RESUMO
Haloperidol is a widely used antipsychotic, despite the severe motor side effects associated with its chronic use. This study was carried out to compare oral dyskinesia induced by different formulations of haloperidol-loaded nanocapsules containing caprylic/capric triglycerides, fish oil or grape seed oil (GSO) as core, as well as free haloperidol. Haloperidol-loaded lipid-core nanocapsules formulations were prepared, physicochemical characterized and administered (0.5 mg kg-1-ip) to rats for 28 days. Oral dyskinesia was evaluated acutely and subchronically and after that cell viability and free radical generation in cortex and substantia nigra. All formulations presented satisfactory physicochemical parameters. Acutely, all formulations were able to prevent oral dyskinesia development in comparison to free haloperidol, except haloperidol-loaded nanocapsules containing GSO, whose effect was only partial. After subchronic treatment, all haloperidol-loaded nanocapsules formulations prevented oral dyskinesia in relation to free drug. Also, haloperidol-loaded nanocapsules containing fish oil and GSO were more effective than caprylic/capric triglycerides nanocapsules and free haloperidol in cell viability preservation and control of free radical generation. Our findings showed that fish oil formulation may be considered as the best formulation of haloperidol-loaded lipid-core nanocapsules, being able to prevent motor side effects associated with chronic use of antipsychotic drugs, as haloperidol.
Assuntos
Antidiscinéticos/farmacologia , Discinesias/tratamento farmacológico , Óleos de Peixe/química , Haloperidol/farmacologia , Nanocápsulas/uso terapêutico , Óleos de Plantas/química , Vitis/química , Animais , Produtos Biológicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Discinesias/metabolismo , Peixes , Masculino , Ratos WistarRESUMO
BACKGROUND: Pruritus and discomfort are often present in patients with xerosis and atopic dermatitis. Several studies suggest an important role of diet in skin pathophysiology. OBJECTIVE: This study evaluated the effect of dietary fatty acids in the skin physiology via an itch-related animal model with and without supplementation with fish oil (FO), a source of polyunsaturated fatty acids (PUFA), especially omega 3 (n-3). METHODS: Male Wistar rats were divided into two groups-non-supplemented (control) and supplemented with FO (3g/kg/day) by gavage for 90 days. Every 30 days, scratching and skin parameters (transepidermal water loss (TEWL), hydration, and local blood flow) were evaluated before and after dorsal skin exposure to acetone to induce the itch-related dry skin. At the end of the study, animals were sacrificed, and skin samples collected for fatty acids composition analysis by GC-FID. RESULTS: FO supplementation reduced the TEWL and increased the skin hydration, with significant changes from day 60 on, while skin microcirculation registered no changes. It also alleviated the acetone induced skin barrier alteration, revealed by a faster resolution of TEWL and hydration, and elimination of itch-related scratching induced by dry skin. These changes were associated with the shift in the skin fatty acids incorporation pattern (richer in n-3 with n-6/n-3<5) resulting from the FO supplementation. CONCLUSION: Skin barrier dynamics seem to be influenced by FO n-3 PUFA, with suppressive effects on the scratching behaviour induced by dry skin. Hence, long-term supplementation with n-3 PUFA rich nutrients might reinforce and restore cutaneous integrity and function.
