RESUMO
We present our results on the synthesis and preliminary in silico and in vitro studies of the toxicology and antioxidant properties of selenylated analogs of Tacrine. Initially, we synthesized 2-aminobenzonitriles containing an organic selenium moiety, resulting in sixteen compounds with various substituents linked to the portion derived from diorganyl diselenide. These compounds were then used as substrates in reactions with cyclic ketones, in the presence of 1.4 equivalents of trifluoroboroetherate as a Lewis acid, to synthesize selenylated analogs of Tacrine with yields ranging from 20% to 87%. In silico studies explored computational parameters related to antioxidant activity and hepatotoxicity. In vitro studies elucidated the antioxidant effects of Tacrine and its selenium hybrid (TSe) in neutralizing ABTS radicals, scavenging DPPH radicals, and reducing iron ions. Additionally, the acute oral toxicity of one synthesized compound was evaluated.
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New compounds and pharmacological strategies offer alternatives for treating chronic skin diseases, such as atopic dermatitis (AD). Here, we investigated the incorporation of 1,4-anhydro-4-seleno-d-talitol (SeTal), a bioactive seleno-organic compound, in gelatin and alginate (Gel-Alg) polymeric films as a strategy for improving the treatment and attenuation of AD-like symptoms in a mice model. Hydrocortisone (HC) or vitamin C (VitC) were incorporated with SeTal in the Gel-Alg films, and their synergy was investigated. All the prepared film samples were able to retain and release SeTal in a controlled manner. In addition, appreciable film handling facilitates SeTal administration. A series of in-vivo/ex-vivo experiments were performed using mice sensitized with dinitrochlorobenzene (DNCB), which induces AD-like symptoms. Long-term topical application of the loaded Gel-Alg films attenuated disease symptoms and pruritus, with suppression of the levels of inflammatory markers, oxidative damage, and the skin lesions associated with AD. Moreover, the loaded films showed superior efficiency in attenuating the analyzed symptoms when compared to hydrocortisone (HC) cream, a traditional AD-treatment, and decreased the inherent drawbacks of this compound. In short, incorporating SeTal (by itself or with HC or VitC) in biopolymeric films provides a promising alternative for the long-term treatment of AD-type skin diseases.
Assuntos
Dermatite Atópica , Camundongos , Animais , Dermatite Atópica/tratamento farmacológico , Alginatos , Hidrocortisona , Gelatina , Pele/metabolismo , Camundongos Endogâmicos BALB C , Citocinas/metabolismoRESUMO
RATIONALE: Depression is often associated with memory impairment, a clinical feature of Alzheimer's disease (AD), but no effective treatment is available. 7-Chloro-4-(phenylselanyl) quinoline (4-PSQ) has been studied in experimental models of diseases that affect the central nervous system. OBJECTIVES: The pharmacological activity of 4-PSQ in depressive-like behavior associated with memory impairment induced by acute restraint stress (ARS) in male Swiss mice was evaluated. METHODS: ARS is an unavoidable stress model that was applied for a period of 240 min. Ten minutes after ARS, animals were intragastrically treated with canola oil (10 ml/kg) or 4-PSQ (10 mg/kg) or positive controls (paroxetine or donepezil) (10 mg/kg). Then, after 30 min, mice were submitted to behavioral tests. Corticosterone levels were evaluated in plasma and oxidative stress parameters; monoamine oxidase (MAO)-A and MAO -B isoform activity; mRNA expression levels of kappa nuclear factor B (NF-κB); interleukin (IL)-1ß, IL-18, and IL-33; phosphatidylinositol-se-kinase (PI3K); protein kinase B (AKT2), as well as acetylcholinesterase activity were evaluated in the prefrontal cortex and hippocampus. RESULTS: 4-PSQ attenuated the depressive-like behavior, self-care, and memory impairment caused by ARS. Based on the evidence, we believe that effects of 4-PSQ may be associated, at least in part, with the attenuation of HPA axis activation, attenuation of alterations in the monoaminergic system, modulation of oxidative stress, reestablishment of AChE activity, modulation of the PI3K/AKT2 pathway, and reduction of neuroinflammation. CONCLUSIONS: These results suggested that 4-PSQ exhibited an antidepressant-like effect and attenuated the memory impairment induced by ARS, and it is a promising molecule to treat these comorbidities.
