 11.6% and 99.2 ± 12.1%, respectively) and cell infiltration (basal levels and 94.3 ± 9.17%, respectively). However, only topical treatment with HE of P. venusta altered melanin specific marker in hair follicles. CONCLUSIONS: For the first time these data show that topical and oral administrations of P. venusta have significant antiinflammatory and hyperpigmentant effects, demonstrating different topical and systemic effects through two animal models. Together these models are capable to mimic several features founded in vitiligo, and the results support the ethnopharmacological use of P. venusta.
Assuntos
Anti-Inflamatórios/uso terapêutico , Bignoniaceae , Edema/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Vitiligo/tratamento farmacológico , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Óleo de Cróton , Citocinas/metabolismo , Edema/induzido quimicamente , Edema/metabolismo , Feminino , Hidroquinonas , Masculino , Melaninas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fitoterapia , Extratos Vegetais/farmacologia , Folhas de Planta , Espécies Reativas de Oxigênio/metabolismo , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/patologia , Vitiligo/induzido quimicamente , Vitiligo/metabolismoRESUMO
BACKGROUND AND OBJECTIVE: It has been demonstrated that periodontitis induces systemic inflammation, which may impair endothelial function leading to increased cardiovascular risk. The aim of this study was to evaluate the effect of simvastatin on systemic inflammatory markers and endothelial dysfunction induced by periodontitis. MATERIAL AND METHODS: Wistar rats were subjected to ligature-induced experimental periodontitis. Eight days after the procedure, the ligature and sham groups were randomly assigned to receive simvastatin or vehicle once a day until the 14th day, when the effects of acetylcholine and sodium nitroprusside on blood pressure were evaluated. Blood samples were collected and evaluated for plasma interleukin-6C, -reactive protein and lipids. The maxilla and mandible were removed for bone loss analysis. RESULTS: Simvastatin treatment reduced systemic inflammation and endothelial dysfunction induced by periodontitis. Furthermore, simvastatin improved the blood lipid profile and reduced alveolar bone loss. CONCLUSION: Simvastatin treatment, in addition to the improvement on serum lipid profile, may reduce other predictors of cardiovascular events associated with periodontitis.
Assuntos
Endotélio Vascular/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Mediadores da Inflamação/imunologia , Periodontite/imunologia , Sinvastatina/uso terapêutico , Acetilcolina/uso terapêutico , Perda do Osso Alveolar/imunologia , Perda do Osso Alveolar/prevenção & controle , Animais , Pressão Arterial/efeitos dos fármacos , Proteína C-Reativa/análise , Proteína C-Reativa/efeitos dos fármacos , Modelos Animais de Doenças , Endotélio Vascular/imunologia , Inflamação , Interleucina-6/sangue , Contagem de Leucócitos , Lipídeos/sangue , Masculino , Nitroprussiato/uso terapêutico , Periodontite/prevenção & controle , Distribuição Aleatória , Ratos , Ratos Wistar , Vasodilatadores/uso terapêuticoRESUMO
The analysis of comparative efficacy and safety of topical antifungals in the literature is restricted to the treatment of tinea pedis and onychomycosis. Therefore our objective was to evaluate and compare the efficacy and safety of topical antifungals used in the treatment of dermatomycosis, we performed a comprehensive search for randomized controlled trials (RCTs) in the following databases: Medline, Cochrane Central Register of Controlled Trials, EMBASE, Lilacs and International Pharmaceutical Abstracts, we identified studies that compared the use of topical antifungals with other antifungals or with placebo published up to July 2010 in English, Spanish or Portuguese. The quality of reporting was assessed according to the Jadad scale; only studies with a score of 3 or more were included. The outcomes evaluated were mycological cure at the end of treatment, sustained cure, occurrence of adverse events and tolerability, including withdrawals due to adverse events. A total of 104 RCTs satisfied the inclusion criteria, containing a total of 135 comparisons, with 55 out of 120 possible comparisons among the 16 drugs evaluated. Pooled data on efficacy showed that all the antifungals were better than placebo. There were no significant differences among antifungal classes. No differences were found in safety or tolerability in any direct comparison. Sensitivity analysis indicated the robustness of the findings. Our results indicate the clear superiority of topical antifungals over placebo but that there is no consistent difference among classes. Mixed treatment comparisons are necessary to rank antifungals, as direct comparisons among many of them are lacking.
