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1.
Life Sci ; 207: 246-252, 2018 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-29778806

RESUMO

Olanzapine (OLZ), is used in the treatment of bipolar disorder and schizophrenia, diseases that present oxidative stress in their physiopathology. It has low aqueous solubility, which may lead to low oral bioavailability. The search of new drug delivery systems (DDSs) that may increase dissolution rate of OLZ, associated with the investigation of the antioxidant potential of the loaded-systems become of major importance to understand improvement in bipolar disorder and schizophrenia therapy. Thus, this study aimed to evaluate the in vitro antioxidant potential of two different Layered Double Hydroxides (LDH) loaded with 5% of OLZ (CaAl and NiAl), by radical scavenging activity (2,2-Diphenyl-1-picrylhydrazyl and nitric oxid); radical cation scavenging activity (2,2'-azino-bis3-ethylbenzthiazoline-6-sulfonic acid ABTS) and evaluation of inhibition capacity of lipid peroxidation by thiobarbituric acid (TBARS). The results showed that both obtained LDH systems presented in vitro antioxidant capacity when associated with OLZ in all methods performed, and this activity is more pronounced with the systems containing OLZ compared to pure drug. The systems with CaAl was shown to have increased antioxidant potential, compared to NiAl, increasing the antioxidant activity up to 40,83%, 15,84% and 16,73%, as showed by the DPPH, nitric oxide and TBARS tests, respectively. The results revealed that the use of LDHs as a functional excipient may be promising in the pharmaceutical industry for bipolar disorder and schizophrenia therapy.


Assuntos
Alumínio/química , Antioxidantes/química , Benzodiazepinas/química , Cálcio/química , Hidróxidos/química , Níquel/química , Transtorno Bipolar/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Excipientes/química , Sequestradores de Radicais Livres , Humanos , Peroxidação de Lipídeos , Olanzapina , Estresse Oxidativo/efeitos dos fármacos , Esquizofrenia/tratamento farmacológico , Substâncias Reativas com Ácido Tiobarbitúrico/química
2.
Chem Biol Interact ; 289: 119-128, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29572072

RESUMO

This study aimed to evaluate the anxiolytic-like effect and the possible neuronal mechanism of action of isopentyl ferulate (IF). For this purpose, we used the marble burying test in Swiss albino mice. The biomarkers involved in oxidative stress were measured in the hippocampus homogenate of the test animals. In addition, the toxicity and antioxidant capacities were tested in Artemia salina and rat erythrocytes, respectively. The results suggest that, an acute administration of the IF at doses of 25, 50, 75 and 150 mg/kg (intraperitoneal, i.p.) significantly (p < 0.05) reduced the marble burying behavior of the animals as compared to the vehicle group, which demonstrates a calming effect of this chemical. It was observed that, the pre-treatment with flumazenil (2.5 mg/kg, i.p.), an antagonist of the gamma-amino butyrinc acid (GABAA) receptor, significantly reversed the marble burying behavioral activity in the animals treated with the IF 150 mg/kg dose. Moreover, the reduction in nitrite content and lipid peroxidation levels, while an increased in the reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT) activities were also observed their hippocampus. Although, IF (2.36-14.16 mM) did not show toxicity in A. salina but exhibited a prominent antioxidant capacity in hydrogen peroxide-induced oxidative damage in rat erythrocytes. In conclusion, IF exhibited an anxiety-like effect in mice along with a potent antioxidant capacity, and we suppose it may have neuroprotective effects possibly via GABAergic transmission pathway.


Assuntos
Ansiolíticos/farmacologia , Biomarcadores/metabolismo , Ácidos Cumáricos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Ácido gama-Aminobutírico/metabolismo , Animais , Antioxidantes/metabolismo , Artemia/efeitos dos fármacos , Ácido Ascórbico/farmacologia , Comportamento Animal/efeitos dos fármacos , Catalase/metabolismo , Ácidos Cumáricos/toxicidade , Diazepam/farmacologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Hemólise/efeitos dos fármacos , Hipocampo/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Nitritos/metabolismo , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Testes de Toxicidade
3.
Inflammation ; 40(2): 511-522, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28091830

