RESUMO
Exposure to low temperatures can be considered a stressor, which when applied for a specific time can lead to adaptive reactions. In our study we hypothesized that cold, when applied to the entire body, may be a factor that positively modifies the aging process of bones by improving the mechanisms related to the body's mineral balance. Taking the above into account, the aim of the study was to determine the concentration of calcium (Ca), magnesium (Mg), and phosphorus (P) in bones, and to examine bone density and concentrations of the key hormones for bone metabolism, namely parathyroid hormone (PTH), somatotropin (GH), 1,25-dihydroxyvitamin D3, 17-ß estradiol, testosterone (T) in plasma, and prostaglandin E2 (PGE2) in the bone of aging rats subjected to physical training in cold water. The animals in the experiment were subjected to a series of swimming sessions for nine weeks. Study group animals (male and female respectively) performed swimming training in cold water at 5 ± 2 °C and in water with thermal comfort temperature (36 ± 2 °C). Control animals were kept in a sedentary condition. Immersion in cold water affects bone mineral metabolism in aging rats by changing the concentration of Ca, Mg, and P in the bone, altering bone mineral density and the concentration of key hormones involved in the regulation of bone mineral metabolism. The effect of cold-water immersion may be gender-dependent. In females, it decreases Ca and Mg content in bones while increasing bone density and 17-ß estradiol and 1,25-dihydroxyvitamin D3 levels, and with a longer perspective in aging animals may be positive not only for bone health but also other estrogen-dependent tissues. In males, cold water swimming decreased PTH and PGE2 which resulted in a decrease in phosphorus content in bones (with no effect on bone density), an increase in 1,25-dihydroxyvitamin D3, and increase in T and GH, and may have positive consequences especially in bones and muscle tissue for the prevention of elderly sarcopenia.
Assuntos
Envelhecimento/fisiologia , Crioterapia/métodos , Esforço Físico/fisiologia , Animais , Densidade Óssea/efeitos dos fármacos , Osso e Ossos/química , Calcitriol/análise , Calcitriol/sangue , Cálcio/análise , Temperatura Baixa , Dinoprostona/análise , Estradiol/análise , Estradiol/sangue , Feminino , Hormônio do Crescimento/análise , Hormônio do Crescimento/sangue , Magnésio/análise , Masculino , Hormônio Paratireóideo/análise , Hormônio Paratireóideo/sangue , Fósforo/análise , Condicionamento Físico Animal/métodos , Plasma/química , Ratos , Ratos Wistar , Testosterona/análise , Testosterona/sangueRESUMO
Enterotoxigenic Escherichia coli (ETEC) infection is a major cause of death in children under the age of five in developing countries. ETEC (O78:H11:CFA/I:LT+:ST+) mechanism has been studied in detail with either heat labile (LT) or heat stable (ST) toxins using in vitro and in vivo models. However, there is no adequate information on ETEC pathogenesis producing both the toxins (LT, ST) in BALB/c mice model. In this study, female mice have been employed to understand ETEC H10407 infection induced changes in physiology, biochemical and immunological patterns up to seven days post-infection and the antidiarrhoeal effect of Simarouba amara (Aubl.) bark aqueous extract (SAAE) has also been looked into. The results indicate that BALB/c is sensitive to ETEC infection resulting in altered jejunum and ileum histomorphology. Withal, ETEC influenced cAMP, PGE2, and NO production resulting in fluid accumulation with varied Na+, K+, Cl-, and Ca2+ levels. Meanwhile, ETEC subverted expression of IL-1ß, intestine alkaline phosphatase (IAP), and myeloperoxidase (MPO) in jejunum and ileum. Our data also indicate the severity of pathogenesis reduction which might be due to attainment of equilibrium after reaching optimum rate of infection. Nevertheless, degree of pathogenesis was highly significant (p < 0.01) in all the studied parameters. Besides that, SAAE was successful in reducing the infectious diarrhoea by inhibiting ETEC H10407 in intestine (jejunum and ileum), and shedding in feces. SAAE decreased cAMP, PGE2, and fluid accumulation effectively and boosted the functional activity of immune system in jejunum and ileum IAP, MPO, IL-1ß, and nitric oxide.
Assuntos
Diarreia/tratamento farmacológico , Diarreia/microbiologia , Escherichia coli Enterotoxigênica/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Imunomodulação , Compostos Fitoquímicos/farmacologia , Fosfatase Alcalina/análise , Animais , AMP Cíclico/análise , Dinoprostona/análise , Eletrólitos/sangue , Escherichia coli Enterotoxigênica/patogenicidade , Infecções por Escherichia coli/imunologia , Infecções por Escherichia coli/microbiologia , Fezes/microbiologia , Feminino , Humanos , Íleo/imunologia , Íleo/microbiologia , Íleo/patologia , Interleucina-1beta/análise , Jejuno/imunologia , Jejuno/microbiologia , Jejuno/patologia , Camundongos , Camundongos Endogâmicos BALB C , Nitritos/análise , Fragmentos de Peptídeos/análise , Peroxidase/análise , Casca de Planta/química , Extratos Vegetais/farmacologia , Simarouba/químicaRESUMO
Polysaccharide from Ma-chi-xian (Portulacae oleracea L., POLP) was prepared and the therapeutic effect on dextran sodium sulfate-induced colitis mice was investigated in this study. The results of clinical activity score and H&E staining confirmed the therapeutic effect of POLP. POLP could diminished the symptoms of colitis and improve colon histopathological structure of the colitis mice. The expression levels of four cytokines were determined. The concentrations of PGE2 and IL-6 were downregulated by POLP treatment. The COX-2 protein expression levels and the STAT3 phosphorylation levels were detected. The results showed that these two protein levels were all increased in colitis and decreased after POLP treatment, indicating that these two proteins were closely related with the protective effect of POLP. Because the synthesis of PGE2 is catalyzed by COX-2 and phosphorylation of STAT3 can induce the expression of COX-2, it was concluded that STAT3 was a key protein related to the POLP exerting its activity in colitis.