Assuntos
Quinolinas , Selênio , Acetilcolinesterase/metabolismo , Animais , Depressão/tratamento farmacológico , Hipocampo/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Camundongos , Doenças Neuroinflamatórias , Estresse Oxidativo , Sistema Hipófise-Suprarrenal/metabolismo , Quinolinas/farmacologiaRESUMO
BACKGROUND: Atopic dermatitis (AD) is a multifactorial chronic inflammatory disease that affects â¼20 % of children and 3% of adults globally and is generally treated by the topical application of steroidal drugs that have undesirable side-effects. The development of alternative therapies is therefore an important objective. The present study investigated the effects of topical treatment with a novel water-soluble selenium-containing carbohydrate derivative (4-anhydro-4-seleno-D-tatitol, SeTal) on the symptoms and inflammatory parameters in an AD mouse model. METHODS: Mice were sensitized by applying 2,4-dinitrochlorobenzene (DNCB) to their dorsal skin on days 1-3, then further challenged on their ears and dorsal skin on days 14, 17, 20, 23, 26, and 29. SeTal (1 and 2%) or hydrocortisone (1%) was applied topically to the backs of the mice from days 14-29, and skin severity scores and scratching behavior determined on day 30. The mice were euthanized, and their ears and dorsal skin removed to quantify inflammatory parameters, edema, myeloperoxidase (MPO) activity, and AD-associated cytokines (tumor necrosis factor alpha (TNF-α), interleukins (IL)-18, and IL-33). RESULTS: DNCB treatment induced skin lesions and increased the scratching behavior, ear edema, MPO activity (ear and dorsal skin), and cytokine levels in dorsal skin. Topical application of SeTal improved inflammatory markers (cytokine levels and MPO activity), cutaneous severity scores, and scratching behavior. CONCLUSION: The efficacy of SeTal was satisfactory in the analyzed parameters, showing similar or better results than hydrocortisone. SeTal appears to be therapeutically advantageous for the treatment and control of AD.
Assuntos
Dermatite Atópica , Animais , Citocinas , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/tratamento farmacológico , Dinitroclorobenzeno , Modelos Animais de Doenças , Hexoses , Hidrocortisona , Mediadores da Inflamação , Camundongos , Camundongos Endogâmicos BALB C , Compostos Organosselênicos , PeleRESUMO
RATIONALE: Obesity is considered one of the major global health problems and increases the risk of several medical complications, such as diabetes and mental illnesses. OBJECTIVE: The present study investigated the effect of 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) on obesity parameters, behavioral and neurochemical alterations in hypothalamic obese rats. METHODS: Male Wistar rats received subcutaneous neonatal injections of monosodium glutamate (MSG, 4g/kg) or saline. After the Lee Index evaluation, rats were divided into groups and treated with 4-PSQ (5 mg/kg, intragastric route) or canola oil once a day (post-natal days (PND) 60â76). Open-field, elevated plus-maze, forced swim task, object recognition/location memory, and stepdown inhibitory avoidance tasks were conducted from PND 66 to 74. On PND 76, rats were euthanized and epididymal fat, blood, cerebral cortex, andhippocampus were removed. Blood biochemical parameters and cortical/hippocampal acetylcholinesterase (AChE) and Na /K -ATPase activities were assessed. RESULTS: MSG increased the Lee Index characterizing the chemically induced hypothalamic obesity model. 4-PSQ reversed the increases of epididymal fat, blood glucose, and triglyceride levels caused by MSG exposure. 4-PSQ attenuated anxiety-like and depression-like behaviors induced by neonatal administrations of MSG. Memory deficits found in MSG-obese rats were reversed by treatment with 4-PSQ. Neurochemical alterations produced by MSG evidenced by stimulation ofNa+/K+-ATPase and AChE activities in the cerebral cortex and hippocampus of rats were normalized by 4-PSQ treatment. CONCLUSIONS: In brief, 4-PSQ therapy improved hypothalamic obesity-related parameters, as well as psychiatric symptoms, cognitive impairment, and neurochemical alterations found in obese rats.
