RESUMO
This study evaluated the effects of omega-3 polyunsaturated fatty acids (PUFAs) on oxidative stress and energy metabolism parameters in the visceral fat of a high-fat-diet induced obesity model. Energy intake, body mass, and visceral fat mass were also evaluated. Male Swiss mice received either a control diet (control group) or a high-fat diet (obese group) for 6 weeks. After this period, the groups were divided into control + saline, control + omega-3, obese + saline, and obese + omega-3, and to these groups 400 mg·(kg body mass)-1·day-1 of fish oil (or saline) was administered orally, for 4 weeks. Energy intake and body mass were monitored throughout the experiment. In the 10th week, the animals were euthanized and the visceral fat (mesenteric) was removed. Treatment with omega-3 PUFAs did not affect energy intake or body mass, but it did reduced visceral fat mass. In visceral fat, omega-3 PUFAs reduced oxidative damage and alleviated changes to the antioxidant defense system and the Krebs cycle. The mitochondrial respiratory chain was neither altered by obesity nor by omega-3 PUFAs. In conclusion, omega-3 PUFAs have beneficial effects on the visceral fat of obese mice because they mitigate changes caused by the consumption of a high-fat diet.
Assuntos
Modelos Animais de Doenças , Ácidos Graxos Ômega-3/farmacologia , Gordura Intra-Abdominal/efeitos dos fármacos , Obesidade/tratamento farmacológico , Animais , Dieta Hiperlipídica , Metabolismo Energético/efeitos dos fármacos , Gordura Intra-Abdominal/metabolismo , Masculino , Camundongos , Obesidade/induzido quimicamente , Estresse Oxidativo/efeitos dos fármacosRESUMO
The aim of this study was to assess inflammatory parameters, oxidative stress and energy metabolism in the hypothalamus of diet-induced obese mice. Male Swiss mice were divided into two study groups: control group and obese group. The animals in the control group were fed a diet with adequate amounts of macronutrients (normal-lipid diet), whereas the animals in the obese group were fed a high-fat diet to induce obesity. Obesity induction lasted 10 weeks, at the end of this period the disease model was validated in animals. The animals in the obese group had higher calorie consumption, higher body weight and higher weight of mesenteric fat compared to control group. Obesity showed an increase in levels of interleukin 1ß and decreased levels of interleukin 10 in the hypothalamus. Furthermore, increased lipid peroxidation and protein carbonylation, and decreased level of glutathione in the hypothalamus of obese animals. However, there was no statistically significant difference in the activity of antioxidant enzymes, superoxide dismutase and catalase. The obese group had lower activity of complex I, II and IV of the mitochondrial respiratory chain, as well as lower activity of creatine kinase in the hypothalamus as compared to the control group. Thus, the results from this study showed changes in inflammatory markers, and dysregulation of metabolic enzymes in the pathophysiology of obesity.
Assuntos
Dieta Hiperlipídica/efeitos adversos , Metabolismo Energético/fisiologia , Hipotálamo/metabolismo , Obesidade/metabolismo , Animais , Antioxidantes/farmacologia , Biomarcadores/metabolismo , Ingestão de Energia/efeitos dos fármacos , Inflamação/metabolismo , Masculino , Camundongos , Neuroquímica/métodos , Estresse Oxidativo/efeitos dos fármacosRESUMO
This study evaluated the effects of omega-3 on inflammation, oxidative stress, and energy metabolism parameters in the brain of mice subjected to high-fat diet-induced obesity model. Body weight and visceral fat weight were evaluated as well. Male Swiss mice were divided into control (purified low-fat diet) and obese (purified high-fat diet). After 6 weeks, the groups were divided into control + saline, control + omega-3, obese + saline, and obese + OMEGA-3. Fish oil (400 mg/kg/day) or saline solution was administrated orally, during 4 weeks. When the experiment completed 10 weeks, the animals were euthanized and the brain and visceral fat were removed. The brain structures (hypothalamus, hippocampus, prefrontal cortex, and striatum) were isolated. Treatment with omega-3 had no effect on body weight, but reduced the visceral fat. Obese animals showed increased inflammation, increased oxidative damage, decreased antioxidant enzymes activity and levels, changes in the Krebs cycle enzyme activities, and inhibition of mitochondrial respiratory chain complexes in the brain structures. Omega-3 treatment partially reversed the changes in the inflammatory and in the oxidative damage parameters and attenuated the alterations in the antioxidant defense and in the energy metabolism (Krebs cycle and mitochondrial respiratory chain). Omega-3 had a beneficial effect on the brain of obese animals, as it partially reversed the changes caused by the consumption of a high-fat diet and consequent obesity. Our results support studies that indicate omega-3 may contribute to obesity treatment.