RESUMO

D-limonene epoxidation generates (+)-limonene epoxide, an understudied compound in the pharmacologically point of view. Herein, we investigated the anti-inflammatory and antinociceptive potentialities of (+)-limonene epoxide and suggested a mechanism of action. The anti-inflammatory potential was analyzed using agents to induce paw edema, permeability, and myeloperoxidase (MPO) activity. Pro-inflammatory cytokines and cell migration of peritoneal cells were also assessed. Antinociceptive effects were evaluated by writhing test induced by acetic acid, formalin, and hot plate assays and contribution of opioid pathways. Pretreated animals with (+)-limonene epoxide showed reduced carrageenan-induced paw edema in all doses (25, 50, and 75 mg/kg) (P < 0.05). At 75 mg/kg, it suppressed edema provoked by compound 48/80, histamine, prostaglandin E2, and serotonin and reduced permeability determined by Evans blue and MPO activity. It also reduced leukocytes, neutrophils, and IL-1ß levels in the peritoneal cavity in comparison with carrageenan group (P < 0.05). (+)-Limonene epoxide diminished abdominal contortions induced by acetic acid (78.9%) and paw licking times in both 1 (41.8%) and 2 (51.5%) phases and a pretreatment with naloxone (3 mg/kg) reverted the antinociceptive action in morphine- and (+)-limonene epoxide-treated groups (P < 0.05). Additionally, it enlarged response times to the thermal stimulus after 60 and 90 min. In conclusion, (+)-limonene epoxide inhibited release/activity of inflammatory mediators, vascular permeability, migration of neutrophils and displayed systemic and peripheral analgesic-dependent effects of the opioid system.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Edema/tratamento farmacológico , Monoterpenos/farmacologia , Animais , Permeabilidade Capilar/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Monoterpenos Cicloexânicos , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Mediadores da Inflamação , Masculino , Camundongos , Monoterpenos/uso terapêutico , Neutrófilos/citologia , Dor/tratamento farmacológico
4.
Oxid Med Cell Longev ; 2015: 212964, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26576218

RESUMO

The aim of this study was to evaluate the oxidative parameters of erythrocytes and genotoxicity in leukocytes of patients with breast cancer. Oxidative parameters were detected by spectrophotometry and genotoxic damage by single cell gel electrophoresis. Twenty-eight women with breast cancer were monitored before chemotherapy and after the second and fourth cycles of therapy with cyclophosphamide and doxorubicin. After the fourth cycle, increases (P < 0.05) in the reactive substances to thiobarbituric acid levels, nitrite content, and superoxide dismutase activity and high rates of DNA damage in leukocytes were observed when compared with healthy women group and baseline levels. Similarly, after the second cycle, the same parameters were increased (P < 0.05) when compared with baseline levels. Increase in catalase activity was detected only after the fourth cycle and reduced glutathione levels and glutathione peroxidase activity were decreased in all cycles when compared with healthy women, as well as after the second and fourth chemotherapy cycles compared to baseline (P < 0.05). Patients with breast cancer presented an indicative of oxidative stress before, during, and after chemotherapy, as well as increased genotoxic damage in all stages of treatment, demonstrating the clinical applicability of this investigation.


Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/sangue , Neoplasias da Mama/tratamento farmacológico , Estresse Oxidativo , Adulto , Antineoplásicos/farmacologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Ensaio Cometa , Ciclofosfamida/farmacologia , Ciclofosfamida/uso terapêutico , Dano ao DNA/efeitos dos fármacos , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Eritrócitos/citologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Feminino , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Humanos , Leucócitos/citologia , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Projetos Piloto , Espectrofotometria , Superóxido Dismutase/metabolismo
5.
An Acad Bras Cienc ; 87(3): 1791-807, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26375017

