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1.
Braz J Med Biol Res ; 50(1): e5630, 2017 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-28076453

RESUMO

Previous studies have reported on the glucose and lipid-lowering effects of ferulic acid (FA) but its anti-obesity potential has not yet been firmly established. This study investigated the possible anti-obesitogenic effects of FA in mice fed a high-fat diet (HFD) for 15 weeks. To assess the antiobesity potential of FA, 32 male Swiss mice, weighing 20-25 g (n=6-8 per group) were fed a normal diet (ND) or HFD, treated orally or not with either FA (10 mg/kg) or sibutramine (10 mg/kg) for 15 weeks and at the end of this period, the body weights of animals, visceral fat accumulation, plasma levels of glucose and insulin hormone, amylase and lipase activities, the satiety hormones ghrelin and leptin, and tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCH-1) were analyzed. Results revealed that FA could effectively suppress the HFD-associated increase in visceral fat accumulation, adipocyte size and body weight gain, similar to sibutramine, the positive control. FA also significantly (P<0.05) decreased the HFD-induced elevations in serum lipid profiles, amylase and lipase activities, and the levels of blood glucose and insulin hormone. The markedly elevated leptin and decreased ghrelin levels seen in HFD-fed control mice were significantly (P<0.05) reversed by FA treatment, almost reaching the values seen in ND-fed mice. Furthermore, FA demonstrated significant (P<0.05) inhibition of serum levels of inflammatory mediators TNF-α, and MCH-1. These results suggest that FA could be beneficial in lowering the risk of HFD-induced obesity via modulation of enzymatic, hormonal and inflammatory responses.


Assuntos
Fármacos Antiobesidade/farmacologia , Ácidos Cumáricos/farmacologia , Ciclobutanos/farmacologia , Gordura Intra-Abdominal/efeitos dos fármacos , Obesidade/tratamento farmacológico , Tecido Adiposo/patologia , Animais , Dieta Hiperlipídica , Modelos Animais de Doenças , Masculino , Camundongos , Obesidade/patologia
3.
Psychol Rep ; 116(2): 485-512, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25730748

RESUMO

Children left behind while their parents immigrate or travel for employment are becoming a widespread phenomenon for economic reasons, creating potentially stressful and inadequate developmental support for a substantial portion of some countries' working class populations. This study assessed the emotional status and coping skills of two matched samples of 163 Romanian children left behind and 163 comparable children living with their parents. The State-Trait Anxiety Inventory for Children, the Anger Expression Scale for Children, the Short Mood and Feelings Questionnaire, and the Children's Coping Strategies Checklist were utilized. Higher anxiety and depression were observed in left-behind children compared to the control group living with parents. Hierarchical multiple regression supported the relevance of coping strategies, controlled for sociodemographic characteristics, to help explain anxiety in left-behind children. Strategies to promote psychological health and general well being are discussed.


Assuntos
Adaptação Psicológica/fisiologia , Ansiedade/psicologia , Depressão/psicologia , Núcleo Familiar/psicologia , Migrantes/psicologia , Adolescente , Criança , Emoções Manifestas/fisiologia , Feminino , Humanos , Masculino , Romênia
4.
Mol Psychiatry ; 20(11): 1339-49, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25687775

RESUMO

Human and animal studies have converged to suggest that caffeine consumption prevents memory deficits in aging and Alzheimer's disease through the antagonism of adenosine A2A receptors (A2ARs). To test if A2AR activation in the hippocampus is actually sufficient to impair memory function and to begin elucidating the intracellular pathways operated by A2AR, we have developed a chimeric rhodopsin-A2AR protein (optoA2AR), which retains the extracellular and transmembrane domains of rhodopsin (conferring light responsiveness and eliminating adenosine-binding pockets) fused to the intracellular loop of A2AR to confer specific A2AR signaling. The specificity of the optoA2AR signaling was confirmed by light-induced selective enhancement of cAMP and phospho-mitogen-activated protein kinase (p-MAPK) (but not cGMP) levels in human embryonic kidney 293 (HEK293) cells, which was abolished by a point mutation at the C terminal of A2AR. Supporting its physiological relevance, optoA2AR activation and the A2AR agonist CGS21680 produced similar activation of cAMP and p-MAPK signaling in HEK293 cells, of p-MAPK in the nucleus accumbens and of c-Fos/phosphorylated-CREB (p-CREB) in the hippocampus, and similarly enhanced long-term potentiation in the hippocampus. Remarkably, optoA2AR activation triggered a preferential p-CREB signaling in the hippocampus and impaired spatial memory performance, while optoA2AR activation in the nucleus accumbens triggered MAPK signaling and modulated locomotor activity. This shows that the recruitment of intracellular A2AR signaling in the hippocampus is sufficient to trigger memory dysfunction. Furthermore, the demonstration that the biased A2AR signaling and functions depend on intracellular A2AR loops prompts the possibility of targeting the intracellular A2AR-interacting partners to selectively control different neuropsychiatric behaviors.


Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Hipocampo/metabolismo , Transtornos da Memória/genética , Transtornos da Memória/patologia , Receptores A2 de Adenosina/metabolismo , Transdução de Sinais/genética , Adenosina/análogos & derivados , Adenosina/farmacologia , Agonistas do Receptor A2 de Adenosina/farmacologia , Animais , Membrana Celular/metabolismo , Modelos Animais de Doenças , Comportamento Exploratório/fisiologia , Células HEK293 , Hipocampo/efeitos dos fármacos , Humanos , Técnicas In Vitro , Luz , Transtornos da Memória/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL , Fenetilaminas/farmacologia , Fosforilação/efeitos dos fármacos , Fosforilação/genética , Receptores A2 de Adenosina/genética , Transdução de Sinais/efeitos dos fármacos , Sinaptossomos/metabolismo , Transfecção
5.
Br J Pharmacol ; 172(4): 1074-86, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25296982

RESUMO

BACKGROUND AND PURPOSE: Both cannabinoid CB1 and adenosine A2A receptors (CB1 receptors and A2A receptors) control synaptic transmission at corticostriatal synapses, with great therapeutic importance for neurological and psychiatric disorders. A postsynaptic CB1 -A2A receptor interaction has already been elucidated, but the presynaptic A2A receptor-mediated control of presynaptic neuromodulation by CB1 receptors remains to be defined. Because the corticostriatal terminals provide the major input to the basal ganglia, understanding the interactive nature of converging neuromodulation on them will provide us with novel powerful tools to understand the physiology of corticostriatal synaptic transmission and interpret changes associated with pathological conditions. EXPERIMENTAL APPROACH: Pharmacological manipulation of CB1 and A2A receptors was carried out in brain nerve terminals isolated from rats and mice, using flow synaptometry, immunoprecipitation, radioligand binding, ATP and glutamate release measurement. Whole-cell patch-clamp recordings were made in horizontal corticostriatal slices. KEY RESULTS: Flow synaptometry showed that A2A receptors were extensively co-localized with CB1 receptor-immunopositive corticostriatal terminals and A2A receptors co-immunoprecipitated CB1 receptors in these purified terminals. A2A receptor activation decreased CB1 receptor radioligand binding and decreased the CB1 receptor-mediated inhibition of high-K(+) -evoked glutamate release in corticostriatal terminals. Accordingly, A2A receptor activation prevented CB1 receptor-mediated paired-pulse facilitation and attenuated the CB1 receptor-mediated inhibition of synaptic transmission in glutamatergic synapses of corticostriatal slices. CONCLUSIONS AND IMPLICATIONS: Activation of presynaptic A2A receptors dampened CB1 receptor-mediated inhibition of corticostriatal terminals. This constitutes a thus far unrecognized mechanism to modulate the potent CB1 receptor-mediated presynaptic inhibition, allowing frequency-dependent enhancement of synaptic efficacy at corticostriatal synapses.


Assuntos
Ácido Glutâmico/metabolismo , Receptor A2A de Adenosina/metabolismo , Receptor CB1 de Canabinoide/metabolismo , Receptores Pré-Sinápticos/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/fisiologia , Masculino , Camundongos Knockout , Ratos Wistar , Sinapses/metabolismo , Transmissão Sináptica
6.
Vet Parasitol ; 196(3-4): 341-6, 2013 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-23643453

RESUMO

Anthelmintic resistance has limited the ability to control the gastrointestinal nematodes of small ruminants and has therefore awakened an interest in the study of tanniferous plants as a source of anthelmintics. This study was carried out to evaluate the effect of Mimosa tenuiflora intake, a tanniferous plant that is fed to small ruminants in northeastern Brazil, on the larval establishment of Haemonchus contortus in sheep. In this experiment, 18 nematode-free sheep were divided into three groups (n=6) according to live weight. Group 1 was fed M. tenuiflora leaves; Group 2 was fed M. tenuiflora stems; Group 3 served as the control group and was fed Cynodon dactylon, a plant with low levels of tannins. The animals consumed the plants for 13 days (Day -7 to Day 5). On Day 0, the sheep were experimentally infected with 4500 third-stage H. contortus each. Five days after infection (Day 5), the sheep were slaughtered to count the worm burden and perform a histological analysis of the abomasum. The daily plant intake and the live weight gain of the animals were recorded. The groups that ingested M. tenuiflora leaves and stems consumed less dry matter than did those that ingested C. dactylon (P<0.05). The consumption of M. tenuiflora leaves did not reduce the L3 establishment of H. contortus compared to the control (P>0.05). The intake of M. tenuiflora stems tended toward decreasing larval establishment, but the reduction was not significant (P>0.05). No significant differences were observed in the mucosal cellular response and live weight gain among the groups. These data demonstrated that, with the protocol used, M. tenuiflora has no effect on larval establishment of H. contortus in sheep.