Assuntos
Hipotálamo/efeitos dos fármacos , Obesidade/tratamento farmacológico , Obesidade/psicologia , Quinolinas/administração & dosagem , Selênio/administração & dosagem , Animais , Hipotálamo/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Obesidade/induzido quimicamente , Obesidade/metabolismo , Ratos , Ratos Wistar , Glutamato de Sódio/toxicidadeRESUMO
Atopic dermatitis (AD) is the most common chronic inflammatory skin disease with nasty effects on the psychosocial wellbeing of patients. Overall, glucocorticoids, such as hydrocortisone (HC), are the primary pharmacologic drugs used to treat AD and its symptoms. However, the long-term treatment with HC is often accompanied by severe adverse effects. So, this study reports the encapsulation of HC in polymeric films based on gelatin (Gel) and gelatin/starch (Gel/St) and investigates their potential to treat and attenuate 2,4-Dinitrochlorobenzene (DNCB)-induced AD-like symptoms in BALB/c mice model. The prepared films were characterized by different techniques, which indicated that HC was physically entrapped into the polymer matrices. In vitro experiments indicate that the HC release process occurs in a controlled manner (up to 48 h) for both films. Regarding the in vivo experiments, HC-loaded films (Gel@HC and Gel/St@HC), unloaded films (Gel and Gel/St) and HC cream (1%) (as reference) were applied topically on the back of the DNCB-sensitized animals and skin severity scores and scratching behavior were determined. Ex-vivo experiments were done to quantify inflammatory and/or biochemical parameters. As assessed, the topical application of the biopolymeric films (loaded or not with HC) improved the inflammatory parameters, while a lower corticosterone level was observed for the animals treated with Gel and Gel@HC films. In summary, the HC-loaded films showed superior efficiency to treat/attenuate the analyzed parameter than the HC cream (1%). Further, no death or sign of toxicity was observed in animals exposed to HC-loaded films. Thus, the encapsulation of HC in biopolymeric films seems to be a promising alternative for the treatment of injuries caused by chronic skin diseases that require prolonged use of glucocorticoids.
Assuntos
Hidrocortisona , Dermatopatias , Animais , Preparações de Ação Retardada , Dinitroclorobenzeno , Humanos , Camundongos , Camundongos Endogâmicos BALB C , PeleRESUMO
Recently, we demonstrated the promising anxiolytic action of 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) in mice. For this reason, the objective of this study was to expand our previous findings by investigating the contribution of serotoninergic and GABAergic systems to the anxiolytic action of this compound. Pretreatment with different serotoninergic antagonists (pindolol, WAY100635 and ketanserin) blocked the anxiolytic effect caused by 4-PSQ (50 mg/kg, per oral) in the elevated plus maze (EPM) test. The contribution of the GABAergic system was investigated by pretreatment with pentylenetetrazole (a GABAA receptor antagonist) (PTZ). 4-PSQ diminished the PTZ-induced anxiety, and did not modify the locomotor, exploratory and motor activities of mice. Later, this group of animals was euthanized and the blood was removed to determine the levels of corticosterone, and cerebral cortex and hippocampus to determine the mRNA expression levels of cAMP response element binding protein (CREB), brain derived neurotrophic factor (BDNF) and nuclear factor kappa B (NF-κB), as well as the Na+, K+ ATPase activity and reactive species (RS) levels. 4-PSQ was able to significantly reverse the increase in RS and corticosterone levels, as well as the decrease of CREB and BDNF expression in the cerebral structures and increase of NF-κB expression in the hippocampus. Finally, 4-PSQ restored the Na+, K+ ATPase activity in the cerebral structures evaluated. Here, we showed that the modulation of serotonergic and GABAergic systems, factors related to neurogenesis, oxidative status and Na+, K+ ATPase activity contributes to the anxiolytic effect of 4-PSQ and reinforces the therapeutical potential of this compound for the treatment of anxiety.