RESUMO

Casearia sylvestris Swartz is a medicinal plant widely distributed in Brazil. It has anti-inflammatory, antiulcer and antitumor activities and is popularly used to treat snakebites, wounds, diarrhea, flu and chest colds. Its leaves are rich in oxygenated tricyclic cis-clerodane diterpenes, particulary casearins. Herein, we evaluated the antioxidant activities of a fraction with casearins (FC) isolated from C. sylvestris and histological changes on the central nervous system and livers of Mus musculus mice. Firstly, in vitro studies (0.9, 1.8, 3.6, 5.4 and 7.2 µg/mL) revealed EC50 values of 3.7, 6.4 and 0.16 µg/mL for nitrite, hydroxyl radical and TBARS levels, respectively. Secondly, FC (2.5, 5, 10 and 25 mg/kg/day) was intraperitoneally administered to Swiss mice for 7 consecutive days. Nitrite levels in the hippocampus (26.2, 27.3, 30.2 and 26.6 µM) and striatum (26.3, 25.4, 34.3 and 27.5 µM) increased in all treated animals (P < 0.05). Lower doses dropped reduced glutathione, catalase and TBARS levels in the hippocampus and striatum. With the exception of this reduction in TBARS formation, FC displayed only in vitro antioxidant activity. Animals exhibited histological alterations suggestive of neurotoxicity and hepatotoxicity, indicating the need for precaution regarding the consumption of medicinal formulations based on Casearia sylvestris.


Assuntos
Antioxidantes/farmacologia , Encéfalo/efeitos dos fármacos , Casearia/química , Fígado/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Encéfalo/patologia , Fígado/patologia , Masculino , Camundongos
6.
BMJ Open ; 5(4): e006048, 2015 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-25841232

RESUMO

OBJECTIVE: A relation between transfusional IOL (iron overload), HFE status and oxidative damage was evaluated. DESIGN, SETTING AND PARTICIPANTS: An observational cross-sectional study involving 87 healthy individuals and 78 patients with myelodysplastic syndromes (MDS) with and without IOL, seen at University Hospital of the Federal University of Ceará, Brazil, between May 2010 and September 2011. METHODS: IOL was defined using repeated measures of serum ferritin ≥1000 ng/mL. Variations in the HFE gene were investigated using PCR/restriction fragment length polymorphism (RFLP). The biomarkers of oxidative stress (plasmatic malonaldehyde (MDA), glutathione peroxidase (GPx) and superoxide dismutase (SOD)) were determined by spectrophotometry. RESULTS: The HFE gene variations were identified in 24 patients (30.77%) and 5 volunteers (5.74%). The H63D variant was observed in 35% and the C282Y variant as heterozygous in 5% of patients with MDS with IOL. One patient showed double heterozygous variant (C282Y/H63D) and serum ferritin of 11,649 ng/mL. In patients without IOL, the H63D variant was detected in 29.34%. Serum MDA levels were highest in patients with MDS with IOL, with a significant difference when compared with patients without IOL and healthy volunteers, pointing to the relationship between IOL and oxidative stress. The GPx and SOD were also significantly higher in these patients, indicating that lipid peroxidation increase was followed by an increase in antioxidant capacity. Higher ferritin levels were observed in patients with HFE gene variation. 95.7% of patients with MDS with the presence of HFE gene variations had received more of 20 transfusions. CONCLUSIONS: We observed a significant increase in MDA levels in patients with MDS and IOL, suggesting an increased lipid peroxidation in these patients. The accumulation of MDA alters the organisation of membrane phospholipids, contributing to the process of cellular degeneration. Results show that excess iron intensifies the process of cell damage through oxidative stress. TRIAL REGISTRATION NUMBER: Local Ethics Committee (licence 150/2009).


Assuntos
Antígenos de Histocompatibilidade Classe I/genética , Sobrecarga de Ferro/genética , Síndromes Mielodisplásicas/genética , Estresse Oxidativo/genética , Adulto , Idoso , Análise de Variância , Biomarcadores/sangue , Estudos de Casos e Controles , Estudos Transversais , Feminino , Genótipo , Humanos , Sobrecarga de Ferro/etiologia , Masculino , Pessoa de Meia-Idade , Mutação , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/complicações , Polimorfismo de Fragmento de Restrição
7.
Oxid Med Cell Longev ; 2015: 171756, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25653736

RESUMO

BACKGROUNDS: Oxidative stress can result from excessive free-radical production and it is likely implicated as a possible mechanism involved in the initiation and progression of epileptogenesis. Flavonoids can protect the brain from oxidative stress. In the central nervous system (CNS) several flavonoids bind to the benzodiazepine site on the GABAA-receptor resulting in anticonvulsive effects. OBJECTIVE: This review provides an overview about the role of flavonoids in oxidative stress in epilepsy. The mechanism of action of flavonoids and its relation to the chemical structure is also discussed. RESULTS/CONCLUSIONS: There is evidence that suggests that flavonoids have potential for neuroprotection in epilepsy.