Assuntos
Hemoncose/veterinária , Haemonchus/efeitos dos fármacos , Mimosa/química , Doenças dos Ovinos/parasitologia , Taninos/farmacologia , Ração Animal/análise , Animais , Dieta/veterinária , Feminino , Hemoncose/prevenção & controle , Haemonchus/fisiologia , Larva/efeitos dos fármacos , Componentes Aéreos da Planta/química , Ovinos , Doenças dos Ovinos/tratamento farmacológico , Taninos/química
7.
Br J Pharmacol ; 169(7): 1600-11, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23638679

RESUMO

BACKGROUND AND PURPOSE: Pre-synaptic nicotinic ACh receptors (nAChRs) and adenosine A2A receptors (A2A Rs) are involved in the control of dopamine release and are putative therapeutic targets in Parkinson's disease and addiction. Since A2A Rs have been reported to interact with nAChRs, here we aimed at mapping the possible functional interaction between A2A Rs and nAChRs in rat striatal dopaminergic terminals. EXPERIMENTAL APPROACH: We pharmacologically characterized the release of dopamine and defined the localization of nAChR subunits in rat striatal nerve terminals in vitro and carried out locomotor behavioural sensitization in rats in vivo. KEY RESULTS: In striatal nerve terminals, the selective A2A R agonist CGS21680 inhibited, while the A2A R antagonist ZM241385 potentiated the nicotine-stimulated [(3) H]dopamine ([(3) H]DA) release. Upon blockade of the α6 subunit-containing nAChRs, the remaining nicotine-stimulated [(3) H]DA release was no longer modulated by A2A R ligands. In the locomotor sensitization experiments, nicotine enhanced the locomotor activity on day 7 of repeated nicotine injection, an effect that no longer persisted after 1 week of drug withdrawal. Notably, ZM241385-injected rats developed locomotor sensitization to nicotine already on day 2, which remained persistent upon nicotine withdrawal. CONCLUSIONS AND IMPLICATIONS: These results provide the first evidence for a functional interaction between nicotinic and adenosine A2A R in striatal dopaminergic terminals, with likely therapeutic consequences for smoking, Parkinson's disease and other dopaminergic disorders.


Assuntos
Corpo Estriado/metabolismo , Dopamina/metabolismo , Nicotina/farmacologia , Terminações Pré-Sinápticas/metabolismo , Receptor A2A de Adenosina/metabolismo , Receptores Nicotínicos/metabolismo , Adenosina/análogos & derivados , Adenosina/farmacologia , Agonistas do Receptor A2 de Adenosina/farmacologia , Antagonistas do Receptor A2 de Adenosina/farmacologia , Animais , Regulação da Expressão Gênica , Masculino , Destreza Motora/efeitos dos fármacos , Fenetilaminas/farmacologia , Ratos , Ratos Wistar , Sinaptossomos/efeitos dos fármacos , Sinaptossomos/metabolismo , Triazinas/farmacologia , Triazóis/farmacologia
8.
Braz. j. med. biol. res ; 44(2): 173-181, Feb. 2011. ilus
Artigo em Inglês | LILACS | ID: lil-573654

RESUMO

Statins are among the most prescribed drugs in recent clinical practice. They are also known for their pleiotropic actions, which are independent of their lipid-lowering properties. The effect of lovastatin was investigated against carrageenan-induced paw edema in male Wistar rats (200-250 g) and on leukocyte migration, as measured by carrageenan-induced peritonitis in male Swiss mice (20-25 g), which are models of acute inflammation. Lovastatin (administered 1 h prior to carrageenan), at oral doses of 2, 5, and 10 mg/kg, markedly attenuated paw edema formation in rats at the 4th hour after carrageenan injection (25, 43, and 37 percent inhibition, respectively). Inhibitions of 20, 45 and 80 percent were observed in the leukocyte migration, as evaluated by carrageenan-induced peritonitis in mice with lovastatin doses of 0.5, 1 and 5 mg/kg, as compared to controls. Furthermore, lovastatin (administered 1 h before initiation) reduced the nociceptive effect of the formalin test in mice, at both phases, at doses of 2, 5, and 10 mg/kg: first phase (51, 65, and 70 percent, respectively) and second phase (73, 57, and 66 percent inhibition of licking time, respectively). The anti-nociceptive activity of lovastatin was inhibited by naloxone (3 mg/kg, sc). Lovastatin (0.01, 0.1, and 1 µg/mL) inhibited by 23, 79, and 86 percent, respectively, the release of myeloperoxidase from human neutrophils. Leukocyte (predominantly neutrophils) infiltration was almost completely reduced by lovastatin treatment, as observed in the model of acute paw edema with hematoxylin and eosin staining. In addition, lovastatin decreased the number of cells expressing tumor necrosis factor-α (TNF-α) and the inducible form of nitric oxide synthase (iNOS) activity. Therefore, the alterations in leukocyte activity and cytokine release could contribute to the anti-inflammatory activity of lovastatin.