Assuntos
Encéfalo/patologia , Ácidos Graxos Ômega-3/uso terapêutico , Obesidade/tratamento farmacológico , Obesidade/patologia , Animais , Antioxidantes/farmacologia , Peso Corporal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Dieta Hiperlipídica , Modelos Animais de Doenças , Transporte de Elétrons/efeitos dos fármacos , Ácidos Graxos Ômega-3/farmacologia , Inflamação/patologia , Gordura Intra-Abdominal/patologia , Masculino , Camundongos , Camundongos Obesos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Obesidade/induzido quimicamente , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacosRESUMO
RESUMO Objetivo: Analisar o perfil de utilização de medicamentos em crianças de zero a cinco anos de idade. Métodos: Estudo transversal baseado em entrevistas realizadas em domicílio com cuidadores (pais, tios ou avós) das crianças cadastradas em dez unidades de Estratégia Saúde da Família (ESF), distribuídas em diferentes pontos geográficos do município de Tubarão, Santa Catarina. Resultados: Foram entrevistados 350 cuidadores, cujas crianças sorteadas possuíam, em média, 2,6 anos de idade. Destas, 56,9% utilizaram, pelo menos, um medicamento nos 15 dias anteriores à entrevista, sendo que 31,1% foram expostas à automedicação e 35,7% utilizaram, pelo menos, um medicamento obtido por prescrição atual. O uso de medicamentos foi associado à faixa etária de até 24 meses, consulta periódica com pediatra e diagnóstico de doenças agudas e doenças crônicas. Entre as crianças medicadas, 19,1% foram expostas a pelo menos um medicamento de forma inadequada (considerando dose, intervalo entre doses ou período de tratamento). Quanto ao armazenamento, 55,2% dos medicamentos estavam guardados em lugar inseguro, ou seja, ao acesso das crianças, e 32,0% em locais inadequados, por estarem expostos a luz, calor ou umidade. Ainda, 45,2% estavam sem bula, 38,9% sem embalagem secundária e 1,6% fora do prazo de validade. Conclusões: As crianças estudadas apresentam uma frequência elevada de uso de medicamentos, devendo ser incentivadas ações que visem ao uso seguro e racional de fármacos nessa população.
ABSTRACT Objective: To analyze the context of drug use in children aged zero to five years old. Methods: Cross-sectional study based on interviews conducted at home with caregivers (parents, uncles or grandparents) of the children enrolled in ten Family Health Strategy units across different geographical points of the city of Tubarão, Santa Catarina, Brazil. Results: A total of 350 caregivers were interviewed, whose children's mean age was 2.6 years. Of these, 56.9% had used at least one drug in the 15 days prior to the interview, 31.1% had been exposed to self-medication and 35.7% had used at least one medication obtained by current prescription. The use of medication was associated with the age range up to 24 months, periodic consultation with pediatricians and diagnosis of chronic and acute diseases. Among medicated children, 19.1% inappropriately had been exposed to at least one medication (considering dose, dose interval or period of treatment). Regarding medication storage, 55.2% of interviewees stored them in unsafe places that could be accessed by children and 32.0% in inappropriate places, with exposure to light, heat or humidity. Moreover, 45.2% of the interviewees stored drugs out of their packages, 38.9% without secondary packaging, and 1.6% of drugs had expired date. Conclusions: Drug use is high among children in this age range, and actions aimed at the safe and rational use of these substances in this population should be encouraged.