Assuntos
Anticonvulsivantes/farmacologia , Epilepsia/patologia , Flavonoides/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Anticonvulsivantes/uso terapêutico , Barreira Hematoencefálica/metabolismo , Sistema Nervoso Central/metabolismo , Epilepsia/tratamento farmacológico , Epilepsia/metabolismo , Flavonoides/metabolismo , Flavonoides/uso terapêutico , Antagonistas de Receptores de GABA-A/farmacologia , Antagonistas de Receptores de GABA-A/uso terapêutico , Humanos , Receptores de GABA-A/química , Receptores de GABA-A/metabolismo
8.
Pharmacol Biochem Behav ; 131: 6-12, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25620677

RESUMO

This study aimed to evaluate a microemulsion system (ME) containing phenobarbital in epilepsy model induced by pilocarpine in rats and to oxidative stress and histologic lesions in hippocampus. The microemulsion was applied to the shaved back of Wistar rats. The animals were divided into the following groups: control group (P400); ME50 40mg/kg, topically-t.p.; ME100, 40mg/kg, t.p.; EM50, 40mg/kg, t.p.; phenobarbital solution 40mg/kg (PS), oral. After 60min, behavioral changes were evaluated for 1h in the model of epileptical crisis induced by pilocarpine. Phenobarbital in microemulsion was able to increase the latency for status epilepticus (SE) (p<0.05), decrease the number of epileptical crisis (ME50: p<0.001; ME100: p<0.01) and decrease mortality rate by 80% compared to P400. In EM50 and PS groups, deaths were decreased by 53.3% and 100% respectively. The ME50 and ME100 groups were able to reduce oxidative stress in experimental animals when compared to the P400. The microemulsion was still capable of reducing neuronal damage in the hippocampal areas. The results of this study come in an innovative way, demonstrating the ability of transdermal ME50 and ME100 to reduce pilocarpine-induced epileptical crisis, oxidative stress, besides neuronal damages.


Assuntos
Anticonvulsivantes/administração & dosagem , Antioxidantes/administração & dosagem , Fenobarbital/administração & dosagem , Pilocarpina/farmacologia , Convulsões/tratamento farmacológico , Administração Cutânea , Animais , Anticonvulsivantes/uso terapêutico , Antioxidantes/uso terapêutico , Modelos Animais de Doenças , Emulsões/administração & dosagem , Feminino , Hipocampo/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fenobarbital/uso terapêutico , Ratos , Ratos Wistar , Convulsões/induzido quimicamente
9.
Chem Biol Interact ; 225: 47-53, 2015 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-25446849

RESUMO

Essential oils have played a prominent role in research on natural products, due to the high level of bioactive constituents, which include those derived from phenylpropanoids or terpenoids. This study aimed to evaluate the antioxidant capacity of isopentyl ferulate (IF) employing in vitro experimental models for elimination of the 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS+), hydroxyl (OH) and nitric oxide (NO), as well as its capacity to electron transfer by reducing potential and inhibition of lipid peroxidation by TBARS (thiobarbituric acid reactive substances) method. In all in vitro antioxidants protocols, isopentyl ferulate showed to be potent in a concentration of 54.4 nM, presenting a percentage inhibition of 91.29±0.57, 92.63±0.28, 83.62±0.18, 77.07±0.72 and 79.51±0.32% for DPPH, ABTS+, hydroxyl, nitric oxide and TBARS level, respectively. The increase of absorbance at 700 nm in the concentrations of 3.4, 6.8, 13.6, 27.2 and 54.4 nM shows the reducing potential of IF. Similar results were obtained with Trolox (559 nM), a hydrophilic synthetic analogue of α-tocopherol, which is widely used as a standard antioxidant. The present study demonstrated that isopentyl ferulate has an antioxidant activity in vitro experimental models, suggesting that this compound could enhance the development of a new product with antioxidant properties. However, further in vivo studies are needed to assign possible implications in the treatment of diseases related with free radicals.