Assuntos
Animais , Masculino , Camundongos , Ratos , Analgésicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Edema/tratamento farmacológico , Lovastatina/uso terapêutico , Dor/tratamento farmacológico , Carragenina , Edema/induzido quimicamente , Medição da Dor/efeitos dos fármacos , Ratos Wistar
9.
Diabetes Obes Metab ; 13(3): 243-50, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21205116

RESUMO

AIM: D-chiro-inositol (DCI) has been shown to prevent and reverse endothelial dysfunction in diabetic rats and rabbits. The present study evaluates the preventive effect of DCI on experimental diabetic neuropathy (DN). METHODS: Streptozotocin-induced (STZ) diabetic mice were treated by oral gavage for 60 days with DCI (20 mg/kg/12 h) or saline (NaCl 0.9%; 0.1 ml/10 g/12 h; Diab) and compared with euglycaemic groups treated with saline (0.1 ml/10 g/12 h; Eugly). We compared the response of the isolated sciatic nerve, corpora cavernosa or vas deferens to electrical stimulation. RESULTS: The electrically evoked compound action potential of the sciatic nerve was greatly blunted by diabetes. The peak-to-peak amplitude (PPA) was decreased from 3.24 ± 0.7 to 0.9 ± 0.2 mV (p < 0.05), the conduction velocity (CV) of the first component was reduced from 46.78 ± 4.5 to 26.69 ± 3.8 ms (p < 0.05) and chronaxy was increased from 60.43 ± 1.9 to 69.67 ± 1.4 ms (p < 0.05). These parameters were improved in nerves from DCI-treated mice (p < 0.05). PPA in the DCI group was 5.79 ± 0.8 mV (vs. 0.9 ± 0.2 mV-Diab; p < 0.05) and CV was 45.91 ± 3.6 ms (vs. 26.69 ± 3.8 ms-Diab; p < 0.05). Maximal relaxation of the corpus cavernosum evoked by electrical stimulation (2-64 Hz) in the Diab group was 36.4 ± 3.8% compared to 65.4 ± 2.8% in Eugly and 59.3 ± 5.5% in the DCI group (p < 0.05). Maximal contraction obtained in the vas deferens was 38.0 ± 9.2% in Eugly and 11.5 ± 2.6% in Diab (decrease of 69.7%; p < 0.05), compared to 25.2 ± 2.3% in the DCI group (p < 0.05 vs. diabetic). Electron microscopy of the sciatic nerves showed prevention of neuronal damage. CONCLUSIONS: DCI has a neuroprotective action in both autonomic and somatic nerves in STZ-induced DN.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Neuropatias Diabéticas/induzido quimicamente , Inositol/administração & dosagem , Nervo Isquiático/efeitos dos fármacos , Estreptozocina/administração & dosagem , Animais , Diabetes Mellitus Experimental/fisiopatologia , Neuropatias Diabéticas/fisiopatologia , Neuropatias Diabéticas/prevenção & controle , Estimulação Elétrica , Inositol/farmacologia , Masculino , Camundongos , Nervo Isquiático/fisiopatologia , Estreptozocina/farmacologia
10.
Braz J Med Biol Res ; 44(2): 173-81, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21243316

RESUMO

Statins are among the most prescribed drugs in recent clinical practice. They are also known for their pleiotropic actions, which are independent of their lipid-lowering properties. The effect of lovastatin was investigated against carrageenan-induced paw edema in male Wistar rats (200-250 g) and on leukocyte migration, as measured by carrageenan-induced peritonitis in male Swiss mice (20-25 g), which are models of acute inflammation. Lovastatin (administered 1 h prior to carrageenan), at oral doses of 2, 5, and 10 mg/kg, markedly attenuated paw edema formation in rats at the 4th hour after carrageenan injection (25, 43, and 37% inhibition, respectively). Inhibitions of 20, 45 and 80% were observed in the leukocyte migration, as evaluated by carrageenan-induced peritonitis in mice with lovastatin doses of 0.5, 1 and 5 mg/kg, as compared to controls. Furthermore, lovastatin (administered 1 h before initiation) reduced the nociceptive effect of the formalin test in mice, at both phases, at doses of 2, 5, and 10 mg/kg: first phase (51, 65, and 70%, respectively) and second phase (73, 57, and 66% inhibition of licking time, respectively). The anti-nociceptive activity of lovastatin was inhibited by naloxone (3 mg/kg, sc). Lovastatin (0.01, 0.1, and 1 µg/mL) inhibited by 23, 79, and 86%, respectively, the release of myeloperoxidase from human neutrophils. Leukocyte (predominantly neutrophils) infiltration was almost completely reduced by lovastatin treatment, as observed in the model of acute paw edema with hematoxylin and eosin staining. In addition, lovastatin decreased the number of cells expressing tumor necrosis factor-α (TNF-α) and the inducible form of nitric oxide synthase (iNOS) activity. Therefore, the alterations in leukocyte activity and cytokine release could contribute to the anti-inflammatory activity of lovastatin.