Assuntos
Óleos de Peixe/farmacologia , Dermatopatias/tratamento farmacológico , Fenômenos Fisiológicos da Pele/efeitos dos fármacos , Pele/química , Acetona , Administração Oral , Animais , Comportamento Animal/efeitos dos fármacos , Suplementos Nutricionais , Modelos Animais de Doenças , Ácidos Graxos Ômega-3/análise , Ácidos Graxos Ômega-3/farmacologia , Masculino , Prurido/induzido quimicamente , Prurido/tratamento farmacológico , Prurido/fisiopatologia , Ratos , Ratos Wistar , Pele/irrigação sanguínea , Pele/efeitos dos fármacos , Dermatopatias/induzido quimicamente , Dermatopatias/fisiopatologia , Água/análise , Perda Insensível de ÁguaRESUMO
O objetivo do presente estudo foi avaliar o efeito da aspersão de extratos de Lippia alba na estabilidade lipídica de filés de carpa húngara armazenados a -18±2°C. Filés não tratados (controle sem aspersão) ou aspergidos (1mL 10g-1 de filé) com água destilada (controle água destilada) ou com extratos de L. alba (0,10g mL-1) hidrometanólico ou aquoso foram analisados durante o armazenamento nos dias zero, 90 e 180. Independente do tempo de congelamento, o extrato hidrometanólico reduziu os valores de dienos conjugados (DC) dos filés em relação aos demais tratamentos, além de reduzir os valores de ácidos graxos livres aos 90 dias (P<0,05). O extrato aquoso resultou em maior teor de peróxidos após 180 dias de congelamento comparado aos demais tratamentos (P<0,05). Os extratos hidrometanólico e aquoso reduziram os valores de substâncias reativas ao ácido tiobarbitúrico (TBARS) após 180 dias, comparados aos filés tratados com água destilada e sem aspersão (P<0,05). Ambos os extratos de L. alba retardaram a oxidação lipídica, sendo que o extrato aquoso retardou a degradação de produtos primários da oxidação lipídica (peróxidos) em produtos secundários (TBARS), enquanto o extrato hidrometanólico parece ser mais eficiente, pois inibiu de forma similar tanto a formação de DC e peróxidos, quanto a sua degradação em produtos secundários (TBARS).
The effect of sprinkling with Lippia alba extracts was evaluated on the lipid stability of common carp fillets stored at -18±2°C. Fillets that received no treatment (no spray control) or that were sprayed (1mL 10g-1 fillet) with distilled water (water control) or with hydro-methanolic or aqueous extract of L. alba (0.10g mL-1) were evaluated immediately (time zero) and after 90 and 180 days. Regardless of the storage time, the hydro-methanolic extract reduced the conjugated dienes (CD) values of fillets compared to the other treatments, and reduced the free fatty acid levels at 90 days (P<0.05). The aqueous extract caused higher peroxide value after 180 days of frozen storage compared to the other treatments (P<0.05). The hydro-methanolic and aqueous extracts reduced thiobarbituric acid reactive substances (TBARS) values after 180 days compared to the non-treated fillets or to the water-sprayed fillets (P<0.05). Both extracts have delayed lipid oxidation. While the aqueous L. alba extract delayed the degradation of primary oxidation products (peroxides) into secondary products (TBARS), the hydro-methanolic extract was more efficient as it inhibited both the CD and peroxide formation and its degradation into secondary products (TBARS).
RESUMO
The influence of trans fatty acids (TFA) on lipid profile, oxidative damage and mitochondrial function in the skin of rats exposed to ultraviolet radiation (UVR) was assessed. The first-generation offspring of female Wistar rats supplemented from pregnancy with either soybean oil (C-SO, rich in n-6 FA; control group) or hydrogenated vegetable fat (HVF, rich in TFA) were continued with the same supplements until adulthood, when half of each group was exposed to UVR for 12 weeks. The HVF group showed higher TFA cutaneous incorporation, increased protein carbonyl (PC) levels, decreased functionality of mitochondrial enzymes and antioxidant defenses of the skin. After UVR, the HVF group showed increased skin thickness and reactive species (RS) generation, with decreased skin antioxidant defenses. RS generation was positively correlated with skin thickness, wrinkles and PC levels. Once incorporated to skin, TFA make it more susceptible to developing UVR-induced disorders.
