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1.
Z Naturforsch C J Biosci ; 65(9-10): 551-61, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21138055

RESUMO

Physicochemical characterization and antinociceptive and anti-inflammatory activities of atranorin (AT) extracted from Cladina kalbii Ahti in formalin- and capsaicin-induced orofacial pain and anti-inflammatory tests in rodents were studied. Physicochemical characterization showed that AT has the general formula C19H18O8. Male Swiss mice were pretreated with AT (100, 200, and 400 mg/kg, i.p.), morphine (3 mg/kg, i.p.), or vehicle (0.9% saline with two drops of 0.2% Tween 80) before formalin (20 microl, 2%) or capsaicin (20 microl, 2.5 microg) were injected into the right vibrissa. Our results showed that i.p. treatment with AT displayed marked inhibitory effects in different orofacial pain tests in mice. AT (400 mg/kg, i.p.) was effective in reducing the nociceptive face-rubbing behavioural response in both phases of the formalin test, which was also naloxone-sensitive. Additionally, AT produced a significant antinociceptive effect at all doses in the capsaicin test. Such results were unlikely to be provoked by motor abnormality, since AT-treated mice exhibited no performance alteration on the rota rod apparatus. AT exhibited significant anti-inflammatory activity in the acute model of inflammation (leukocyte migration to the peritoneal cavity), carrageenan- and arachidonic acid-induced hind paw edema in rats. Additionally, AT exhibited a dose-dependent antioxidant activity in vitro, as assessed by total radical-trapping antioxidant parameter and total antioxidant reactivity assays. All these findings suggest that AT might represent an important tool for the management of orofacial pain and/or inflammatory disorders.


Assuntos
Hidroxibenzoatos/farmacologia , Medição da Dor/efeitos dos fármacos , Dor/tratamento farmacológico , Alérgenos/farmacologia , Animais , Carragenina , Edema/induzido quimicamente , Edema/tratamento farmacológico , Dor Facial/induzido quimicamente , Dor Facial/tratamento farmacológico , Hidroxibenzoatos/química , Hidroxibenzoatos/uso terapêutico , Hipnóticos e Sedativos/farmacologia , Masculino , Camundongos , Morfina/farmacologia , Morfina/uso terapêutico , Fármacos Neuromusculares Despolarizantes/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Teste de Desempenho do Rota-Rod
2.
Exp Lung Res ; 35(5): 427-38, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19842843

RESUMO

Lungs require an adequate supply of vitamin A for normal embryonic development, postnatal maturation, and maintenance and repair during adult life. However, recent intervention studies revealed that supplementation with retinoids resulted in a higher incidence of lung cancer, although the mechanisms underlying this effect are still unknown. Here, the authors studied the effect of vitamin A supplementation on oxidative stress parameters in lungs of Wistar rats. Vitamin A supplementation either at therapeutic (1000 and 2500 IU/kg) or excessive (4500 and 9000 IU/kg) doses for 28 days induced lipid peroxidation, protein carbonylation, and oxidation of protein thiol groups, as well as change in catalase (EC 1.11.1.6; CAT) and superoxide dismutase (EC 1.15.1.1, SOD) activities and immunocontents. These results altogether suggest that vitamin A supplementation causes significant changes in redox balance the free radical status in lungs, which are frequently associated to severe lung dysfunction.


Assuntos
Catalase/metabolismo , Suplementos Nutricionais , Pulmão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Vitamina A/farmacologia , Animais , Suplementos Nutricionais/toxicidade , Relação Dose-Resposta a Droga , Immunoblotting , Peroxidação de Lipídeos/efeitos dos fármacos , Pulmão/enzimologia , Masculino , Oxirredução , Carbonilação Proteica/efeitos dos fármacos , Ratos , Ratos Wistar , Compostos de Sulfidrila/metabolismo , Vitamina A/toxicidade
3.
J Food Drug Anal ; 23(3): 387-398, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28911695