Assuntos
Analgésicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Edema/tratamento farmacológico , Lovastatina/uso terapêutico , Dor/tratamento farmacológico , Animais , Carragenina , Edema/induzido quimicamente , Masculino , Camundongos , Medição da Dor/efeitos dos fármacos , Ratos , Ratos Wistar
11.
Neurochem Res ; 35(4): 580-7, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19941068

RESUMO

Reactive oxygen species have been implicated in seizure-induced neurodegeneration, and there is a correlation between free radical level and scavenger enzymatic activity in the epilepsy. It has been suggested that pilocarpine-induced seizures is mediated by an increase in oxidative stress. Current research has found that antioxidant may provide, in a certain degree, neuroprotection against the neurotoxicity of seizures at the cellular level. Alpha-tocopherol has numerous nonenzymatic actions and is a powerful liposoluble antioxidant. The objective of the present study was to evaluate the neuroprotective effects of alpha-tocopherol (TP) in rats, against oxidative stress caused by pilocarpine-induced seizures. 30 min prior to behavioral observation, Wistar rats were treated with, 0.9% saline (i.p., control group), TP (200 mg/kg, i.p., TP group), pilocarpine (400 mg/kg, i.p., P400 group), or the combination of TP (200 mg/kg, i.p.) and pilocarpine (400 mg/kg, i.p.). After the treatments all groups were observed for 6 h. The enzymatic activities, lipid peroxidation and nitrite concentrations were measured using speccitrophotometric methods and these data were assayed. In P400 group mice there was a significant increase in lipid peroxidation and nitrite levels. However, no alteration was observed in superoxide dismutase (SOD) and catalase activities. In the TP and pilocarpine co-administered mice, antioxidant treatment significantly reduced the lipid peroxidation level and nitrite content, as well as increased the SOD and catalase activities in rat hippocampus after seizures. Our findings strongly support the hypothesis that oxidative stress occurs in hippocampus during pilocarpine-induced seizures, indicate that brain damage induced by the oxidative process plays a crucial role in seizures pathogenic consequences, and imply that strong protective effect could be achieved using alpha-tocopherol.


Assuntos
Hipocampo/efeitos dos fármacos , Estresse Oxidativo , Pilocarpina/toxicidade , Convulsões/induzido quimicamente , alfa-Tocoferol/farmacologia , Animais , Catalase/metabolismo , Hipocampo/enzimologia , Hipocampo/metabolismo , Peroxidação de Lipídeos , Masculino , Ratos , Ratos Wistar , Convulsões/metabolismo , Superóxido Dismutase/metabolismo
12.
J Antimicrob Chemother ; 59(5): 934-40, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17376793

RESUMO

OBJECTIVES: The aims of this study were to test the essential oil from Lippia sidoides Cham. for antifungal activity, in vitro, against Candida spp. and Microsporum canis, to evaluate its acute and subchronic toxicological effects, in vivo, and to determine its chemical constituents. METHODS: The antifungal activity, in vitro, was initially evaluated by the agar-well diffusion technique, and the MIC and minimum fungicidal concentration (MFC) were determined by the broth microdilution method. The acute and subchronic toxicological effects were determined in mice and rats, respectively. The chemical composition of the essential oil was determined by gas chromatography coupled to mass spectroscopy. RESULTS: The essential oil obtained from L. sidoides was effective against all tested strains by the agar-well diffusion method. The MICs of L. sidoides essential oil for strains of M. canis ranged from 4 to 70 mg/L and the MFCs ranged from 9 to 150 mg/L. The MICs for strains of Candida spp. ranged from 620 to 2500 mg/L and the MFCs ranged from 1250 to 5000 mg/L. The main constituents of L. sidoides essential oil were thymol (59.65%), E-caryophyllene (10.60%) and p-cymene (9.08%). The acute administration of the essential oil up to 3 g/kg by the oral route to mice was devoid of overt toxicity. The 30 day oral administration of L. sidoides oil (117.95 mg/kg/day) to rats did not induce any significant histopathological, haematological or serum biochemical alterations. CONCLUSIONS: The essential oil from L. sidoides may be a promising source in the search for new antifungal drugs due to its efficacy and low toxicity.


Assuntos
Candida/efeitos dos fármacos , Lippia/química , Microsporum/efeitos dos fármacos , Óleos Voláteis/farmacologia , Óleos Voláteis/toxicidade , Animais , Antifúngicos/administração & dosagem , Antifúngicos/farmacologia , Antifúngicos/toxicidade , Camundongos , Óleos Voláteis/administração & dosagem , Ratos , Ratos Wistar
13.
Biochim Biophys Acta ; 1691(2-3): 79-90, 2004 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-15110989