Assuntos
Colite/tratamento farmacológico , Colo/efeitos dos fármacos , Medicamentos de Ervas Chinesas/uso terapêutico , Polissacarídeos/farmacologia , Portulaca/química , Animais , Colite/induzido quimicamente , Colo/patologia , Ciclo-Oxigenase 2/análise , Sulfato de Dextrana , Dinoprostona/análise , Interleucina-6/análise , Camundongos , Fosforilação , Fator de Transcrição STAT3/análiseRESUMO
Background: Maternal obesity is known to affect human milk composition. Long-chain polyunsaturated fatty acids (LCPUFA) are vital nutrients to the nervous system development and precursors of eicosanoids related to obesity (prostaglandin E2-PGE2-and leukotriene E4-LTE4). The aim of the present research was to study the lipid profiles, with particular emphasis to LCPUFAs, and the concentrations of eicosanoids PGE2 and LTE4, involved in adipose tissue development, in human milk from overweight mothers compared with normal weight mothers. Materials and Methods: Study including 46 overweight and 86 normal weight breastfeeding volunteers was carried out. Fatty acids and eicosanoids (PGE2 and LTE4) were analyzed in mature human milk. Fatty acids quantification was determined by gas chromatography and mass spectrometry. PGE2 and LTE4 were measured by immununoassay. Results: Human milk of overweight mothers had lower contents of n-3 LCPUFA, including eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA) and higher levels of total n-6 LCPUFA, compared with normal weight mothers (0.45 ± 0.23 versus 0.58 ± 0.38, p = 0.016; 0.05 ± 0.04 versus 0.08 ± 0.08, p = 0.005; 0.26 ± 0.15 versus 0.34 ± 0.22, p = 0.015; 0.84 ± 0.25 versus 0.74 ± 0.20, p = 0.029; respectively). Multiple regression analyses showed that maternal overweight was associated with human milk fatty acid profile. The levels of PGE2 and LTE4 in human milk did not show significant differences between groups. Conclusions: Our findings support the hypothesis that mother weight status influences human milk n-3 LCPUFA lipid composition, but not its relationship with PGE2 and LTE4 levels.
Assuntos
Aleitamento Materno , Desenvolvimento Infantil/fisiologia , Dinoprostona/análise , Ácidos Graxos Ômega-3/metabolismo , Leucotrieno E4/análise , Leite Humano , Obesidade , Adulto , Índice de Massa Corporal , Correlação de Dados , Feminino , Humanos , Recém-Nascido , Leite Humano/química , Leite Humano/fisiologia , Mães/estatística & dados numéricos , Obesidade/diagnóstico , Obesidade/metabolismoRESUMO
Gnaphalium affine is an annual herbaceous plant that is used as a traditional medicine in some Latin American and Asian countries. However, systematic studies on its anti-inflammatory activity and signaling pathways have not yet been reported. In this study, we investigated the anti-inflammatory effect of G. affine methanol extract in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophage cells and fractioned the methanol extract into hexane, chloroform, ethyl acetate (EtOAc), butyl alcohol (BuOH), and distilled water (DW) by measuring the generation of nitric oxide (NO). G. affine inhibited the generation of NO and prostaglandin E2. The chloroform-soluble fraction most effectively inhibited LPS-stimulated NO production. We also examined the cytotoxicity of G. affine in three normal cell lines: RAW264.7, HEK293, and HaCaT. Cell viability assays showed that the methanol extract and chloroform-soluble fraction of G. affine had no cytotoxic effect on normal cell lines. The expression of pro-inflammatory mediators was also investigated. Western blotting and immunofluorescence showed that G. affine reduces the expression of iNOS, COX-2, and MAPKs, as well as activation of NF-κB in LPS-stimulated RAW264.7 cells. RT-PCR showed that G. affine also negatively regulates inflammatory cytokines at the gene expression level. Taken together, G. affine exerts its anti-inflammatory activity through inhibition of NO generation as a result of inhibiting NF-κB and MAPKs-related inflammatory signaling pathways. In addition, the result of GC-MS analysis revealed the presence of nineteen different types of constituents including guaiacol in the chloroform-soluble fraction of G. affine.
Assuntos
Anti-Inflamatórios/farmacologia , Gnaphalium/química , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Compostos Fitoquímicos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Anti-Inflamatórios/química , Western Blotting , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/análise , Ensaio de Imunoadsorção Enzimática , Cromatografia Gasosa-Espectrometria de Massas , Gnaphalium/metabolismo , Células HEK293 , Humanos , Lipopolissacarídeos/toxicidade , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Microscopia de Fluorescência , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , NF-kappa B/antagonistas & inibidores , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Fosforilação/efeitos dos fármacos , Compostos Fitoquímicos/química , Células RAW 264.7 , Reação em Cadeia da Polimerase em Tempo RealRESUMO
BACKGROUND AND OBJECTIVE: This study aimed to assess the effect of multiple sessions of a low-level laser therapy (LLLT) adjuvant to scaling and root planing (SRP) on the treatment of experimental periodontitis (EP) in rats treated with 5-fluorouracil (5-FU). MATERIAL AND METHODS: A total of 120 rats were divided into five groups: no treatment (NT); treatment with 5-FU (60 and 40 mg/kg) and no local periodontal treatment (5FU); treatment with 5-FU and SRP (5FU-SRP); treatment with 5-FU, SRP and one LLLT session (660 nm; 0.035 W; 4.2 J; 120 s) (5FU-SRP-1LLLT); and treatment with 5-FU, SRP and four LLLT sessions (0, 24, 48 and 72 h) (5FU-SRP-4LLLT). EP was induced in the mandibular molars through ligature placement. The alveolar bone loss (ABL) area in the furcation region was analysed histometrically. TRAP, proliferating cell nuclear antigen, RANKL, osteoprotegerin and activated caspase-3 patterns were analysed by immunolabeling. Prostaglandin E2 was quantified using an ELISA, and tumour necrosis factor α and interleukin-6 were assessed using the multiplex method. The prevalence rates of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella nigrescens, Prevotella intermedia and Fusobacterium nucleatum were assessed using the PCR method. The data were subjected to statistical analysis (α = 5%). RESULTS: 5FU, 5FU-SRP and 5FU-SRP-1LLLT treatment groups showed higher ABL compared with the NT group (p < 0.05), whereas the 5FU-SRP-4LLLT group showed lower ABL compared with the 5FU group on day 7 and decreased RANKL immunolabeling (p < 0.05). CONCLUSION: Treatment with 5-FU worsened EP, and multiple LLLT sessions adjuvant to SRP seemed to improve periodontitis in rats subjected to 5-FU chemotherapy.