Assuntos
Antifúngicos/administração & dosagem , Dermatomicoses/tratamento farmacológico , Administração Cutânea , Antifúngicos/efeitos adversos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
Leucurolysin-a (leuc-a), a 23 kDa non-hemorrhagic metalloproteinase, is found in venom of the viper Bothrops leucurus. Here, we examine the biological consequences of leuc-a, including thrombolytic activity, direct effects on endothelial cells in culture and edematogenic activity in vivo. We demonstrate fibrinolytic activity of leuc-a, in which the protease specifically degrades alpha, beta, and gamma-gamma chains. While not causing hemorrhaging, leuc-a does cause thrombolytic activities in whole blood clots. Endothelial cells are highly resistant to leuc-a in culture. Cell viability suffered only when cells were exposed to large quantities of the protease. Nevertheless, leuc-a induces changes in cell morphology. The impact of leuc-a on cell adhesion was confirmed by an adhesion assay, in which cell adhesion to fibronectin decreased due to leuc-a. This mild cellular impact is unlike that of crude venom, where lower concentrations triggered cell death and a greater reduction in cell adhesion. Also, leuc-a increased microvessel permeability with marked edema in mice peritoneum and foot pads. These effects are similar to those of other P-I class SVPMs. These in vivo effects were weaker when crude venom was tested. In conclusion, albeit not showing significant hemorrhagic activity, leuc-a can induce a prominent edema which appears to be significant in the local effects observed after B. leucurus venom accidents.
Assuntos
Bothrops/metabolismo , Venenos de Crotalídeos/toxicidade , Fibrinólise/efeitos dos fármacos , Metaloproteases/toxicidade , Análise de Variância , Animais , Adesão Celular/efeitos dos fármacos , Sobrevivência Celular , Células Cultivadas , Venenos de Crotalídeos/enzimologia , Venenos de Crotalídeos/isolamento & purificação , Venenos de Crotalídeos/metabolismo , Edema , Fibrina/metabolismo , Fibronectinas/metabolismo , Citometria de Fluxo , Humanos , Metaloproteases/isolamento & purificação , Metaloproteases/metabolismo , Microvasos/metabolismo , Coelhos , Trombina/metabolismoRESUMO
This study investigates the antinociception caused by i.p. and p.o. administration of ether fraction and the triterpene identified as urs-12-ene-3beta-16beta-diol, known as Brein, isolated from Protium kleinii in several models of nociception in mice. The systemic administration of ether fraction (0.3 to 10 mg/kg, i.p. or 3 to 60 mg/kg, p.o.) caused a dose-related antinociception when assessed against acetic acid-induced writhing, with mean ID50 values of 1.2 and 16.4 mg/kg, respectively. The ether fraction (5 to 60 mg/kg, i.p. or 30 to 300 mg/kg, p.o.) also produced dose-related inhibition of both phases of formalin induced licking. The mean ID50s values for the early phase were > 60.0 and 62.1 mg/kg, while for the late phase they were 15.4 and 60.0 mg/kg, respectively, given by i.p. and p.o. routes. The ether fraction (3 to 30 mg/kg, i.p. or 10 to 100 mg/kg, p.o.) produced significant inhibition of the neurogenic nociception caused by topical injection of capsaicin, with mean ID50 values of 6.2 and 16.0 mg/kg, respectively. Given orally (1 to 30 mg/kg) the ether fraction produced graded and pronounced inhibition of glutamate-induced hyperalgesia in mice with a mean ID50 value of 15.2 mg/kg. In contrast, the ether fraction failed to produce antinociception when assessed in the thermal model of pain, the tail flick and hot plate tests. The antinociception caused by the ether fraction, in contrast to that of morphine, was not reversed by naloxone when assessed in the formalin-induced licking. The ether fraction did not affect motor coordination or the core body temperature in mices. The triterpene Brein isolated from P. kleinii, given by i.p. route (10 to 100 mg/kg) produced dose-related inhibition of both phases of formalin induced-licking, with mean ID50s values of 15.3 and 20.6 for the early and the late phases, respectively. These data show that the active principle(s) present in the ether fraction from the resin of P. kleinii elicited pronounced antinociception when assessed by i.p. or p.o routes, against both inflammatory and neurogenic nociception. Such effects seem, at least in part, to be related to the presence of the triterpene Brein in the extract. The mechanisms responsible for the antinociceptive action are at this moment not completely understood, but the involvement of the opioid pathway seems unlikely.
Assuntos
Analgésicos/farmacologia , Dor/tratamento farmacológico , Triterpenos/farmacologia , Analgésicos/uso terapêutico , Animais , Relação Dose-Resposta a Droga , Camundongos , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Resinas Vegetais/farmacologia , Resinas Vegetais/uso terapêutico , Triterpenos/uso terapêuticoRESUMO
This study was conducted in order to determine the chemical composition and the possible antinociceptive effects in mice of some species of Phyllanthus in vitro. The methanolic extracts obtained from callus cultures of P. fraternus, P. stipulatus and P. caroliniensis caused significant inhibition in to the late phase of the formalin test, whereas the extract from P. urinaria inhibited both neurogenic and inflammatory phases of the test. Conventional chromatographic methods (TLC, GC) permitted the detection of some steroids or triterpenes, including beta-sitosterol, glochidonol and glochidone, which seem be responsible for the antinociceptive effects of the callus extracts studied.