RESUMO

Li(+) transport, intracellular immobilisation and Li(+)/Mg(2+) competition were studied in Li(+)-loaded bovine chromaffin cells. Li(+) influx rate constants, k(i), obtained by atomic absorption (AA) spectrophotometry, in control (without and with ouabain) and depolarising (without and with nitrendipine) conditions, showed that L-type voltage-sensitive Ca(2+) channels have an important role in Li(+) uptake under depolarising conditions. The Li(+) influx apparent rate constant, k(iapp), determined under control conditions by (7)Li NMR spectroscopy with the cells immobilised and perfused, was much lower than the AA-determined value for the cells in suspension. Loading of cell suspensions with 15 mmol l(-1) LiCl led, within 90 min, to a AA-measured total intracellular Li(+) concentration, [Li(+)](iT)=11.39+/-0.56 mmol (l cells)(-1), very close to the steady state value. The intracellular Li(+) T(1)/T(2) ratio of (7)Li NMR relaxation times of the Li(+)-loaded cells reflected a high degree of Li(+) immobilisation in bovine chromaffin cells, similar to neuroblastoma, but larger than for lymphoblastoma and erythrocyte cells. A 52% increase in the intracellular free Mg(2+) concentration, Delta[Mg(2+)](f)=0.27+/-0.05 mmol (l cells)(-1) was measured for chromaffin cells loaded with the Mg(2+)-specific fluorescent probe furaptra, after 90-min loading with 15 mmol l(-1) LiCl, using fluorescence spectroscopy, indicating significant displacement of Mg(2+) by Li(+) from its intracellular binding sites. Comparison with other cell types showed that the extent of intracellular Li(+)/Mg(2+) competition at the same Li(+) loading level depends on intracellular Li(+) transport and immobilisation in a cell-specific manner, being maximal for neuroblastoma cells.


Assuntos
Células Cromafins/metabolismo , Lítio/metabolismo , Magnésio/metabolismo , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio Tipo L/metabolismo , Bovinos , Células Cultivadas , Células Cromafins/citologia , Células Cromafins/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Nitrendipino/farmacologia , Espectrofotometria Atômica
14.
Vascul Pharmacol ; 39(6): 303-7, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14567068

RESUMO

Kaurenoic acid, a diterpene from Copaifera langsdorffii (Leguminaceae), was evaluated on rat colitis induced by acetic acid. Rats were pretreated orally (15 and 2 h before) or rectally 2 h before induction of colitis with kaurenoic acid (50 and 100 mg/kg) or vehicle (1 ml, 3% DMSO). Colitis was induced by intracolonic instillation of a 2 ml of 4% (v/v) acetic acid solution and, 24 h later, the colonic mucosal damage was analysed macroscopically for the severity of mucosal damage, the myeloperoxidase (MPO) activity and the malondialdehyde (MDA) levels in the colon segments. A marked reduction in gross damage score (52% and 42%) and wet weight of damaged colon tissue (39% and 32%) were observed in rats that received 100 mg/kg kaurenoic acid, respectively, by rectal and oral routes. This effect was confirmed biochemically by a two- to three-fold reduction of colitis associated increase in MPO activity, the marker of neutrophilic infiltration and by a marked decrease in MDA level, an indicator of lipoperoxidation in colon tissue. Furthermore, light microscopy revealed the marked diminution of inflammatory cell infiltration and submucosal edema formation in the colon segments of rats treated with the test compound. These findings indicate the anti-inflammatory potential of kaurenoic acid in acetic acid-induced colitis.


Assuntos
Anti-Inflamatórios não Esteroides , Colite/tratamento farmacológico , Diterpenos/uso terapêutico , Fabaceae/química , Ácido Acético , Administração Oral , Administração Retal , Animais , Brasil , Colite/induzido quimicamente , Colite/patologia , Diterpenos/administração & dosagem , Mucosa Intestinal/patologia , Masculino , Malondialdeído/metabolismo , NF-kappa B/antagonistas & inibidores , Peroxidase/metabolismo , Ratos , Ratos Wistar
15.
J Pharm Pharmacol ; 53(4): 505-11, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11341367

RESUMO

The effects of 1,8-cineole on D-galactosamine/lipopolysaccharide (GalN/LPS)-induced shock model of liver injury was investigated in mice. The co-administration of GalN (700 mg kg(-1), i.p.) and LPS (5 microg kg(-1), i.p.) greatly elevated serum concentrations of tumour necrosis factor-alpha (TNF-alpha), alanine aminotransferase and aspartate aminotransferase, and induced massive hepatic necrosis and lethality in 100% of control mice. Pretreatment with 1,8-cineole (400 mg kg(-1), p.o.) and dexamethasone (1 mg kg(-1), s.c.), 60 min before GalN/LPS, offered complete protection (100%) against the lethal shock and acute elevation in serum TNF-alpha and serum transaminases. Hepatic necrosis induced by GalN/LPS was also greatly reduced by both 1,8-cineole and dexamethasone treatment. The results indicate that 1,8-cineole protects mice against GalN/LPS-induced liver injury through the inhibition of TNF-alpha production, and suggest that 1,8-cineole may be a promising agent to combat septic-shock-associated pathologies.