Assuntos
Tratamento Farmacológico/métodos , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Terapia com Luz de Baixa Intensidade/métodos , Periodontite/terapia , Perda do Osso Alveolar/patologia , Perda do Osso Alveolar/terapia , Animais , Bactérias/isolamento & purificação , Caspase 3/análise , Terapia Combinada , Raspagem Dentária/métodos , Dinoprostona/análise , Inflamação/patologia , Interleucina-6/análise , Masculino , Mandíbula , Dente Molar , Osteoprotegerina/análise , Periodontite/microbiologia , Periodontite/patologia , Ligante RANK/análise , Ratos , Ratos Wistar , Aplainamento Radicular/métodos , Fator de Necrose Tumoral alfa/análiseRESUMO
The aim of the present study was to assess omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) in liver tissue and evaluate changes in the n6-associated inflammatory pathway following liver ischemia/reperfusion (IR) injury. Male Wistar rats which were allowed free access to standard rat chow were included in the study. Blood vessels supplying the median and left lateral hepatic lobes were occluded with an arterial clamp for 60 min, followed by 60 min of reperfusion. Levels of arachidonic acid (AA, C20:4n6), dihomogammalinolenic acid (DGLA, C20:3n6), eicosapentaenoic acid (EPA, C20:5n3) and docosahexaenoic acid (DHA, C22:6n3) in liver tissue were determined by an optimized multiple reaction monitoring method using ultra fastliquid chromatography coupled with tandem mass spectrometry. Phospholipase A2 (PLA2), cyclooxygenase (COX) and prostaglandin E2 (PGE2) were measured in tissue samples to evaluate changes in the n6 inflammatory pathway. Total histopathological score of cellular damage were significantly increased following hepatic IR injury. n3 and n6 PUFA levels were significantly increased in postischemic liver tissue compared to those in nonischemic controls. No significant difference was observed in the AA/DHA and AA/EPA ratio in postischemic liver tissues compared with that in the control. Tissue activity of PLA2 and COX as well as PGE2 levels were significantly increased in postischemic liver tissues compared to those in nonischemic controls. The results of the present study suggested that increased hydrolysis of fatty acids via PLA2 triggers the activity of COX and leads to increased PGE2 levels. Future studies evaluating agents which block the formation of eicosanoids derived from n6 PUFAs may facilitate the development and application of treatment strategies in liver injury following IR.
Assuntos
Ácidos Graxos Ômega-3/análise , Ácidos Graxos Insaturados/análise , Alanina Transaminase/sangue , Animais , Dinoprostona/análise , Isquemia/metabolismo , Isquemia/patologia , Fígado/metabolismo , Fígado/patologia , Masculino , Prostaglandina-Endoperóxido Sintases/metabolismo , Ratos , Ratos Wistar , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
Ulcerative colitis (UC) is a type of inflammatory bowel disease and is considered a chronic gastrointestinal disorder. Igongsan (IGS) is a Korean herbal medicine, which has been used to treat digestive disorders. However, the ameliorative effect and molecular mechanisms of IGS in intestinal inflammation have not yet been studied in detail. The present study aimed to investigate the protective effects of IGS and its constituent, ergosterol, in a mouse model of dextran sulfate sodium (DSS)induced colitis. Colitis was induced in mice by supplementing their drinking water with 5% (w/v) DSS for 7 days. The effects of IGS were then determined on DSSinduced clinical signs of colitis, including weight loss, colon shortening, diarrhea and obscure/gross bleeding. In addition, the effects of IGS were determined on the expression levels of inflammationassociated genes in the colon tissue of DSStreated mice. The results of the present study demonstrated that mice treated with DSS exhibited marked clinical symptoms, including weight loss and reduced colon length. Treatment with IGS attenuated these symptoms and also suppressed the expression levels of tumor necrosis factorα and interleukin6, as well as the expression of cyclooxygenase2 in the colon tissue of DSStreated mice. IGS also reduced the activation of the transcription factor nuclear factorκB p65 in the colon tissue of DSStreated mice. In addition, ergosterol was shown to attenuate the DSSinduced clinical symptoms of colitis in mice. In conclusion, the present study provided experimental evidence that IGS may be a useful therapeutic drug for patients with UC.