RESUMO

The purpose of this study was to evaluate the bioactive compounds and antioxidant activity of extracts from araçá (Psidium cattleianum), butiá (Butia eriospatha), and pitanga (Eugenia uniflora) fruits with different flesh colors (i.e., purple, red, and orange), and blackberries (Rubus sp.; cv. Xavante and Cherokee) collected in the southern region of Brazil. The content of ascorbic acid, total carotenoids, and phenolics were determined. The profile of the phenolic compounds was assessed by high-performance liquid chromatography combined with diode array detection (HPLC-DAD). The antioxidant activity was determined using the ferric-reducing antioxidant power (FRAP) assay, 2,2-diphenyl-2-picrylhydrazyl hydrate (DPPH) assay, total reactive antioxidant potential (TRAP) assay, and total antioxidant reactivity (TAR) assay. The Xavante blackberry and purple-fleshed pitanga showed the highest total phenolic content [816.50 mg gallic acid equivalents (GAE)/100g and 799.80 mg GAE/100g, respectively]. The araçá and red-fleshed pitanga showed the highest carotenoid content (6.27 ug ß-carotene/g and 5.86 ug ß-carotene/g, respectively). The fruits contained several phenolic compounds such as quercetin derivatives, quercitrin, isoquercitrin, and cyanidin derivatives, which may contribute differentially to the antioxidant capacity. The highest scavenging activity in the DPPH assay was found for purple-fleshed pitanga (IC50 36.78 mg/L), blackberries [IC50 44.70 (Xavante) and IC50 78.25 mg/L (Cherokee)], and araçá (IC50 48.05 mg/L), which also showed the highest FRAP, followed by orange- and red-fleshed pitanga. Our results revealed that some fruits grown in southern Brazil such as purple-fleshed pitanga, blackberries, and araçá are rich sources of phenolic compounds and have great antioxidant activity.

4.
J Cancer Res Clin Oncol ; 140(3): 461-70, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24449404

RESUMO

PURPOSE: The expression levels of human antioxidant genes (HAGs) and oxidative markers were investigated in light of lung adenocarcinoma aggressiveness and patient outcome. METHODS: We assayed in vitro the tumoral invasiveness and multidrug resistance in human lung adenocarcinoma (AdC) cell lines (EKVX and A549). Data were associated with several redox parameters and differential expression levels of HAG network. The clinicopathological significance of these findings was investigated using microarray analysis of tumor tissue and by immunohistochemistry in archival collection of biopsies. RESULTS: An overall increased activity (expression) of selected HAG components in the most aggressive cell line (EKVX cells) was observed by bootstrap and gene set enrichment analysis (GSEA). In vitro validation of oxidative markers revealed that EKVX cells had high levels of oxidative stress markers. In AdC cohorts, GSEA of microarray datasets showed significantly high levels of HAG components in lung AdC samples in comparison with normal tissue, in advanced stage compared with early stage and in patients with poor outcome. Cox multivariate regression analysis in a cohort of early pathologic (p)-stage of AdC cases showed that patients with moderate levels of 4-hydroxynonenal, a specific and stable end product of lipid peroxidation, had a significantly less survival rate (hazard ratio of 8.87) (P < 0.05). CONCLUSIONS: High levels of oxidative markers are related to tumor aggressiveness and can predict poor outcome of early-stage lung adenocarcinoma patients.


Assuntos
Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Aldeídos/metabolismo , Antioxidantes/metabolismo , Peroxidação de Lipídeos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma de Pulmão , Adulto , Idoso , Linhagem Celular Tumoral , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Estadiamento de Neoplasias , Razão de Chances , Oxirredução , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos
5.
Acta Neuropsychiatr ; 24(2): 101-8, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26952951

RESUMO

OBJECTIVE: Vitamin A is a redox-active molecule and its inadvertent utilisation as a preventive therapy against ageing or neurodegeneration has become a harmful habit among humans at different ages. Mitochondrial dysfunction and redox impairment may be induced by vitamin A supplementation experimentally. Nonetheless, it is still not clear by which mechanisms vitamin A elicits such effects. Then, we performed this investigation to analyse whether mitochondria isolated from frontal cortex and hippocampus of vitamin A-treated rats are more sensitive to a challenge with amyloid-ß (Aß) peptides 1-40 or 1-42. METHODS: Adult Wistar rats received vitamin A at 1000-9000 IU/kg/day orally for 28 days. Then, mitochondria were isolated and the challenge with Aß peptides 1-40 or 1-42 (at 0.2 or 0.1 µM, respectively) for 10 min was carried out before mitochondrial electron transfer chain enzyme activity, superoxide anion radical (O2 -•) production and 3-nitrotyrosine content quantification. RESULTS: Mitochondria obtained from vitamin A-treated rats are more sensitive to Aß peptides 1-40 or 1-42 than mitochondria isolated from the control group, as decreased mitochondrial complex enzyme activity and increased O2 -• production and 3-nitrotyrosine content were observed in incubated mitochondria isolated from vitamin A-treated rats. CONCLUSION: These data suggest that oral intake of vitamin A at clinical doses increases the susceptibility of mitochondria to a neurotoxic agent even at low concentrations.