Assuntos
Cicloexanóis , Falência Hepática/prevenção & controle , Mentol/análogos & derivados , Mentol/farmacologia , Monoterpenos , Choque Séptico/fisiopatologia , Solventes/farmacologia , Terpenos , Animais , Modelos Animais de Doenças , Eucaliptol , Galactosamina/administração & dosagem , Galactosamina/efeitos adversos , Lipopolissacarídeos/administração & dosagem , Lipopolissacarídeos/efeitos adversos , Falência Hepática/etiologia , Masculino , Camundongos , Choque Séptico/complicações , Transaminases/biossíntese , Transaminases/metabolismo , Fator de Necrose Tumoral alfa/biossíntese
16.
Brain Res ; 903(1-2): 62-5, 2001 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-11382388

RESUMO

Nicotine-induced catecholamine (CA) secretion and inward ionic currents were inhibited by the opioid antagonist naloxone in cultured bovine chromaffin cells. Naloxone inhibited nicotine-induced CA secretion, as detected by an on-line real-time electrochemical technique, in a dose-dependent manner (IC(50)=29 microM). In voltage-clamped chromaffin cells, nicotine (10 microM) evoked an average peak inward current of -146 pA that was inhibited by low concentrations of naloxone (42% at 0.1 microM). The antagonist also inhibited total charge influx associated with nicotinic receptor activation (53% at 0.1 microM). This provides strong evidence that naloxone modulation of nicotine-induced CA secretion does not involve opioid receptors but results from the direct interaction with the nicotinic receptor itself, which might also be the case for other related opioid compounds.


Assuntos
Catecolaminas/metabolismo , Células Cromafins/fisiologia , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Nicotina/farmacologia , Agonistas Nicotínicos/farmacologia , Animais , Bovinos , Células Cromafins/citologia , Células Cromafins/metabolismo , Relação Dose-Resposta a Droga , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Peptídeos Opioides/antagonistas & inibidores , Técnicas de Patch-Clamp , Receptores Nicotínicos/fisiologia
17.
Int J Biochem Cell Biol ; 32(5): 557-69, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10736571

RESUMO

Using clonal insulin-secreting BRIN-BD11 cells, we have assessed whether the graded response of the whole cell population to glucose can be accounted for by a dose-dependent recruitment of individual cells, an amplification of the response of the recruited cells or both. Cytosolic free Ca(2+) concentration ([Ca(2+)](i)) is an established index of beta-cell function. We used fura-2 microfluorescence techniques to assess the [Ca(2+)](i) responsiveness of single BRIN-BD11 cells to glucose and other secretagogues. Glucose (1-16.7 mM) evoked oscillatory [Ca(2+)](i) rises in these cells resembling those found in parental rat pancreatic beta-cells. The percentage of glucose-responsive cells was 11% at 1 mM and increased to 40-70% at 3-16.7 mM glucose, as assessed by a single-stimulation protocol. This profile was unrelated to possible differences in the cell cycle, as inferred from experiments where the cultured cells were synchronized by a double thymidine block protocol. Individual cells exhibited variable sensitivities to glucose (threshold range: 1-5 mM) and a variable dose-dependent amplification of the [Ca(2+)](i) responses (EC(50) range: 2-10 mM), as assessed by a multiple-stimulation protocol. Glyceraldehyde and alpha-ketoisocaproic acid had glucose-like effects on [Ca(2+)](i). The data support a mixed model for the activation of insulin-secreting cells. Specifically, the graded secretory response of the whole cell population is likely to reflect both a recruitment of individual cells with different sensitivities to glucose and a dose-dependent amplification of the response of the recruited cells.


Assuntos
Sinalização do Cálcio , Glucose/metabolismo , Insulina/metabolismo , Ilhotas Pancreáticas/citologia , Ilhotas Pancreáticas/metabolismo , Animais , Sinalização do Cálcio/efeitos dos fármacos , Células Clonais , Relação Dose-Resposta a Droga , Fura-2/química , Glucose/farmacologia , Secreção de Insulina , Cetoácidos/metabolismo , Cetoácidos/farmacologia , Manoeptulose/metabolismo , Manoeptulose/farmacologia , Ratos
18.
J Pharm Pharmacol ; 51(2): 125-9, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10217309

RESUMO

Aflatoxin B1, a metabolite of Aspergillus flavus is a potent hepatotoxic and hepatocarcinogenic mycotoxin. Lipid peroxidation and oxidative DNA damage are the principal manifestations of aflatoxin B1-induced toxicity which could be mitigated by antioxidants. Many plant constituents, e.g. flavonoids, lignans and spice principles (capsaicin, curcumin, eugenol, etc.) have been reported to prevent liver damage associated with lipid peroxidation. In this study we investigated ternatin, a tetramethoxyflavone isolated from Egletes viscosa, for possible protection against liver injury induced by aflatoxin B1 in rats. Seventy two hours after a single intraperitoneal dose of aflatoxin B1 (1 mg kg(-1)), the concentration of malondialdehyde, the product of lipid peroxidation in liver homogenates, and serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly elevated (P<0.001). Subcutaneous ternatin (25 mg kg(-1)) pretreatment greatly reduced aflatoxin B1-induced increases in the levels of serum enzymes (ALT from 5071+/-763 to 293+/-66 international units L(-1) and AST from 4241+/-471 to 449+/-108 international units L(-1)) and elevated malondialdehyde levels (from 11.37+/-1.27 to 0.79+/-0.22 nmol (mg wet tissue)(-1)) in a manner similar to oral vitamin E (300 mg kg(-1)), a standard antioxidant. Further, histological changes induced by aflatoxin B1 such as hepatocellular necrosis and bile-duct proliferation were markedly inhibited in animals pretreated with ternatin or vitamin E. These data provide evidence that ternatin inhibits lipid peroxidation and affords protection against liver damage induced by aflatoxin B1. Ternatin might, therefore, be a suitable candidate for the chemoprevention of aflatoxicosis associated liver cancer.