Assuntos
Ansiolíticos/administração & dosagem , Ansiedade/fisiopatologia , Quinolinas/administração & dosagem , Receptores de GABA-A/fisiologia , Selênio/administração & dosagem , Serotonina/fisiologia , Animais , Ansiedade/prevenção & controle , Antagonistas de Receptores de GABA-A/administração & dosagem , Masculino , Camundongos , Pindolol/administração & dosagem , Quinolinas/química , Receptores de GABA-A/administração & dosagem , Selênio/química , Antagonistas da Serotonina/administração & dosagemRESUMO
The present study investigated a possible antidepressant-like effect of ((4-tert-butylcyclohexylidene)methyl) (4-methoxystyryl) sulfide (BMMS) by using the forced swimming test (FST) and the tail suspension test (TST) in Swiss mice. The contribution of serotoninergic, glutamatergic and nitrergic systems in the antidepressant-like activity of BMMS was evaluated. We also examined the involvement of monoamine oxidase (MAO)-A, MAO-B and Na+, K+-ATPase activities in prefrontal cortex of mice. BMMS, (0.1-10 mg/kg, intragastrically (i.g.)) and fluoxetine (32 mg/kg, i.g.) decreased the immobility time in the FST and TST. The anti-immobility effect of BMMS (10 mg/kg, i.g.) in the TST was prevented by the pretreatment of mice with WAY100635 (0.1 mg/kg, subcutaneously (s.c.), a 5-HT1A receptor antagonist), ketanserin (5 mg/kg, intraperitoneal (i.p.), a 5-HT2A/2C receptor antagonist), and partially blocked by ondansetron (1 mg/kg, i.p., a 5-HT3 receptor antagonist). The anti-immobility effect of BMMS (10 mg / kg, i.g.) was not avoided by pretreatment with MK-801 (0.01 mg/kg, s.c. a non-competitive N-methyl D-Aspartate (NMDA) receptor) in the TST. Pretreatment with L-arginine (500 mg/kg, i.p., a nitric oxide precursor) reversed partially the reduction in the immobility time elicited by BMMS (10 mg/kg, i.g.) in TST. BMMS altered Na+,K+-ATPase and MAO-A activities in prefrontal cortex of mice, but was not able to change the MAO-B activity. In conclusion, BMMS exerted an antidepressant-like effect in mice and serotonergic and nitrergic systems are involved in the antidepressant-like action of compound. BMMS modulated MAO-A and Na+, K+- ATPase activities in prefrontal cortex of mice.
Assuntos
Antidepressivos/farmacologia , Depressão/tratamento farmacológico , Óxido Nítrico/metabolismo , Serotonina/metabolismo , Estirenos/farmacologia , Sulfetos/farmacologia , Animais , Antidepressivos/uso terapêutico , Arginina/farmacologia , Comportamento Animal/efeitos dos fármacos , Depressão/metabolismo , Modelos Animais de Doenças , Antagonistas de Aminoácidos Excitatórios/farmacologia , Fluoxetina/farmacologia , Fluoxetina/uso terapêutico , Elevação dos Membros Posteriores , Masculino , Camundongos , Monoaminoxidase/metabolismo , Atividade Motora/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Antagonistas da Serotonina/farmacologia , ATPase Trocadora de Sódio-Potássio/metabolismo , Estirenos/uso terapêutico , Sulfetos/uso terapêuticoRESUMO
In this study, Schiff bases of chitosan (CS) were synthesized using citronellal, citral, and their derivatives containing selenium and sulfur. Organoselenium and organosulfur compounds show attractive biological and pharmaceutical activities, which can be beneficial to CS-based materials. From the characterization analyses, it was found that the CS-derivatives containing organoselenium and organosulfur compounds exhibited the highest conversion degrees (23 and 28%). Biological assays were conducted using films prepared by the blending of CS-derivatives and poly(vinyl alcohol). The antimicrobial evaluation indicated that the film prepared with the sulfur-containing CS was the most active against the tested pathogens (Escherichia coli, Staphylococcus aureus, and Candida albicans) since it reduced considerably their counts (42.5%, 17.4%, and 18.7%). Finally, in vivo assays revealed that this film attenuates atopic dermatitis-like symptoms in mice by suppressing the increase of myeloperoxidase (MPO) activity and reactive species (RS) levels induced by 2,4-dinitrochlorobenzene (DNCB). In summary, CS-derivatives containing chalcogens, mainly organosulfur, are potential candidates for biomedical applications such as for the treatment of chronic skin diseases.