Assuntos
Ácidos Cumáricos/química , Sequestradores de Radicais Livres/química , Benzotiazóis/química , Compostos de Bifenilo/química , Radical Hidroxila/química , Óxido Nítrico/química , Oxirredução , Picratos/química , Ácidos Sulfônicos/química , Substâncias Reativas com Ácido Tiobarbitúrico/análise
10.
Pharmacol Biochem Behav ; 124: 421-4, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24967871

RESUMO

Epilepsy affects about 40 million people worldwide. Many drugs block seizures, but have little effect in preventing or curing this disease. So the search for new drugs for epilepsy treatment using animal models prior to testing in humans is important. Increasingly pharmaceutical industries invest in the Re​search & Drug Development area to seek safe and effective new therapeutic alternatives to the currently available epilepsy treatment. In this perspective, natural compounds have been investigated in epilepsy models, particularly the monoterpenes obtained from medicinal plants. In our study we investigated the effects of cyane-carvone (CC), a synthetic substance prepared from natural a monoterpene, carvone, against pilocarpine- (PILO), pentylenetetrazole- (PTZ) and picrotoxine (PTX)-induced seizures in mice after acute treatment with repeated oral doses (CC 25, 50 and 75 mg/kg) for 14 days. CC in all doses tested showed increase in latency to first seizure, decrease in percentages of seizuring animals as well as reduction percentages of dead animals (p<0.05) in PILO, PTZ and PTX groups when compared with vehicle. However, these effects were not reversed by flumazenil, benzodiazepine (BZD) antagonist used to investigate the CC action mechanism. Our results suggest that acute treatment with CC at the doses tested can exert anticonvulsant effects in PILO, PTZ and PTX epilepsy models. In addition, our data suggest that CC could act in an allosteric site of GABAA, which would be different from the site in which BDZ acts, since flumazenil was not able to reverse any of CC effects on the modulation of seizure parameters related with epilepsy models investigated. New studies should be conducted to investigate CC effects in other neurotransmitter systems. Nevertheless, our study reinforces the hypothesis that CC could be used, after further research, as a new pharmaceutical formulation and a promising alternative for epilepsy treatment, since it showed anticonvulsant effects.


Assuntos
Anticonvulsivantes/uso terapêutico , Modelos Animais de Doenças , Epilepsia/tratamento farmacológico , Monoterpenos/uso terapêutico , Nitrilas/uso terapêutico , Administração Oral , Animais , Anticonvulsivantes/administração & dosagem , Monoterpenos Cicloexânicos , Masculino , Camundongos , Monoterpenos/administração & dosagem , Nitrilas/administração & dosagem
11.
Inflammation ; 37(3): 966-77, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24487978

RESUMO

Cyane-carvone (CC) was studied to elucidate its anti-inflammatory, antinociceptive, and antioxidant effects in Mus musculus. Anti-inflammatory (bradykinin, histamine, prostaglandin E2, serotonin, and carrageenan) and antinociceptive (acetic acid and formalin) models were utilized. Myeloperoxidase activity, interleukin (IL)-1ß, tumor necrosis factor alpha (TNF-α), and glutathione (GSH) levels were evaluated. Analysis of variance followed by Student-Newman-Keuls' test was done. Results were compared with control groups (significantly when p < 0.05). In bradykinin, histamine, prostaglandin E2, and serotonin tests, 75 mg/kg CC decreased significantly paw edema (t = 30, 60, 90, and/or 120 min). In carrageenan test, 50 and 75 mg/kg CC (t = 3 h and t = 4 h) and 25 mg/kg CC (t = 4 h) decreased significantly paw edema. CC (75 mg/kg) inhibited significantly mieloperoxidase activity and decreased IL-1ß and TNF-α, and all doses increased GSH levels. CC (75 mg/kg) decreased significantly the number of contortions of animals and time of licking (phase 2). CC showed anti-inflammatory, antinociceptive, and antioxidant effects in mice.


Assuntos
Analgésicos/farmacologia , Anti-Inflamatórios/farmacologia , Citocinas/biossíntese , Monoterpenos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Bradicinina/antagonistas & inibidores , Carragenina/antagonistas & inibidores , Monoterpenos Cicloexânicos , Dinoprostona/antagonistas & inibidores , Edema/tratamento farmacológico , Glutationa/metabolismo , Antagonistas dos Receptores Histamínicos/farmacologia , Inflamação/tratamento farmacológico , Interleucina-1beta/metabolismo , Masculino , Camundongos , Monoterpenos/química , Dor/tratamento farmacológico , Peroxidase/metabolismo , Antagonistas da Serotonina/farmacologia , Fator de Necrose Tumoral alfa/metabolismo
12.
Brain Res ; 1547: 34-42, 2014 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-24333358