Assuntos
Aflatoxina B1/efeitos adversos , Anti-Inflamatórios não Esteroides/farmacologia , Carcinógenos/efeitos adversos , Flavonoides/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Alanina Transaminase/sangue , Alanina Transaminase/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Aspartato Aminotransferases/sangue , Aspartato Aminotransferases/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas , Flavonoides/uso terapêutico , Fígado/metabolismo , Fígado/patologia , Hepatopatias/tratamento farmacológico , Hepatopatias/patologia , Masculino , Malondialdeído/metabolismo , Plantas Medicinais/química , Ratos , Ratos Wistar , Vitamina E/farmacologia , Vitamina E/uso terapêutico
19.
Gen Pharmacol ; 33(6): 479-85, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10647773

RESUMO

Intraperitoneal injection of pilocarpine (0.75-3.0 mg/kg) caused a dose-related seminal emission in adult male rats. The seminal emission response to 3 mg/kg of pilocarpine was greatly reduced in atropinized (5 and 10 mg/kg, SC) animals, suggesting a cholinomimetic effect. Nw-nitro-L-arginine methyl ester (5, 10, and 20 mg/kg, SC), a nitric oxide synthesis inhibitor, also inhibited the pilocarpine-induced seminal emission, which was reversed by L-arginine (600 mg/kg, SC) or by coinjection of sodium nitroprusside (0.5 mg/kg, SC). Urine analysis for levels of nitric oxide metabolites, nitrate/nitrite (NO3-/NO2-), showed marked alterations in accordance with the drug treatments. The results suggest that nitric oxide mediates the inhibitory neurotransmission responsible for seminal emission in pilocarpine stimulated rats.


Assuntos
Agonistas Muscarínicos/farmacologia , Óxido Nítrico/fisiologia , Pilocarpina/farmacologia , Sêmen/efeitos dos fármacos , Animais , Arginina/farmacologia , Atropina/farmacologia , Masculino , NG-Nitroarginina Metil Éster/farmacologia , Nitratos/urina , Nitritos/urina , Nitroprussiato/farmacologia , Área Pré-Óptica/fisiologia , Ratos , Ratos Wistar
20.
J Physiol ; 510 ( Pt 1): 135-43, 1998 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-9625872

RESUMO

1. Glucose-induced insulin release from single islets of Langerhans is pulsatile. We have investigated the correlation between changes in cytosolic free calcium concentration ([Ca2+]i) and oscillatory insulin secretion from single mouse islets, in particular examining the basis for differences in secretory responses to intermediate and high glucose concentrations. Insulin release was monitored in real time through the amperometric detection of the surrogate insulin marker 5-hydroxytryptamine (5-HT) via carbon fibre microelectrodes. The [Ca2+]i was simultaneously recorded by whole-islet fura-2 microfluorometry. 2. In 82 % of the experiments, exposure to 11 mM glucose evoked regular high-frequency (average, 3.4 min-1) synchronous oscillations in amperometric current and [Ca2+]i. In the remaining experiments (18 %), 11 mM glucose induced an oscillatory pattern consisting of high-frequency [Ca2+]i oscillations that were superimposed on low-frequency (average, 0.32 min-1) [Ca2+]i waves. Intermittent high-frequency [Ca2+]i oscillations gave rise to a similar pattern of pulsatile 5-HT release. 3. Raising the glucose concentration from 11 to 20 mM increased the duration of the steady-state [Ca2+]i oscillations without increasing their amplitude. In contrast, both the duration and amplitude of the associated 5-HT transients were increased by glucose stimulation. The amount of 5-HT released per secretion cycle was linearly related to the duration of the underlying [Ca2+]i oscillations in both 11 and 20 mM glucose. The slopes of the straight lines were identical, indicating that there is no significant difference between the ability of calcium oscillations to elicit 5-HT/insulin release in 11 and 20 mM glucose. 4. In situ 5-HT microamperometry has the potential to resolve the high-frequency oscillatory component of the second phase of glucose-induced insulin secretion. This component appears to reflect primarily the duration of the underlying [Ca2+]i oscillations, suggesting that glucose metabolism and/or access to glucose metabolites is not rate limiting to fast pulsatile insulin release.


Assuntos
Cálcio/metabolismo , Insulina/metabolismo , Membranas Intracelulares/metabolismo , Ilhotas Pancreáticas/metabolismo , Serotonina/metabolismo , Animais , Citosol/metabolismo , Condutividade Elétrica , Glucose/farmacologia , Técnicas In Vitro , Secreção de Insulina , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/fisiologia , Camundongos , Oscilometria , Concentração Osmolar , Fluxo Pulsátil/fisiologia
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