6.
Free Radic Res ; 44(5): 505-12, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20402601

RESUMO

The aim of the present study was to compare electrons flux and oxidative/nitrosative stress parameters on the heart among rats supplemented with vitamin A and one not supplemented long-term. Vitamin A has important roles for the cardiovascular system as well as antioxidant properties. However, pro-oxidant properties have been reported. Male adult rats were treated with four different doses of retinyl palmitate (1000-9000 IU/Kg/day) or saline (control) for 28 days and the heart was removed for analysis. Electrons flux and oxidative/nitrosative stress parameters were evaluated and statistics were conducted with Anova one-way followed by Dunnet's post hoc and significance level of p<0.05. The supplementation induced increase on lipids/proteins oxidation and mitochondrial 3-nitrotyrosine content, an imbalance on enzymatic activity and a decrease on respiratory chain complexes activities. The results suggest that vitamin A induces oxidative/nitrosative stress and mitochondrial impairment on a cardiac level.


Assuntos
Suplementos Nutricionais , Coração/efeitos dos fármacos , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/metabolismo , Miocárdio/citologia , Tirosina/análogos & derivados , Vitamina A/administração & dosagem , Vitamina A/efeitos adversos , Animais , Relação Dose-Resposta a Droga , Transporte de Elétrons/efeitos dos fármacos , Complexo I de Transporte de Elétrons/metabolismo , Complexo II de Transporte de Elétrons/metabolismo , Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Ensaio de Imunoadsorção Enzimática , Masculino , Oxirredução , Estresse Oxidativo , Ratos , Fatores de Tempo , Tirosina/análise , Tirosina/metabolismo
7.
Pharmacol Rep ; 62(1): 185-93, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20360629

RESUMO

While several studies have been conducted on the antioxidant properties of the beta-amino acid taurine, these studies all used concentrations lower than what is found physiologically. This study investigates the scavenging and antioxidant properties of physiological taurine concentrations against different reactive species. No reactivity between taurine and hydrogen peroxide was found; however, taurine exhibited significant scavenging potential against peroxyl radical, nitric oxide, and superoxide donors. This study also evaluated if taurine was able to minimize the in vitro CuZn-superoxide dismutase damage (SOD) induced by peroxynitrite. Taurine prevented both the formation of nitrotyrosine adducts and the decrease in SOD activity caused by peroxynitrite. In addition, taurine prevented the ex vivo damage caused by tert-butyl hydroperoxide in rat liver slices. These experimental data show that taurine, at different physiological concentrations efficiently scavenges many reactive oxygen and nitrogen species. This finding supports the hypothesis that the antioxidant properties of taurine may be critical for the maintenance of cellular functions, and it suggests a more important function of taurine that requires further investigation.


Assuntos
Antioxidantes , Sequestradores de Radicais Livres , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Taurina/farmacologia , Animais , Cromanos/química , Peróxido de Hidrogênio/química , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Nitroprussiato/farmacologia , Oxidantes/química , Ácido Peroxinitroso/antagonistas & inibidores , Ácido Peroxinitroso/toxicidade , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Superóxidos/química , Substâncias Reativas com Ácido Tiobarbitúrico/química , terc-Butil Hidroperóxido/toxicidade
8.
Basic Clin Pharmacol Toxicol ; 107(6): 949-57, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20849525

RESUMO

We examined the antioxidant properties in vitro and the antinociceptive effect of carvacrol (CARV) in several models of pain in mice. CARV presented a strong antioxidant potential according to the TRAP/TAR evaluation; it also presented scavenger activity against nitric oxide and prevented lipid peroxidation in vitro. In mice, when evaluated against acetic acid-induced abdominal writhing, CARV (25, 50 and 100 mg/kg, i.p.) reduced (p < 0.001) the number of writhing compared to the control group, without opioid participation. In the formalin test, CARV also significantly inhibited both the early (neurogenic pain) and the late (inflammatory pain) phases of formalin-induced licking, with inhibition percentage values of 56.8% (100 mg/kg) for the neurogenic phase and 41.2% (25 mg/kg), 73.8% (50 mg/kg) and 99.7% (100 mg/kg) for the inflammatory phase. CARV also produced a significant inhibition of the pain caused by capsaicin (63.1, 67.1 and 95.8%, p < 0.001) and glutamate (46.4, 61.4 and 97.9%, p < 0.01). When assessed in a thermal model of pain, CARV (100 mg/kg, i.p.) caused a significant increase (p < 0.05) in the latency response on the hot-plate test. Such results were unlikely to be provoked by motor abnormality. Together, these results indicate that the properties of CARV should be more thoroughly examined in order to achieve newer tools for management and/or treatment of painful conditions, including those related to pro-oxidant states.