Assuntos
Anti-Inflamatórios/uso terapêutico , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colo/efeitos dos fármacos , Sulfato de Dextrana , Ergosterol/uso terapêutico , Animais , Anti-Inflamatórios/química , Colite/imunologia , Colite/patologia , Colo/imunologia , Colo/patologia , Ciclo-Oxigenase 2/análise , Ciclo-Oxigenase 2/imunologia , Dinoprostona/análise , Dinoprostona/imunologia , Ergosterol/química , Feminino , Interleucina-6/análise , Interleucina-6/imunologia , Medicina Tradicional Coreana , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/análise , NF-kappa B/imunologia , Plantas Medicinais/química , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/imunologiaRESUMO
The objective of the present study was to find the optimum dose of flaxseed that would decrease PG and alter oestrogen pathway endpoints implicated in ovarian cancer. In the study, four groups of fifty 1.5-year-old chickens were fed different amounts of flaxseed (0, 5, 10 or 15% of their total diet) for 4 months and were then killed to collect blood and tissues. Levels of flaxseed lignan metabolites, Enterolactone (EL) and Enterodiol (ED) were measured in the serum, liver and ovaries by liquid chromatography-MS/MS, and n-3 and n-6 fatty acid (FA) levels were measured by GC. The effects of the varied flaxseed doses were assessed by measuring levels of PGE2 and oestrogen metabolites (16-hydroxyestrone (16-OHE1) and 2-hydroxyestrone (2-OHE1)) as well as by analysing the expression of the oestradiol metabolising enzymes CYP3A4 (cytochrome p450, family 3, subfamily A, polypeptide 4), CYP1B1 (cytochrome p450, family 1, subfamily B, polypeptide 1) and CYP1A1 (cytochrome p450, family 1, subfamily A, polypeptide 1) and that of oestrogen receptor α (ERα) in the ovaries. The ratio of n-3:n-FA increased with an increase in flaxseed supplementation and corresponded to a dose-dependent decrease in cyclo-oxygenase-2 protein and PGE2 levels. EL and ED increased in the serum, liver and ovaries with increased concentrations of flaxseed. Flaxseed decreased the expression of ERα in the ovaries. The ratio of 2-OHE1:16-OHE1 in the serum increased significantly in the 15% flaxseed diet, and there was a corresponding increase in CYP1A1 in the liver and decrease in CYP3A4 in the ovaries. CYP1B1 mRNA also decreased with flaxseed diet in the ovaries. The 15% flaxseed-supplemented diet significantly decreased inflammatory PGE2, ERα, CYP3A4, CYP1B1 and 16-OHE1, but it increased CYP1A1 and 2-OHE1, which thus reduced the inflammatory and pro-carcinogenic micro-environment of the ovaries.
Assuntos
Anticarcinógenos/administração & dosagem , Galinhas , Dieta/veterinária , Linho , Neoplasias Ovarianas/prevenção & controle , Ovário/metabolismo , 4-Butirolactona/análogos & derivados , 4-Butirolactona/análise , 4-Butirolactona/sangue , Animais , Ciclo-Oxigenase 1/análise , Ciclo-Oxigenase 1/genética , Ciclo-Oxigenase 2/análise , Ciclo-Oxigenase 2/genética , Citocromo P-450 CYP1A1/análise , Citocromo P-450 CYP1B1/análise , Citocromo P-450 CYP3A/análise , Suplementos Nutricionais , Dinoprostona/análise , Receptor alfa de Estrogênio/análise , Estrogênios/metabolismo , Ácidos Graxos Ômega-3/análise , Ácidos Graxos Ômega-6/análise , Feminino , Hidroxiestronas/análise , Lignanas/análise , Lignanas/sangue , Lignanas/metabolismo , Fígado/química , Ovário/química , RNA Mensageiro/análiseRESUMO
BACKGROUND: Sodium metabisulfite is commonly used as preservative in foods but can oxidize to sulfite radicals initiating molecular oxidation. Ghrelin is a peptide hormone primarily produced in the stomach and has anti-inflammatory effects in many organs. This study aimed to assess endogenous omega-3 (n-3) and omega-6 (n-6) polyunsaturated fatty acids (PUFAs) in rat peripheral organs following sodium metabisulfite treatment and determine the possible effect of ghrelin on changes in n-6 inflammatory pathway. METHODS: Male Wistar rats included in the study were allowed free access to standard rat chow. Sodium metabisulfite was given by gastric gavage and ghrelin was administered intraperitoneally for 5 weeks. Levels of arachidonic acid (AA, C20:4n-6), dihomo-gamma-linolenic acid (DGLA, C20:3n-6), eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C22:6n-3) in liver, heart and kidney tissues were determined by an optimized multiple reaction monitoring (MRM) method using ultra fast-liquid chromatography (UFLC) coupled with tandem mass spectrometry (MS/MS). Cyclooxygenase (COX) and prostaglandin E2 (PGE2) were measured in tissue samples to evaluate changes in n-6 inflammatory pathway. RESULTS: Omega-6 PUFA levels, AA/DHA and AA/EPA ratio were significantly increased in liver tissue following sodium metabisulfite treatment compared to controls. No significant change was observed in heart and kidney PUFA levels. Tissue activity of COX and PGE2 levels were also significantly increased in liver tissue of sodium metabisulfite treated rats compared to controls. Ghrelin treatment decreased n-6 PUFA levels and reduced COX and PGE2 levels in liver tissue of sodium metabisulfite treated rats. CONCLUSION: Current results suggest that ghrelin exerts anti-inflammatory action through modulation of n-6 PUFA levels in hepatic tissue.