Assuntos
Antibacterianos/farmacologia , Materiais Biocompatíveis/farmacologia , Quitosana , Dermatite Atópica/tratamento farmacológico , Compostos Organosselênicos/farmacologia , Bases de Schiff/farmacologia , Animais , Candida albicans/efeitos dos fármacos , Calcogênios/farmacologia , Quitosana/análogos & derivados , Quitosana/farmacologia , Dermatite Atópica/induzido quimicamente , Dinitroclorobenzeno/química , Modelos Animais de Doenças , Escherichia coli/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Peroxidase/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Staphylococcus aureus/efeitos dos fármacosRESUMO
The aim of this study was to evaluate the capacity of conventional irrigation, passive ultrasonic irrigation (PUI), and Easy Clean for removing calcium hydroxide-based root canal dressing from oval root canals. Thirty mandibular uniradicular incisors with oval canals were used, and subjected to chemical-mechanical preparation with Reciproc R40 instruments. The main canal was filled with a paste based on Ca(OH)2 P.A., iodoform and propylene glycol in the ratio of 3:1:1. The teeth were stored in 100% humidity at a temperature of 37°C for 14 days. Afterwards, the teeth were divided into three groups (n = 10) according to the method of irrigation used (conventional irrigation, PUI, and Easy Clean). The specimens were analyzed by computed microtomography at three time intervals: before placing the root canal dressing, with the root canal dressing in place, and after application of the irrigation methods for removing it. The data were submitted to Kruskal-Wallis and Dunn tests for analyzing the canal as a whole, and Friedman and Dunn for analyzing the root thirds. The results showed that conventional irrigation was less efficient for removing the root canal dressing in comparison with the methods that agitated the irrigant solution (p < .05). When the root canal was analyzed as a whole, Easy Clean, and PUI were similar (p > .05). In analysis of the thirds, Easy Clean was more efficient than conventional irrigation in all the thirds, while PUI showed this behavior only in the cervical third (p < .05). The authors concluded that in oval canals, none of the irrigation methods were capable of removing all the root canal dressing, however, the methods that agitated the irrigant solution were more efficient than conventional irrigation.
RESUMO
This study investigated the main effects of the oral treatment with 7-chloro-4-phenylselanyl quinoline (4-PSQ) on symptoms, inflammatory and oxidative parameters in an atopic dermatitis (AD) model in BALB/c mice. In addition, the possibility of antioxidant property of 4-PSQ improves the potential of a biofilm (based on chitosan/poly(vinyl alcohol) (PVA)/ bovine bone powder (BBP)) for the treatment of AD-like skin lesions was evaluated. 2,4-Dinitrochlorobenzene (DNCB) was applied to the dorsal skin on days 1-3 for sensitization. Mice were challenged with DNCB on the ear (on days 14-29) and dorsal skin (on days 14, 17, 20, 23, 26, and 29) and treated with 4-PSQ, dexamethasone, biofilm (biofilm sample without 4-PSQ) or 4-PSQ-loaded biofilms. On the day 30, skin severity scores and scratching behavior were determined. After that, animals were sacrificed, and ears and dorsal skin were removed for determination of inflammatory and oxidative parameters. DNCB induced the skin lesions, scratching behavior and ear swelling, increased myeloperoxidase (MPO) activity (ear and back) and reactive species (RS) levels (back). 4-PSQ, 4-PSQ-loaded biofilms and biofilm treatments ameliorated skin severity scores, scratching behavior and inflammatory response induced by DNCB. 4-PSQ and 4-PSQ-loaded biofilm treatments partially protected against the increase in the RS levels induced by DNCB. Our results revealed that the incorporation of 4-PSQ improved the therapeutic effect of the biofilm. The efficacy of 4-PSQ in treating AD-like lesions was similar or better than dexamethasone. In summary, 4-PSQ has a potential therapeutic advantage in the treatment and management of AD.