RESUMO

Phytol, a branched chain unsaturated alcohol, is particularly interesting because it is an isolated compound from essential oils of different medicinal plants. The aim of this study was to evaluate the anxiolytic-like effects of phytol in animal models to clarify their possible action mechanism. After acute intraperitoneal treatment with phytol at doses of 25, 50 and 75 mg/kg behavioral models of open-field, elevated-plus-maze, rota-rod, light-dark, marble-burying and pentobarbital sleeping time tests were utilized. In open field test, phytol (25, 50 and 75 mg/kg) [p<0.01] increased the number of crossings and rearings. However, the number of groomings [p<0.01] was reduced. Likewise, the number of entries and the time spent in light space were increased [p<0.01] while the number of marble-burying was decreased [p<0.001], in elevated-plus-maze, light-dark and marble-burying tests, respectively. In motor activity test, phytol (75 mg/kg) impaired the rota-rod performance of mice [p<0.01]. In pentobarbital sleeping time test, phytol 75 mg/kg decreased for latency of sleeping and phytol (25, 50 and 75 mg/kg) increased the sleep time when compared to negative control [p<0.05]. All these effects were reversed by pre-treatment with flumazenil (2.5mg/kg, i.p.), similarly to those observed with diazepam (2mg/kg, i.p.; positive control) suggesting that the phytol presents mechanism of action by interaction with the GABAergic system. These findings suggest that acute administration of phytol exerts an anxiolytic-like effect on mice. Furthermore, suppose that phytol interacts with GABAA receptor, probably at the receptor subtypes that mediate benzodiazepines effects, to produce sedative and anxiolytic activities.


Assuntos
Ansiolíticos/farmacologia , Comportamento Animal/efeitos dos fármacos , Fitol/farmacologia , Sono/efeitos dos fármacos , Animais , Ansiolíticos/administração & dosagem , Flumazenil/farmacologia , Moduladores GABAérgicos/farmacologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Atividade Motora/efeitos dos fármacos , Fitol/administração & dosagem
13.
Pharmacol Biochem Behav ; 116: 64-8, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24201051

RESUMO

Nimodipine has been investigated in the treatment of anxiety. Its administration, however, presents a number of limitations, particularly by low bioavailability, low aqueous solubility and photosensitivity. These difficulties can be resolved by the use of nanometer-scale pharmaceutical carriers. The goal of the present study was thus to develop a liposomal formulation containing nimodipine (NMD-Lipo) and evaluate anxiolytic activity using models of anxiety (open-field, light and dark and elevated plus-maze test). The results suggest that administration of NMD-Lipo has no sedative or muscle relaxant effect in animals, since there was no reduction in the number of crossings, grooming and rearings. The increased residence time of the animals treated with NMD-Lipo in the bright field is a reflection of the anxiolytic-like activity of the formulation. Furthermore, the reduction in residence time of rodents treated with the combination of flumazenil and NMD-Lipo in the illuminated box suggests that NMD-Lipo acts on benzodiazepine receptors. The increase in the number of entries and length of stay in the open arms of mice treated with NMD-Lipo suggests that anxiolytic activity of formulation and reduction in number of entries and length of stay in open arms of rodents treated with a combination of flumazenil and NMD-Lipo suggest that NMD-Lipo act on benzodiazepine receptors.


Assuntos
Ansiolíticos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Lipossomos , Nimodipina/uso terapêutico , Animais , Ansiolíticos/administração & dosagem , Comportamento Animal , Bloqueadores dos Canais de Cálcio/administração & dosagem , Masculino , Camundongos , Nimodipina/administração & dosagem
14.
Neurochem Res ; 38(9): 1861-70, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23765368