Assuntos
Suplementos Nutricionais , Mitocôndrias/efeitos dos fármacos , Óleos de Plantas/administração & dosagem , Envelhecimento da Pele/efeitos dos fármacos , Pele/efeitos dos fármacos , Óleo de Soja/administração & dosagem , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Feminino , Hidrogenação , Mitocôndrias/efeitos da radiação , Gravidez , Carbonilação Proteica/efeitos dos fármacos , Carbonilação Proteica/efeitos da radiação , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Pele/química , Pele/metabolismo , Pele/efeitos da radiação , Envelhecimento da Pele/efeitos da radiação , Superóxido Dismutase/metabolismo , Raios UltravioletaRESUMO
Recently, we have described the influence of dietary fatty acids (FA) on mania-like behavior of first generation animals. Here, two sequential generations of female rats were supplemented with soybean oil (SO, rich in n-6 FA, control group), fish oil (FO, rich in n-3 FA) and hydrogenated vegetable fat (HVF, rich in trans FA) from pregnancy and during lactation. In adulthood, half of each group was exposed to an amphetamine (AMPH)-induced mania animal model for behavioral, biochemical and molecular assessments. FO supplementation was associated with lower reactive species (RS) generation and protein carbonyl (PC) levels and increased dopamine transporter (DAT) levels, while HVF increased RS and PC levels, thus decreasing catalase (CAT) activity and DAT levels in hippocampus after AMPH treatment. AMPH impaired short- (1 h) and long- (24 h) term memory in the HVF group. AMPH exposure was able to reduce hippocampal BDNF- mRNA expression, which was increased in FO. While HVF was related to higher trans FA (TFA) incorporation in hippocampus, FO was associated with increased percentage of n-3 polyunsaturated FA (PUFA) together with lower n-6/n-3 PUFA ratio. Interestingly, our data showed a positive correlation between brain-derived neurotrophic factor (BDNF) mRNA and short- and long-term memory (r(2) = 0.53; P = 0.000/r(2) = 0.32; P = 0.011, respectively), as well as a negative correlation between PC and DAT levels (r(2) = 0.23; P = 0.015). Our findings confirm that provision of n-3 or TFA during development over two generations is able to change the neuronal membrane lipid composition, protecting or impairing the hippocampus, respectively, thus affecting neurothrophic factor expression such as BDNF mRNA. In this context, chronic consumption of trans fats over two generations can facilitate the development of mania-like behavior, so leading to memory impairment and emotionality, which are related to neuropsychiatric conditions.
Assuntos
Transtorno Bipolar/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hipocampo/metabolismo , Efeitos Tardios da Exposição Pré-Natal , RNA Mensageiro/metabolismo , Ácidos Graxos trans/toxicidade , Animais , Transtorno Bipolar/psicologia , Modelos Animais de Doenças , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Feminino , Óleos de Peixe/toxicidade , Lactação , Masculino , Transtornos da Memória/metabolismo , Gravidez , Ratos Wistar , Reconhecimento Psicológico/fisiologia , Óleo de Soja/toxicidade , Produtos Vegetais/toxicidadeRESUMO
This study investigated the effects of hydroethanolic E. japonica seed extracts (EJSE) as inhibitors of lipid and protein oxidation on fish pates subjected to refrigerated storage. Five fish pate formulations were developed. These formulations included two control pates (water-control and ascorbic acid-control) and three pates with added EJSE (0.1, 0.2 and 0.4g of seed 100g-1 product, equivalent to 3.4, 6.8 or 13.6mg phenolic compounds kg-1 product), which were then stored under refrigeration for 35 days. Conjugated dienes (CD) and peroxide (PV) values increased along with the storage time; however, these values decreased and were similar among all samples at the end of 35 days of analysis (P<0.05). However, the thiobarbituric acid reactive substances levels (TBARS) did not change along the storage and were not affected by the EJSE. Additionally, there was a linear increase in the protein carbonyl content of fish pates over the storage period (P<0.05), but no effect of EJSE on protein oxidation. The results show that, at the concentrations evaluated, hydroethanolic E. japonica seed extract was unable to inhibit or reduce lipid and protein oxidation in fish pates, but the observed phenolic content emphasizes the need for further studies on the wastes of this fruit.