Assuntos
Anti-Inflamatórios/farmacologia , Quinolinas/química , Quinolinas/farmacologia , Pele/efeitos dos fármacos , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Antioxidantes/química , Antioxidantes/metabolismo , Comportamento Animal/efeitos dos fármacos , Dermatite Atópica/tratamento farmacológico , Dermatite Atópica/patologia , Dexametasona/farmacologia , Dexametasona/uso terapêutico , Dinitroclorobenzeno/química , Dinitroclorobenzeno/toxicidade , Camundongos , Camundongos Endogâmicos BALB C , Peroxidase/metabolismo , Quinolinas/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Índice de Gravidade de Doença , Pele/metabolismo , Pele/patologia , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
The quinolone compounds have been reported for many biological properties, especially as potent antioxidants. This study investigated the antioxidant effect of 7-chloro-4-phenylselenyl-quinoline (PSQ), a quinolone derivative with organoselenium group, against oxidative stress induced by sodium nitroprusside (SNP) in brains of mice. A second objective was to verify the importance of phenylselenyl group presents at position 4 of the quinoline structure to antioxidant effect of compound. So, it was compared the antioxidant effect of PSQ with a quinoline without organoseleniun group (7-chloroquinoline [QN]). Swiss mice were used and received SNP (0.335 µmol/site, intracerebroventricular) 30â¯min after treatment with PSQ or QN, at the doses of 50â¯mg/kg (intragastrically). After 1â¯h, animals were sacrificed and the brains were removed to biochemistry analysis. Thiobarbituric acid reactive species (TBARS), protein carbonyl (PC) and non-protein thiol (NPSH) levels, as well as catalase (CAT), glutathione S transferase (GST) and δ -aminolevulinic acid (δ-ALA-D) activities were determined. SNP increased TBARS and PC levels, and reduced the enzymatic (CAT and GST activity) and non-enzymatic (NPSH levels) antioxidant defenses and inhibited the δ-ALA-D activity. PSQ avoided the increase in the lipid peroxidation and PC levels, as well as the decrease in the NPSH levels, CAT, GST and δ-ALA-D activities QN partially avoided the increase in lipid peroxidation, but it not protected against alterations induced by SNP. In conclusion, phenylselenyl group present in quinoline structure is critical for antioxidant activity of PSQ.
Assuntos
Antioxidantes/farmacologia , Compostos Organosselênicos/farmacologia , Quinolinas/farmacologia , Ácido Aminolevulínico/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Catalase/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Transferase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Compostos de Sulfidrila/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
We describe here a simple method for the synthesis of 6-arylselanylpurines with antioxidant and anticholinesterase activities, and memory improvement effect. This class of compounds was synthesized in good yields by a reaction of 6-chloropurine with diaryl diselenides using NaBH4 as reducing agent and PEG-400 as solvent. Furthermore, the synthesized compounds were evaluated for their in vitro antioxidant and acetylcholinesterase (AChE) inhibitor activities. The best AChE inhibitor was assessed on the in vivo memory improvement. Our results demonstrated that the 6-((4-chlorophenyl)selanyl)-9H-purine and 6-(p-tolylselanyl)-9H-purine presented in vitro antioxidant effect. In addition, 6-((4-fluorophenyl)selanyl)-9H-purine inhibited the AChE activity and improved memory, being a promising therapeutic agent for the treatment of Alzheimer's disease.
Assuntos
Acetilcolinesterase/metabolismo , Antioxidantes/farmacologia , Inibidores da Colinesterase/farmacologia , Memória/efeitos dos fármacos , Compostos Organosselênicos/farmacologia , Purinas/farmacologia , Doença de Alzheimer/tratamento farmacológico , Animais , Antioxidantes/administração & dosagem , Antioxidantes/química , Inibidores da Colinesterase/administração & dosagem , Inibidores da Colinesterase/síntese química , Relação Dose-Resposta a Droga , Masculino , Camundongos , Estrutura Molecular , Compostos Organosselênicos/administração & dosagem , Compostos Organosselênicos/síntese química , Purinas/administração & dosagem , Purinas/química , Relação Estrutura-AtividadeRESUMO
The aim of the present study was to investigate the effects of SCH58261, a selective adenosine A2A receptor antagonist, on striatal toxicity induced by 3-nitropropionic acid (3-NP) in rats. The experimental protocol consisted of 10 administrations (once a day) of SCH58261 (0.01 or 0.05 mg/kg/day, intraperitoneal, i.p.). From 7th to 10th day, 3-NP (20 mg/kg/day, i.p.) was injected 1 h after SCH58261 administration. Twenty-four hours after the last 3-NP injection, the body weight gain, locomotor activity (open-field test), motor coordination (rotarod test), striatal succinate dehydrogenase (SDH) activity and parameters linked to striatal oxidative status were evaluated in rats. The marked body weight loss resulting from 3-NP injections in rats was partially protected by SCH 58261 at both doses. SCH 58261 at the highest dose was effective against impairments on motor coordination and locomotor activity induced by 3-NP. SCH 58261 was unable to restore the inhibition of SDH activity caused by 3-NP. In addition, the increase in striatal reactive species (RS) levels, depletion of reduced glutathione (GSH) content and stimulation of glutathione reductase (GR) activity provoked by 3-NP injections were alleviated by both doses of SCH 58261. The highest dose of SCH 58261 was also effective in attenuating the increase of protein carbonyl levels as well as the inhibition of glutathione peroxidase (GPx) activity in rats exposed to 3-NP. Our results revealed that reduction of oxidative stress in rat striatum by adenosine A2A receptor antagonism contributes for alleviating 3-NP-induced toxicity.