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Uso de Medicamentos/estatística & dados numéricos , Brasil , Estudos Transversais , FarmacoepidemiologiaRESUMO
OBJECTIVE: To analyze the context of drug use in children aged zero to five years old. METHODS: Cross-sectional study based on interviews conducted at home with caregivers (parents, uncles or grandparents) of the children enrolled in ten Family Health Strategy units across different geographical points of the city of Tubarão, Santa Catarina, Brazil. RESULTS: A total of 350 caregivers were interviewed, whose children's mean age was 2.6 years. Of these, 56.9% had used at least one drug in the 15 days prior to the interview, 31.1% had been exposed to self-medication and 35.7% had used at least one medication obtained by current prescription. The use of medication was associated with the age range up to 24 months, periodic consultation with pediatricians and diagnosis of chronic and acute diseases. Among medicated children, 19.1% inappropriately had been exposed to at least one medication (considering dose, dose interval or period of treatment). Regarding medication storage, 55.2% of interviewees stored them in unsafe places that could be accessed by children and 32.0% in inappropriate places, with exposure to light, heat or humidity. Moreover, 45.2% of the interviewees stored drugs out of their packages, 38.9% without secondary packaging, and 1.6% of drugs had expired date. CONCLUSIONS: Drug use is high among children in this age range, and actions aimed at the safe and rational use of these substances in this population should be encouraged.
OBJETIVO: Analisar o perfil de utilização de medicamentos em crianças de zero a cinco anos de idade. MÉTODOS: Estudo transversal baseado em entrevistas realizadas em domicílio com cuidadores (pais, tios ou avós) das crianças cadastradas em dez unidades de Estratégia Saúde da Família (ESF), distribuídas em diferentes pontos geográficos do município de Tubarão, Santa Catarina. RESULTADOS: Foram entrevistados 350 cuidadores, cujas crianças sorteadas possuíam, em média, 2,6 anos de idade. Destas, 56,9% utilizaram, pelo menos, um medicamento nos 15 dias anteriores à entrevista, sendo que 31,1% foram expostas à automedicação e 35,7% utilizaram, pelo menos, um medicamento obtido por prescrição atual. O uso de medicamentos foi associado à faixa etária de até 24 meses, consulta periódica com pediatra e diagnóstico de doenças agudas e doenças crônicas. Entre as crianças medicadas, 19,1% foram expostas a pelo menos um medicamento de forma inadequada (considerando dose, intervalo entre doses ou período de tratamento). Quanto ao armazenamento, 55,2% dos medicamentos estavam guardados em lugar inseguro, ou seja, ao acesso das crianças, e 32,0% em locais inadequados, por estarem expostos a luz, calor ou umidade. Ainda, 45,2% estavam sem bula, 38,9% sem embalagem secundária e 1,6% fora do prazo de validade. CONCLUSÕES: As crianças estudadas apresentam uma frequência elevada de uso de medicamentos, devendo ser incentivadas ações que visem ao uso seguro e racional de fármacos nessa população.
Assuntos
Uso de Medicamentos/estatística & dados numéricos , Brasil , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , FarmacoepidemiologiaRESUMO
Neurological dysfunction as a result of neuroinflammation has been reported in sepsis and cause high mortality. High levels of cytokines stimulate the formation of neurotoxic metabolites by kynurenine (KYN) pathway. Vitamin B6 (vit B6) has anti-inflammatory and antioxidant properties and also acts as a cofactor for enzymes of the KYN pathway. Thus, by using a relevant animal model of polymicrobial sepsis, we studied the effect of vit B6 on the KYN pathway, acute neurochemical and neuroinflammatory parameters, and cognitive dysfunction in rats. Male Wistar rats (250-300 g) were submitted to cecal ligation and perforation (CLP) and divided into sham + saline, sham + vit B6, CLP + saline, and CLP + vit B6 (600 mg/kg, s.c.) groups. Twenty-four hours later, the prefrontal cortex and hippocampus were removed for neurochemical and neuroinflammatory analyses. Animals were followed for 10 days to determine survival rate, when cognitive function was assessed by behavioral tests. Vitamin B6 interfered in the activation of kynurenine pathway, which led to an improvement in neurochemical and neuroinflammatory parameters and, consequently, in the cognitive functions of septic animals. Thus, the results indicate that vit B6 exerts neuroprotective effects in acute and late consequences after sepsis.