Este trabalho investigou os efeitos do extrato hidroetanólico de semente de E. japonica (EJSE) como inibidor da oxidação lipídica e proteica em patês a base de pescado armazenados refrigerados. Foram desenvolvidas cinco formulações de patê de pescado. Estas formulações incluíram dois patês controles (controle-água e controle-ácido ascórbico) e três adicionados de EJSE (0,1; 0,2 e 0,4g de semente 100g-1 de produto, equivalente a 3,4; 6,8 ou 13,6mg compostos fenólicos kg-1 de produto) que foram armazenados refrigerados durante 35 dias. Os valores de dienos conjugados (CD) e peróxidos (PV) aumentaram ao longo do armazenamento, contudo, CD e PV diminuíram de maneira semelhante em todas as amostras aos 35 dias de análise (P<0,05). No entanto, o conteúdo de substâncias reativas ao ácido tiobarbitúrico (TBARS) não se modificou ao longo do armazenamento e não foi afetado pelo EJSE. Também houve aumento linear no conteúdo de proteínas carboniladas dos patês de pescado ao longo do armazenamento (P<0,05), sem efeito do EJSE na oxidação proteica. Os resultados mostram que, nas concentrações avaliadas, o extrato hidroetanólico de semente de E. japonica não foi capaz de inibir ou reduzir as oxidações lipídicas e proteicas em patês de pescado, mas seu conteúdo fenólico enfatiza para a necessidade de aprofundar as pesquisas com o resíduo desta fruta.
RESUMO
The current Western diet often provides considerable amounts of saturated and trans fatty acids (TFA), whose incorporation into neuronal membranes has been implicated in changes of brain neurochemical functions. Such influence has caused concerns due to precipitation of neuropsychiatric disorders, whose data are still unclear. Here we evaluated the influence of different fats on preference parameters for amphetamine (AMPH): adolescent rats were orally supplemented with soybean oil (SO, rich in n-6 FA, which was considered an isocaloric control group), fish oil (FO, rich in n-3 FA) and hydrogenated vegetable fat (HVF, rich in saturated and trans FA) from weaning, which were born of dams supplemented with the same fat from pregnancy and lactation. AMPH preference, anxiety-like symptoms and locomotor index were evaluated in conditioned place preference (CPP), elevated plus maze (EPM) and open-field (OF), respectively, while brain oxidative status was determined in cortex, striatum and hippocampus. HVF increased AMPH-CPP and was associated with withdrawal signs, as observed by increased anxiety-like symptoms. Moreover, SO and FO were not associated with AMPH preference, but only FO-supplemented rats did not show any anxiety-like symptoms or increased locomotion. FO supplementation was related to lower oxidative damages to proteins and increased CAT activity in striatum and hippocampus, as well as increased GSH levels in blood, while HVF was related to increased oxidative status. In conclusion, our study showed the harmful influence of TFA on AMPH-CPP and drug craving symptoms, which can be related to dopaminergic neurotransmission.
Assuntos
Anfetamina/farmacologia , Comportamento Animal/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/farmacologia , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos trans/farmacologia , Animais , Condicionamento Clássico , Feminino , Ratos , Ratos WistarRESUMO
Os pequenos frutos estão em evidência por seu potencial de industrialização e também pela presença de compostos antioxidantes. Recentes pesquisas estão, aos poucos, desvendando os pequenos frutos e suas vantagens à saúde humana. A soma desse conhecimento e do potencial que o Brasil tem em produzir esses frutos vem incentivar o consumo destes e novas pesquisas, o que pode, consequentemente, aumentar a proteção contra os efeitos deletérios dos radicais livres. Em função disso, esta revisão discute a relação do potencial antioxidante da amora, framboesa, morango e seu benefício à saúde. Pode-se concluir que a variedade de compostos existentes nos pequenos frutos, além da multiplicidade genética, edafoclimática, métodos de processamento e acondicionamento dos pequenos frutos estudados, confere amplo e diferenciado espectro de capacidade antioxidante a esses, conferindo-os efeitos antiprolifereativos e anticarcinogênicos. Com isto, percebe-se a razão da crescente industrialização e o motivo do estímulo ao consumo dos pequenos frutos em questão.