Assuntos
Analgésicos/farmacologia , Antioxidantes/farmacologia , Monoterpenos/farmacologia , Medição da Dor , Dor/prevenção & controle , Animais , Capsaicina/farmacologia , Cimenos , Avaliação de Medicamentos , Formaldeído/efeitos adversos , Masculino , Camundongos , Dor/induzido quimicamente , Extratos Vegetais/farmacologia , Tempo de Reação
9.
Exp Biol Med (Maywood) ; 234(11): 1296-304, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19855071

RESUMO

Many studies have demonstrated that DNA damage may be associated with type 2 diabetes mellitus (T2DM) and its complications. The goal of this study was to evaluate the effects of the potential relationship between fat (thermolyzed) intake, glucose dyshomeostasis and DNA injury in rats. Biochemical parameters related to glucose metabolism (i.e., blood glucose levels, insulin tolerance tests, glucose tolerance tests and fat cell glucose oxidation) and general health parameters (i.e., body weight, retroperitoneal and epididymal adipose tissue) were evaluated in rats after a 12-month treatment with either a high fat or a high thermolyzed fat diet. The high fat diet (HFD) and high fat thermolyzed diet (HFTD) showed increased body weight and impaired insulin sensitivity at the studied time-points in insulin tolerance test (ITT) and glucose tolerance test (GTT). Interestingly, only animals subjected to the HFTD diet showed decreased epididymal fat cell glucose oxidation. We show which high fat diets have the capacity to reduce glycogen synthesis by direct and indirect pathways. HFTD promoted an increase in lipid peroxidation in the liver, demonstrating significant damage in lipids in relation to other groups. Blood and hippocampus DNA damage was significantly higher in animals subjected to HFDs, and the highest damage was observed in animals from the HFTD group. Striatum DNA damage was significantly higher in animals subjected to HFDs, compared with the control group. These results show a positive correlation between high fat diet, glucose dyshomeostasis, oxidative stress and DNA damage.


Assuntos
Dano ao DNA , Gorduras na Dieta/farmacologia , Resistência à Insulina , Temperatura , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , Gorduras na Dieta/administração & dosagem , Glucose/metabolismo , Teste de Tolerância a Glucose , Glicogênio/biossíntese , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Neostriado/efeitos dos fármacos , Neostriado/metabolismo , Oxirredução/efeitos dos fármacos , Carbonilação Proteica/efeitos dos fármacos , Ratos , Ratos Wistar
10.
Rev. bras. farmacogn ; 22(2): 443-450, Mar.-Apr. 2012. graf, tab
Artigo em Inglês | LILACS | ID: lil-624674

RESUMO

Chrysopogon zizanioides (L.) Roberty, Poaceae, is a plant widely used in northeast Brazil in folk medicine for the treatment of various pathological conditions, including inflammatory pain. The present study evaluated the antinociceptive and anti-inflammatory effects of C. zizanioides essential oil (EO) in rodents. EO was further characterized by GC/MS. The major components of EO were identified as khusimol (19.57%), E-isovalencenol (13.24%), α-vetivone (5.25%), β-vetivone (4.87%) and hydroxy-valencene (4.64%). Following intraperitoneal injection (i.p.), EO at 50 and 100 mg/kg significantly reduced the number of writhes (51.9 and 64.9%, respectively) and the number of paw licks during phase 2 (56.7 and 86.2%, respectively) of a formalin model when compared to control group animals. However, EO-treated mice were ineffective at all doses in hot-plate and rota-rod tests. The EO inhibited the carrageenan-induced leukocyte migration to the peritoneal cavity in a dose-dependent manner (34.7, 35.4, and 62.5% at doses of 25, 50 and 100 mg/kg, respectively). In the paw edema test, the EO (100 mg/kg) inhibited all three phases of the edema equally well, suggesting that the EO has a non-selective inhibitory effect on the release or actions of these mediators. Our results suggest possible antinociceptive and anti-inflammatory effects of the EO.

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