RESUMO

The aim of this study was to evaluate the neuroprotective effects of nerolidol in mice hippocampus against oxidative stress in neuronal cells compared to ascorbic acid (positive control) as well as evaluated the nerolidol sedative effects by open field test compared to diazepam (positive control). Thirty minutes prior to behavioral observation on open field test, mice were intraperitoneally treated with vehicle, nerolidol (25, 50 and 75 mg/kg), diazepam (1 mg/kg) or ascorbic acid (250 mg/kg). To clarify the action mechanism of of nerolidol on oxidative stress in animals subjected to the open field test, Western blot analysis of Mn-superoxide dismutase and catalase in mice hippocampus were performed. In nerolidol group, there was a significant decrease in lipid peroxidation and nitrite levels when compared to negative control (vehicle). However, a significant increase was observed in superoxide dismutase and catalase activities in this group when compared to the other groups. Vehicle, diazepam, ascorbic acid and nerolidol groups did not affected Mn-superoxide dismutase, catalase mRNA or protein levels. Our findings strongly support the hypothesis that oxidative stress occurs in hippocampus. Nerolidol showed sedative effects in animals subjected to the open field test. Oxidative process plays a crucial role on neuronal pathological consequence, and implies that antioxidant effects could be achieved using this sesquiterpene.


Assuntos
Antioxidantes/farmacologia , Comportamento Animal/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Sesquiterpenos/farmacologia , Animais , Hipocampo/fisiologia , Camundongos
16.
Fundam Clin Pharmacol ; 27(4): 419-26, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22340189

RESUMO

Farnesol, a sesquiterpene alcohol, has been shown to have antioxidant and anti-inflammatory properties. Recent studies have found that antioxidant compounds may exert a certain protective effect against neurotoxicity. The objective of this study was to evaluate the antinociceptive activity of farnesol (FAR) and its neurotoxic effects on the brains of adult mice. In this study, two mouse models of analgesia were used to evaluate FAR at doses of 50, 100, and 200 mg/kg, injected intraperitoneally (i.p.). In the acetic acid-induced writhing test, a significant decrease was found in the number of contortions in the FAR-treated mice at doses of 50, 100, and 200 mg/kg. FAR was also found to inhibit the licking response in the injected paw at doses of 100 and 200 mg/kg (i.p.) in the first (0-5 min) and second phases (15-30 min) of the formalin test. To evaluate neurotoxic effects, Swiss mice were treated with 0.9% saline (i.p., control group), 0.05 Tween 80 dissolved in 0.9% saline (i.p., vehicle group), and FAR 50, 100, or 200 mg/kg, i.p. Following treatment, all groups were observed for 72 h. In the FAR 200-mg group, 16% of the animals suffered brain injury that affected 12% of the area of the hippocampus. No lesions were found in the hippocampal and striatal regions of the brain in any of the animals treated with the 50 and 100 mg/kg doses of FAR. In conclusion, FAR exerts an antinociceptive effect with no significant neurotoxicity in the brains of adult mice.


Assuntos
Analgésicos/administração & dosagem , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/patologia , Farneseno Álcool/administração & dosagem , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Analgésicos/toxicidade , Animais , Lesões Encefálicas/induzido quimicamente , Lesões Encefálicas/patologia , Farneseno Álcool/toxicidade , Masculino , Camundongos , Medição da Dor/métodos
17.
Neurosci J ; 2013: 949452, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-26317107

RESUMO

The objective of the present study was to evaluate the antinociceptive effects of phytol using chemical and thermal models of nociception in mice and to assess its antioxidant effects in vitro. Phytol was administered intraperitoneally (i.p.) to mice at doses of 25, 50, 100, and 200 mg/kg. In the acetic acid-induced writhing test, phytol significantly reduced the number of contortions compared to the control group (P < 0.001). In the formalin test, phytol reduced significantly the amount of time spent in paw licking in both phases (the neurogenic and inflammatory phases), this effect being more pronounced in the second phase (P < 0.001). Phytol also provoked a significant increase in latency in the hot plate test. These antinociceptive effects did not impaire the motor performance, as shown in the rotarod test. Phytol demonstrated a strong antioxidant effect in vitro in its capacity to remove hydroxyl radicals and nitric oxide as well as to prevent the formation of thiobarbituric acid reactive substances (TBARS). Taken as a whole, these results show the pronounced antinociceptive effects of phytol in the nociception models used, both through its central and peripheral actions, but also its antioxidant properties demonstrated in the in vitro methods used.