Assuntos
Ácidos Graxos Ômega-6/biossíntese , Grelina/farmacologia , Inflamação/metabolismo , Fígado/efeitos dos fármacos , Sulfitos/farmacologia , Ácido 8,11,14-Eicosatrienoico/análise , Animais , Ácido Araquidônico/análise , Dinoprostona/análise , Ácidos Docosa-Hexaenoicos/análise , Ácido Eicosapentaenoico/análise , Ácidos Graxos Ômega-3/análise , Ácidos Graxos Ômega-3/biossíntese , Ácidos Graxos Ômega-6/análise , Rim/química , Fígado/metabolismo , Masculino , Miocárdio/química , Prostaglandina-Endoperóxido Sintases/análise , Ratos , Ratos Wistar , Espectrometria de Massas por Ionização por Electrospray , Sulfitos/antagonistas & inibidoresRESUMO
BACKGROUND: Lung contusion, which can occur in patients with blunt thoracic trauma, is a leading risk factor for development of acute lung injury (ALI) and acute respiratory distress syndrome. Statins are lipid-lowering drugs with many beneficial antiinflammatory and antioxidative effects. We therefore hypothesized that the administration of statins immediately after trauma will inhibit the production of inflammatory mediators, and thereby alleviate the severity of lung injury. METHODS: A model of blunt chest injury in rat was employed. The effects of statins (rosuvastatin) and cyclooxygenase-2 (COX-2) inhibitors (meloxicam) on ALI were assessed by measuring inflammatory mediator levels in the serum and in the bronchoalveolar space. Animals were killed at the end of day 3. Histologic evaluation of lung tissue was performed to confirm the presence and severity of lung contusion as well as the effects of statins, nonsteroidal antiinflammatory drugs, and their combination. RESULTS: Administration of meloxicam after lung contusion decreased the amount of neutrophil infiltration; however, marked hemorrhage and edema were still noticed. Administration of rosuvastatin decreased significantly cytokine levels that were increased after the blunt chest trauma. Rosuvastatin increased the expression of inducible nitric oxide (iNOS), COX-2, heme oxygenase-1 (HO-1), and prostaglandin E2 (PGE-2) in the bronchoalveolar lavage fluid of the rat contused lungs. Coadministration of meloxicam prevented these changes. CONCLUSION: Rosuvastatin treatment after lung contusion attenuated several features of ALI. The enhanced activity of iNOS, COX-2, and HO-1 in the lung may reflect the advent of protective processes that took place in the contused lung. To our knowledge, this is the first demonstration that prostaglandin pathways play an essential role in the effects of statins in lung injury.
Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Fluorbenzenos/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/patologia , Animais , Líquido da Lavagem Broncoalveolar/química , Contusões/complicações , Ciclo-Oxigenase 2/análise , Dinoprostona/análise , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Fluorbenzenos/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Pulmão/patologia , Masculino , Meloxicam , Pirimidinas/farmacologia , Distribuição Aleatória , Ratos , Rosuvastatina Cálcica , Sulfonamidas/farmacologia , Tiazinas , TiazóisRESUMO
Inflammation and the presence of pro-inflammatory cytokines are associated with numerous chronic diseases such as type-2 diabetes mellitus, cardiovascular disease, Alzheimer's disease, and cancer. An overwhelming amount of data indicates that curcumin, a polyphenol obtained from the Indian spice turmeric, Curcuma longa, is a potential chemopreventive agent for treating certain cancers and other chronic inflammatory diseases. However, the low bioavailability of curcumin, partly due to its low solubility and stability in the digestive tract, limits its therapeutic applications. Recent studies have demonstrated increased bioavailability and health-promoting effects of a novel solid lipid particle formulation of curcumin (Curcumin SLCP, Longvida(®)). The goal of this study was to evaluate the aqueous solubility and in vitro anti-inflammatory effects of solid lipid curcumin particle (SLCP) formulations using lipopolysaccharide (LPS)-stimulated RAW 264.7 cultured murine macrophages. SLCPs treatment significantly decreased nitric oxide (NO) and prostaglandin-E2 (PGE2) levels at concentrations ranging from 10 to 50 µg/mL, and reduced interleukin-6 (IL-6) levels in a concentration-dependent manner. Transient transfection experiments using a nuclear factor-kappa B (NF-κB) reporter construct indicate that SLCPs significantly inhibit the transcriptional activity of NF-κB in macrophages. Taken together, these results show that in RAW 264.7 murine macrophages, SLCPs have improved solubility over unformulated curcumin, and significantly decrease the LPS-induced pro-inflammatory mediators NO, PGE2, and IL-6 by inhibiting the activation of NF-κB.
Assuntos
Anti-Inflamatórios/farmacologia , Curcumina/farmacologia , Lipídeos , Animais , Disponibilidade Biológica , Química Farmacêutica , Curcumina/química , Curcumina/farmacocinética , Dinoprostona/análise , Mediadores da Inflamação/antagonistas & inibidores , Interleucina-6/análise , Lipopolissacarídeos/farmacologia , Macrófagos/química , Macrófagos/efeitos dos fármacos , Camundongos , NF-kappa B/antagonistas & inibidores , Óxido Nítrico/análise , Células RAW 264.7 , Solubilidade , ÁguaRESUMO
BACKGROUND: In vitro fertilisation (IVF) treatment provides an opportunity to study early developmental responses to periconceptional dietary interventions. Retrospective studies have suggested links between preconception diet and fertility, and more recently, a "Mediterranean" diet has been reported to increase pregnancy rates by up to 40%. In addition, a prospective study examining increased intake of omega-3 polyunsaturated fats demonstrated a quickened rate of embryo development after IVF. However, up to now, few prospective randomised controlled trials have investigated the impact of periconceptional dietary interventions on fertility outcomes. METHODS AND DESIGN: The study is a randomised controlled trial of a dietary intervention consisting of olive oil for cooking, an olive oil based spread, and a daily supplement drink enriched with Vitamin D (10 microgram daily) and marine omega-3 fatty acids (2 g daily) for 6 weeks preconception versus a control diet of sunflower seed oil for cooking, a sunflower oil based spread, and a daily supplement drink without added Vitamin D or marine omega-3 fatty acids. Couples undergoing IVF will be randomised to either the intervention or control group (55 in each arm). The primary endpoint is embryo developmental competency in vitro, measured by validated morphokinetic markers. Secondary outcomes will include the effect of the dietary intervention on the nutritional content of the intrauterine environment. DISCUSSION: This approach will enable rigorous examination of the impact of the dietary intervention on early embryo development, together with the influence of the peri-implantation intra-uterine nutritional environment. TRIAL REGISTRATION: ISRCTN50956936.