Assuntos
Antagonistas do Receptor A2 de Adenosina/farmacologia , Corpo Estriado/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Nitrocompostos/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Propionatos/farmacologia , Pirimidinas/farmacologia , Triazóis/farmacologia , Animais , Corpo Estriado/metabolismo , Glutationa/metabolismo , Masculino , Atividade Motora/efeitos dos fármacos , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Teste de Desempenho do Rota-RodRESUMO
The present study investigated the possible effect of BMMS in protecting against memory impairment in an Alzheimer's disease model induced by scopolamine in mice. Another objective was to evaluate the involvement of oxidative stress and Na+/K+ ATPase activity in cerebral cortex and hippocampus of mice. Male Swiss mice were divided into four groups: groups I and III received canola oil (10 ml/kg, intragastrically (i.g.)), while groups II and IV received BMMS (10 mg/kg, i.g.). Thirty minutes after treatments, groups III and IV received scopolamine (1 mg/kg, intraperitoneal (i.p.)), while groups I and II received saline (5 ml/kg, i.p.). Behavioral tests were performed thirty minutes after scopolamine or saline injection. Cerebral cortex and hippocampus were removed to determine the thiobarbituric acid reactive species (TBARS) levels, non-protein thiols (NPSH) content, catalase (CAT) and Na+/K+ ATPase activities. The results showed that BMMS pretreatment protected against the reduction in alternation and latency time induced by scopolamine in the Y-maze test and step-down inhibitory avoidance, respectively. In the Barnes maze, the latency to find the escape box and the number of holes visited were attenuated by BMMS. Locomotor and exploratory activities were similar in all groups. BMMS pretreatment protected against the increase in the TBARS levels, NPSH content and CAT activity, as well as the inhibition on the Na+/K+ ATPase activity caused by scopolamine in the cerebral cortex. In the hippocampus, no significant difference was observed. In conclusion, the present study revealed that BMMS protected against the impairment of retrieval of short-term and long-term memories caused by scopolamine in mice. Moreover, antioxidant effect and protection on the Na+/K+ ATPase activity are involved in the effect of compound against memory impairment in AD model induced by scopolamine.
Assuntos
Antioxidantes/farmacologia , Transtornos da Memória/tratamento farmacológico , Memória/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , ATPase Trocadora de Sódio-Potássio/metabolismo , Sulfetos/farmacologia , Animais , Antioxidantes/uso terapêutico , Catalase/metabolismo , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/metabolismo , Camundongos , Escopolamina , Sulfetos/uso terapêutico , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
Biodiesel industry by-products appear to be an excellent alternative source for ruminant feed and may contribute to increased agricultural activity in terms of productivity and profitability. Among the various by-products, oilseed cakes have great potential for use due to their high protein and lipid contents, which make them an energetic feed source that would fulfill the nutritional requirements of animals. Thus, studies that aim to determine the optimum levels of oilseed cake in ruminant feed are important for maximizing the potential use of these by-products.