18.
Colloids Surf B Biointerfaces ; 103: 642-51, 2013 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-23253474

RESUMO

Clays are materials commonly used in the pharmaceutical industry, either as ingredients or as active ingredients. It was observed that when they are administered concurrently, they may interact with drugs reducing their absorption. Therefore, such interactions can be used to achieve technological and biopharmaceutical advantages, regarding the control of release. This review summarizes bibliographic (articles) and technological (patents) information on the use of systems containing clays and clay minerals in modified drug delivery. In this area, formulations such natural clay, commercial clay, synthetic clay, composites clay-polymers, nanocomposites clay-polymers, films and hidrogels composites clay-polymers are used to slow/extend or vectorize the release of drugs and consequently they increase their bioavailability. Finally, this review summarizes the fields of technology and biopharmaceutical applications, where clays are applied.


Assuntos
Silicatos de Alumínio/química , Sistemas de Liberação de Medicamentos , Minerais/química , Argila , Nanocompostos/química , Patentes como Assunto
19.
Parasitol Res ; 112(2): 603-10, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23086444

RESUMO

Blood flukes of the genus Schistosoma are the causative agents of human schistosomiasis, a debilitating disease that afflicts over 200 million people worldwide. Praziquantel is the drug of choice but concerns over praziquantel resistance have renewed interest in the search for alternative drug therapies. Carvacrol, a naturally occurring monoterpene phenol and food additive, has been shown high medicinal importance, including antimicrobials activities. The aim of this study was to evaluate in vitro effect of carvacryl acetate, a derivative of carvacrol, on Schistosoma mansoni adult worms. We demonstrated that carvacryl acetate at 6.25 µg/mL has antischistosomal activity, affecting parasite motility and viability. Additionally, confocal laser scanning microscopy pictures revealed morphological alterations on the tegumental surface of worms, where some tubercles appeared to be swollen with numerous small blebs emerging from the tegument around the tubercles. Furthermore, experiments performed using carvacryl acetate at sub-lethal concentrations (ranging from 1.562 to 6.25 µg/mL) showed an inhibitory effect on the daily egg output of paired adult worms. Thus, carvacryl acetate is toxic at high doses, while at sub-lethal doses, it significantly interferes with the reproductive fitness of S. mansoni adult worms. Due to its safety and wide use in the industry, carvacryl acetate is a promising natural product-derived compound and it may represent a step forward in the search for novel anthelmintic agents, at a time when there is an urgent need for novel drugs.


Assuntos
Acetatos/farmacologia , Anti-Helmínticos/farmacologia , Monoterpenos/farmacologia , Schistosoma mansoni/efeitos dos fármacos , Animais , Cimenos , Locomoção/efeitos dos fármacos , Microscopia , Reprodução/efeitos dos fármacos , Schistosoma mansoni/anatomia & histologia , Análise de Sobrevida
20.
Cell Mol Neurobiol ; 32(4): 633-40, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22373695

RESUMO

The anticonvulsant effect of cyano-carvone, a monoterpene monocyclic, was investigated in epilepsy model induced by pilocarpine. Cyano-carvone at doses of 25, 50 or 75 mg/kg promoted a reduction of 16.7, 33 and 66.7%, respectively, against pilocarpine-induced seizures, and it was efficacious in increasing both the latency to first seizures and the survival percentage, resulting in 33.3, 67 and 91.7% of protection against death induced by seizures, respectively (P < 0.05). The reference drug atropine (25 mg/kg) also produced a significant protection (100%). Its monoterpene, at 25, 50 and 75 mg/kg, was also capable to increase the latency for installation of status epilepticus induced by pilocarpine, and presented a significant protection against lipid peroxidation and nitrite formation in mice hippocampus (P < 0.05). In addition, it was observed that the cyano-carvone pretreatment increased the acetylcholinesterase activity in mice hippocampus after pilocarpine-induced seizures. The present results clearly indicate the anticonvulsant ability of cyano-carvone, which can be, at least in part, explained by the increased activity of the acetylcholinesterase enzyme. Our data suggest that the action mechanism can also be due to a direct activation of the antioxidant enzymes that could be associated with a reduction observed in oxidative stress in mice hippocampus, probably involving an inhibition of free radical production.


Assuntos
Acetilcolinesterase/metabolismo , Anticonvulsivantes/farmacologia , Monoterpenos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Estado Epiléptico/tratamento farmacológico , Estado Epiléptico/metabolismo , Animais , Anticonvulsivantes/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Modelos Animais de Doenças , Ativação Enzimática/efeitos dos fármacos , Masculino , Camundongos , Monoterpenos/uso terapêutico , Estresse Oxidativo/fisiologia , Estado Epiléptico/enzimologia
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