Assuntos
Dieta , Suplementos Nutricionais , Desenvolvimento Embrionário/efeitos dos fármacos , Fertilização in vitro/métodos , Cuidado Pré-Concepcional , Adolescente , Adulto , Culinária , Dinoprosta/análise , Dinoprostona/análise , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Docosa-Hexaenoicos/análise , Ácido Eicosapentaenoico/administração & dosagem , Ácido Eicosapentaenoico/análise , Endométrio/química , Endométrio/citologia , Endométrio/imunologia , Feminino , Ácido Fólico/análise , Líquido Folicular/química , Humanos , Masculino , Azeite de Oliva , Óleos de Plantas/administração & dosagem , Gravidez , Taxa de Gravidez , Projetos de Pesquisa , Análise do Sêmen , Óleo de Girassol , Vitamina B 12/análise , Vitamina B 6/análise , Vitamina D/administração & dosagem , Vitamina D/análise , Adulto JovemRESUMO
BACKGROUND: Despite Cryptostegia grandiflora Roxb. ex R. Br. (Apocynaceae) leaves are widely used in folk Caribbean Colombian medicine for their anti-inflammatory effects, there are no studies that support this traditional use. Therefore, this work aimed to evaluate the effect of the total extract and primary fractions obtained from Cryptostegia grandiflora leaves, using in vivo and in vitro models of inflammation, and further get new insights on the mechanisms involved in this activity. RESULTS: Ethanolic extract of Cryptostegia grandiflora leaves, and its corresponding ether and dichloromethane fractions, significantly reduced inflammation and myeloperoxidase activity (MPO) in ear tissue of mice treated with 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Histological analysis revealed a reduction of edema and leukocyte infiltration. Complementarily, we demonstrated that extract and fractions reduced nitric oxide (NOâ¢) and prostaglandin E2 (PGE2) production in LPS-stimulated RAW 264.7 macrophages, as well as scavenging activity on DPPH and ABTS radicals. CONCLUSIONS: Our results demonstrated for the first time the anti-inflammatory activity of Cryptostegia grandiflora leaves, supporting its traditional use. This activity was related to inhibition of MPO activity, and PGE2 and NO⢠production. These mechanisms and its antioxidant activity could contribute, at least in part, to the anti-inflammatory effect showed by this plant.
Assuntos
Anti-Inflamatórios/farmacologia , Apocynaceae/química , Edema/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Animais , Linhagem Celular Tumoral/efeitos dos fármacos , Citotoxinas/farmacologia , Dinoprostona/análise , Feminino , Inflamação/tratamento farmacológico , Camundongos Endogâmicos ICR , Óxido Nítrico/análise , Ocitócicos/análise , Peroxidase/antagonistas & inibidores , Folhas de Planta/químicaRESUMO
Malva sylvestris is a species used worldwide as an alternative to anti-inflammatory therapies; however, its mechanism of action remains unknown. In this paper, the anti-inflammatory effects of M. sylvestris alcoholic extracts were evaluated by measuring the pro-inflammatory mediators PGE2 and PGD2 in desferrioxamine-stimulated phorbol 12-myristate 13-acetate-differentiated U937 cells. An HPLC-DAD fingerprint of the M. sylvestris extract was performed and caffeic acid, ferulic acid and scopoletin were identified and quantified. An HPLC-MS/MS method was developed and validated to separate and measure the prostaglandins. The lower limits of detection (~0.5 ng/mL for PGE2 and PGD2) and quantification (1.0 ng/mL for PGE2 and PGD2) indicated that the method is highly sensitive. The calibration curves showed excellent coefficients of correlation (r > 0.99) over the range of 1.0-500.0 ng/mL, and at different levels, the accuracy ranged from 96.4 to 106.4% with an RSD < 10.0% for the precision study. This method was successfully applied using U937-d cells. A significant dose-dependent reduction of PGE2 and PGD2 levels occurred using 10 µg/mL (10.74 ± 2.86 and 9.60 ± 6.89%) and 50 µg/mL of extract (48.37 ± 3.24 and 53.06 ± 6.15%), suggesting that the anti-inflammatory mechanisms evoked by M. sylvestris may be related to modulation of these mediators.
Assuntos
Anti-Inflamatórios/farmacologia , Dinoprostona/análise , Extratos Vegetais/farmacologia , Prostaglandina D2/análise , Anti-Inflamatórios/química , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida/métodos , Desferroxamina/farmacologia , Dinoprostona/metabolismo , Humanos , Limite de Detecção , Modelos Lineares , Malva , Extratos Vegetais/química , Prostaglandina D2/metabolismo , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos , Células U937RESUMO
BACKGROUND: Ligularia fischeri (common name Gomchwi) is known for its pharmaceutical properties and used in the treatment of jaundice, scarlet-fever, rheumatoidal arthritis, and hepatic diseases; however, little is known about its anti-inflammatory effect. In this study the influence of blanching and pan-frying on the anti-inflammatory activity of Ligularia fischeri (LF) was evaluated. RESULTS: Fresh LF and cooked LF showed no significant effect on the viability of macrophages after 24 h incubation. Fresh LF was found to be the most potent inhibitor of nitric oxide (NO) production at 100 µg/ml, while pan-fried LF showed little inhibitory effect on lipoloysaccharide (LPS) stimulated murine machrophage RAW264.7 cells. In contrast with its effect on NO production, pan-fried LF showed significant attenuation of the expression of inducible nitiric oxide synthase (iNOS) compared with fresh LF. In the cooking method of LF, PGE2 production was not affected in the LPS-induced RAW 264.7 cells. In LPS-induced RAW 264.7 cells, pretreatment by fresh and cooked LF increased COX2 mRNA expression. The 3-O-caffeoylquinic acid content of blanching and pan-frying LF increased by 4.92 and 9.7 fold with blanching and pan-frying respectively in comparison with uncooked LF. CONCLUSIONS: Regardless of the cooking method, Ligularia fischeri exhibited potent inhibition of NO production through expression of iNOS in LPS-induced RAW264.7 cells.