El uso de los subproductos de la industria de biodiesel para alimentar a los rumiantes parece ser una excelente alternativa, que puede contribuir al aumento de las actividades agrícolas en términos de productividad y rentabilidad. Entre los sub-productos, las tortas de semillas oleaginosas tienen un gran potencial debido a los importantes niveles de proteínas y lípidos que las caracterizan como alimentos proteicos o energéticos capaces de satisfacer las necesidades nutricionales de los animales. Así, los estudios que tienen como objetivo determinar los niveles óptimos de tortas de semillas oleaginosas en los piensos para rumiantes son importantes para maximizar el uso potencial de estos subproductos.
A utilização de coprodutos oriundos da produção do biodiesel na alimentação de ruminantes surge como alternativa, que pode contribuir para o crescimento das atividades agropecuárias, em termos de produtividade e rentabilidade. Dentre os coprodutos, as tortas apresentam grande potencial, haja vista as consideráveis concentrações de proteína e extrato etéreo, que as caracterizam como alimentos protéicos e/ou energéticos, capazes de permitir o atendimento das exigências nutricionais destas frações pelos animais. Desta forma, é importante a realização de estudos que determinem os níveis ótimos de aplicação das diversas tortas oleaginosas, visando à busca de melhores resultados.
RESUMO
Objetivo: Descrever a prevalência da cárie precoce na infância em crianças de 6 a 36 meses em creches públicas de Caruaru-PE e a sua associação com características da criança, bem como analisar o conhecimento dos pais ou responsáveis sobre saúde bucal. Método: O desenho de estudo foi do tipo transversal. Foram coletadas informações sobre conhecimentos relacionados à saúde bucal, bem como foram examinados às condições dentárias das crianças e através do Sinasc foram coletadas as características da gestação e do peso ao nascer da criança. Para os testes de associação pelo Qui-quadrado (x2) para avaliar o relacionamento entre as variáveis dependentes (ceo-d) e as variáveis independentes, usou-se o Programa Epi-info versão 6.04. Resultados: Do total de 168 crianças estudadas, examinou-se em média 14,65 dentes por criança. Destes 62,3% estavam hígidos e apenas 3,3% cariados; 92,9% dos pais tinham conhecimento de que os dentes de seus filhos eram de leite e sabiam da sua importância; 78,6% já escovavam os dentes dos filhos; 74,4% sabiam como estavam os dentes dos filhos, apesar de apenas 16,2% identificarem cárie dentária e 6,0% relatarem que o filho teve dor de dente. Apenas 12,5% foram ao dentista, sendo 27,3% para revisão e controle. Das 22,6% das crianças que tinham cárie, 79,4% delas consumiam mamadeira noturna, sendo que 40,7% delas a adoçavam; 30,4% consumiam doces entre as refeições aumentando esse consumo aos 25 meses de idade. Conclusão: A cárie dentária aumenta em função da idade, em conseqüência do aumento do número de dentes erupcionados e do consumo de açúcar na dieta.
Purpose: To describe the prevalence early childhood caries in children aged 6 to 36 months attending public day care centers in the city of Caruaru/PE and its association with the children's characteristics, as well as to assess the knowledge of parents/guardians of oral health.Method: A transversal study design was established. Information regarding oral health was collected and the dental conditions of the children were examined. Information regarding the gestational characteristics and the child weight at birth was gathered by meansof Sinasc (System of Information about Liveborn Infants). For the association tests by the chi-square statistical test to evaluate the relationship between the dependent variables (deft) and independent variables, the Epi-info software version 6.04 was used.Results: Out of 168 children enrolled in this study, 14.65 teeth perchildren were evaluated on average. Out of these, 62.3% were sound and only 3.3% were decayed. 92.9% of the parents/guardians were aware that their children had primary teeth and knew their importance. 78.6% used to brush their children's teeth;74.4% knew how their children's teeth were, although only 16.2% identified dental caries and 6% reported that their child had toothache.Only 12.5% had been to the dentist, being 27.3% for routine clinical visit and control. Of the 22.6% children that had dental caries,79.4% were bottle-fed at night; 40.7% of them consumed sugared nursing bottle and 30.4% consumed sweets between meals, this consumption being increased at 25 months of age.Conclusions: The incidence of dental caries increases with age,as a consequence of the increase of the number of erupted teeth and the consumption of sugar in the diet.