Assuntos
Asteraceae/química , Culinária/métodos , Macrófagos/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico/biossíntese , Preparações de Plantas/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Asteraceae/classificação , Sobrevivência Celular , Cromatografia Líquida de Alta Pressão , Ciclo-Oxigenase 2/análise , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/análise , Dinoprostona/biossíntese , Temperatura Alta , Lipopolissacarídeos , Macrófagos/fisiologia , Camundongos , Ácido Quínico/análogos & derivados , Ácido Quínico/análise , Ácido Quínico/classificação , Células RAW 264.7 , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismoRESUMO
BACKGROUND: Despite Cryptostegia grandiflora Roxb. ex R. Br. (Apocynaceae) leaves are widely used in folk Caribbean Colombian medicine for their anti-inflammatory effects, there are no studies that support this traditional use. Therefore, this work aimed to evaluate the effect of the total extract and primary fractions obtained from Cryptostegia grandiflora leaves, using in vivo and in vitromodels of inflammation, and further get new insights on the mechanisms involved in this activity. RESULTS: Ethanolic extract of Cryptostegia grandiflora leaves, and its corresponding ether and dichloromethane fractions, significantly reduced inflammation and myeloperoxidase activity (MPO) in ear tissue of mice treated with 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Histological analysis revealed a reduction of edema and leukocyte infiltration. Complementarily, we demonstrated that extract and fractions reduced nitric oxide (NOâ¢) and prostaglandin E2 (PGE2) production in LPS-stimulated RAW 264.7 macrophages, as well as scavenging activity on DPPH and ABTS radicals. CONCLUSIONS: Our results demonstrated for the first time the anti-inflammatory activity of Cryptostegia grandiflora leaves, supporting its traditional use. This activity was related to inhibition of MPO activity, and PGE2 and NO⢠production. These mechanisms and its antioxidant activity could contribute, at least in part, to the anti-inflammatory effect showed by this plant.
Assuntos
Animais , Feminino , Camundongos , Extratos Vegetais/uso terapêutico , Apocynaceae/química , Edema/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Ocitócicos/análise , Dinoprostona/análise , Peroxidase/antagonistas & inibidores , Folhas de Planta/química , Citotoxinas/farmacologia , Linhagem Celular Tumoral/efeitos dos fármacos , Inflamação/tratamento farmacológico , Camundongos Endogâmicos ICR , Óxido Nítrico/análiseRESUMO
BACKGROUND: Ligularia fischeri (common name Gomchwi) is known for its pharmaceutical properties and used in the treatment of jaundice, scarlet-fever, rheumatoidal arthritis, and hepatic diseases; however, little is known about its anti-inflammatory effect. In this study the influence of blanching and pan-frying on the anti-inflammatory activity of Ligularia fischeri (LF) was evaluated. RESULTS: Fresh LF and cooked LF showed no significant effect on the viability of macrophages after 24 h incubation. Fresh LF was found to be the most potent inhibitor of nitric oxide (NO) production at 100 µg/ml, while pan-fried LF showed little inhibitory effect on lipoloysaccharide (LPS) stimulated murine machrophage RAW264.7 cells. In contrast with its effect on NO production, pan-fried LF showed significant attenuation of the expression of inducible nitiric oxide synthase (iNOS) compared with fresh LF. In the cooking method of LF, PGE2 production was not affected in the LPS-induced RAW 264.7 cells. In LPS-induced RAW 264.7 cells, pretreatment by fresh and cooked LF increased COX2 mRNA expression. The 3-O-caffeoylquinic acid content of blanching and pan-frying LF increased by 4.92 and 9.7 fold with blanching and pan-frying respectively in comparison with uncooked LF. CONCLUSIONS: Regardless of the cooking method, Ligularia fischeri exhibited potent inhibition of NO production through expression of iNOS in LPS-induced RAW264.7 cells.
Assuntos
Animais , Camundongos , Culinária/métodos , Asteraceae/química , Preparações de Plantas/farmacologia , Óxido Nítrico Sintase Tipo II/metabolismo , Macrófagos/efeitos dos fármacos , Óxido Nítrico/biossíntese , Ácido Quínico/análise , Ácido Quínico/análogos & derivados , Ácido Quínico/classificação , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Dinoprostona/análise , Dinoprostona/biossíntese , Sobrevivência Celular , Lipopolissacarídeos , Cromatografia Líquida de Alta Pressão , Asteraceae/classificação , Ciclo-Oxigenase 2/análise , Ciclo-Oxigenase 2/metabolismo , Células RAW 264.7 , Temperatura Alta , Macrófagos/fisiologia , Anti-Inflamatórios/farmacologiaRESUMO
There is evidence that vitamin E (VE) has anti-inflammatory and analgesic properties in human osteoarthritis (OA). This double-blinded and randomized pilot study used a broad spectrum of clinical and laboratory parameters to investigate whether such beneficial effects could be detected in a canine experimental OA model. Dogs were divided into 2 groups: control (n = 8), which received a placebo, and test group (n = 7), which received 400 IU/animal per day of VE for 55 d, starting the day after transection of the cranial cruciate ligament. Lameness and pain were assessed using a visual analogue scale (VAS), numerical rating scale (NRS), and electrodermal activity (EDA) at day 0, day 28, and day 55. Cartilage and synovial inflammation lesions were assessed. One-side comparison was conducted at an alpha-threshold of 10%. At day 56, dogs were euthanized and concentrations of prostaglandin E2 (PGE2), nitrogen oxides (NOx), and interleukin-1 beta (IL-1ß) were measured in synovial fluid. Concentrations of NOx and PGE2 in synovial fluid were lower in the test group (P < 0.0001 and P = 0.03, respectively). Values of VAS, NRS, and EDA showed a consistent trend to be lower in the test group than in the control, while statistical significance was reached for VAS at day 55 and for EDA at day 28 (adjusted P = 0.07 in both cases). Histological analyses of cartilage showed a significant reduction in the scores of lesions in the test group. This is the first time that a study in dogs with OA using a supplement with a high dose of vitamin E showed a reduction in inflammation joint markers and histological expression, as well as a trend to improving signs of pain.
La vitamine E (VE) est connue par ses propriétés anti-inflammatoires et analgésiques dans le traitement de l'ostéoarthrose (OA) chez l'humain. Dans notre étude pilote nous avons utilisé un ensemble de paramètres cliniques et de laboratoire afin de déterminer si ces effets bénéfiques de la VE pourront être détectés chez le chien arthrosique, dans un modèle expérimental d'OA. Les chiens utilisés ont été divisés en 2 groupes: témoin (n = 8), qui a reçu un placebo et un groupe supplémenté (n = 7), qui a reçu 400 UI de VE/animal/jour pendant 55 jours, la supplémentation orale a commencé un jour après la section du ligament croisé crânial. Avant la chirurgie (J0), J28 et J55 après chirurgie, la boiterie et la douleur ont été évaluées à l'aide d'une échelle visuelle analogique (EVA), d'une échelle d'évaluation numérique (NRS), et par la mesure de l'activité électrodermique (EDA). Les lésions au niveau du cartilage et l'inflammation synoviale ont été évalués. Une seule comparaison statistique a été réalisée avec un seuil alpha à 10 %. Au jour 56, les chiens ont été euthanasiés et les concentrations de prostaglandine E2 (PGE2), d'oxyde d'azote (NOx) et d'interleukine-1 bêta (IL-1ß) ont été mesurées dans le liquide synovial. Les concentrations synoviales de NOx et de PGE2 étaient plus faibles dans le groupe traité (P < 0,0001 et P = 0,03, respectivement). Les valeurs de l'EVA, de NRS et de l'EDA ont montré une tendance constante à être plus faible dans le groupe traité par comparaison au groupe témoin, avec un effet significatif de la VE qui a été observé pour VAS au jour 55 et EDA au jour 28 (P ajustée = 0,07 dans les deux cas). Les analyses histologiques du cartilage ont montré une réduction significative des scores lésionnels chez le groupe traité. Cette étude est la première à démontrer qu'une supplémentation orale avec une dose élevée de VE chez des chiens arthrosiques permet de réduire la libération des marqueurs inflammatoires et les lésions histologiques au niveau du cartilage, ainsi qu'une tendance à améliorer les signes de douleur.(Traduit par Docteur Serge Messier).
Assuntos
Ligamento Cruzado Anterior/imunologia , Doenças do Cão/imunologia , Inflamação/veterinária , Coxeadura Animal/imunologia , Osteoartrite/veterinária , Vitamina E/farmacologia , Animais , Ligamento Cruzado Anterior/patologia , Antioxidantes/administração & dosagem , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Dinoprostona/análise , Doenças do Cão/tratamento farmacológico , Doenças do Cão/patologia , Cães , Método Duplo-Cego , Histocitoquímica/veterinária , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/patologia , Interleucina-1beta/análise , Coxeadura Animal/tratamento farmacológico , Coxeadura Animal/patologia , Óxidos de Nitrogênio/análise , Osteoartrite/tratamento farmacológico , Osteoartrite/imunologia , Osteoartrite/patologia , Dor/tratamento farmacológico , Dor/veterinária , Projetos Piloto , Distribuição Aleatória , Líquido Sinovial/química , Líquido Sinovial/imunologia , Vitamina E/administração & dosagem , Vitamina E/uso terapêuticoRESUMO
OBJECTIVES: Piperine, a main component of Piper species, is a plant alkaloid with a long history of medical use in a variety of inflammatory disorders like rheumatoid arthritis. Due to side effects in current treatment modalities of rheumatoid arthritis, the interest in alternative, well tolerated anti-inflammatory remedies has re-emerged. The aim of this work was to evaluate the anti-inflammatory and antiarthritic effects of piperine. METHODS: Arthritis was induced in male Wistar rats by collagen induced arthritis (CIA) method. Piperine was administered at a dose of 100mgkg(-1) and indomethacin at 1mgkg(-1) body weight once daily for 21days. The effects of treatment in the rats were assessed by biochemical (articular elastase, MPO, LPO, GSH, Catalase, SOD and NO), inflammatory mediators (IL-1ß, TNF-α, IL-10 and PGE2) and histological studies in joints. RESULTS: Piperine was effective in bringing significant changes on all the parameters (articular elastase, MPO, LPO, GSH, Catalase, SOD and NO) studied. Oral administration of piperine resulted in significantly reduced the levels of pro-inflammatory mediators (IL-1ß, TNF-α and PGE2) and increased level of IL-10. The protective effects of piperine against RA were also evident from the decrease in arthritis scoring and bone histology. CONCLUSIONS: In conclusion, the fact that piperine alter a number of factors known to be involved in RA pathogenesis indicates that piperine can be used similar to indomethacin as a safe and effective therapy for CIA and may be useful in the treatment of rheumatoid arthritis.