Assuntos
Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Cinurenina/metabolismo , Sepse/tratamento farmacológico , Sepse/microbiologia , Vitamina B 6/uso terapêutico , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Disfunção Cognitiva/patologia , Citocinas/metabolismo , Metabolismo Energético/efeitos dos fármacos , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Estimativa de Kaplan-Meier , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Nitratos/metabolismo , Nitritos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Permeabilidade , Peroxidase/metabolismo , Carbonilação Proteica/efeitos dos fármacos , Ratos Wistar , Triptofano/metabolismo , Vitamina B 6/farmacologiaRESUMO
Liraglutide is a human glucagon-like peptide-1 (GLP-1) analogue that was recently approved to treat obesity in some countries. Considering that liraglutide effects on brain energy metabolism are little known, we evaluated the effects of liraglutide on the energy metabolism. Animals received a single or daily injection of saline or liraglutide during 7 days (25, 50, 100, or 300 µg/kg i.p.). Twenty-four hours after the single or last injection, the rats were euthanized and the hypothalamus, prefrontal cortex, cerebellum, hippocampus, striatum, and posterior cortex were isolated. Our results demonstrated that a single dose of liraglutide in young rats increased the activity of complexes and inhibited creatine kinase activity. Repeated administrations of liraglutide in young rats reduced the activity of complexes and activated creatine kinase activity. In adult rats, a single dose of liraglutide reduced the activity of complex I and creatine kinase and increased the activity of complexes II and IV. Repeated administrations of liraglutide in adult rats increased the activity of complexes I and IV and reduced the activity of complex II and creatine kinase. We concluded that liraglutide may interfere in energy metabolism, because analysis of different times of administrations, concentrations, and level of brain development leads to divergent results.
Assuntos
Encéfalo/metabolismo , Metabolismo Energético/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Liraglutida/farmacologia , Envelhecimento , Animais , Encéfalo/efeitos dos fármacos , Creatina Quinase/metabolismo , Relação Dose-Resposta a Droga , Complexo I de Transporte de Elétrons/metabolismo , Complexo II de Transporte de Elétrons/metabolismo , Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Humanos , Hipoglicemiantes/administração & dosagem , Liraglutida/administração & dosagem , Masculino , Ratos , Ratos WistarRESUMO
Currently, obesity and its associated complications are considered major public health problems worldwide. Because the causes are multifactorial and complex, different treatment methods are used, which include diet and exercise, as well as the use of drugs, although they can have adverse side effects. A new target for the treatment of obesity may be the incretin system, which consists of hormones that seem to contribute to weight loss. In this sense, some studies have shown a relationship between weight loss and drugs related to incretin system, including glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors. The objective of this review is to summarize the association between the incretin system and obesity treatment.
Assuntos
Fármacos Antiobesidade/uso terapêutico , Incretinas/uso terapêutico , Obesidade/tratamento farmacológico , Animais , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Peptídeo 1 Semelhante ao Glucagon/agonistas , Humanos , Incretinas/fisiologia , Obesidade/fisiopatologia , Receptores dos Hormônios Gastrointestinais/agonistas , Receptores dos Hormônios Gastrointestinais/antagonistas & inibidoresRESUMO
Major depression is a heterogeneous psychiatric disorder whose pathophysiology is not clearly established yet. Some studies have shown that oxidative stress and mitochondrial dysfunction are involved in the development of major depression. Since most depressed patients do not achieve complete remission of symptoms, new therapeutic alternatives are needed and omega-3 has been highlighted in this scenario. Therefore, we have investigated the effects of omega-3 on behavioral and biochemical parameters in rats submitted to chronic mild stress (CMS). Male Wistar rats were submitted to CMS for 40 days. After the CMS period, we administered a 500 mg/kg dose of omega-3 orally, once a day, for 7 days. The animals submitted to CMS presented anhedonia, had no significant weight gain, presented increased levels of lipid peroxidation and protein carbonylation, and inhibition of complex I and IV activities of the mitochondrial respiratory chain. The treatment with omega-3 did not reverse anhedonia; however, it reversed weight change, increased lipid peroxidation and protein carbonylation levels, and partially reversed the inhibition of mitochondrial respiratory chain complexes. The findings support studies that state that major depression is associated with mitochondrial dysfunction and oxidative stress, and that omega-3 supplementation could reverse some of these changes, probably due to its antioxidant properties.
Assuntos
Anedonia/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Ácidos Graxos Ômega-3/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Psicológico/metabolismo , Anedonia/fisiologia , Animais , Comportamento Animal/fisiologia , Peso Corporal/efeitos dos fármacos , Peso Corporal/fisiologia , Encéfalo/metabolismo , Transtorno Depressivo Maior/metabolismo , Modelos Animais de Doenças , Complexo I de Transporte de Elétrons/metabolismo , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/fisiologia , Ratos , Ratos WistarRESUMO
Studies have consistently reported the participation of oxidative stress, energetic metabolism impairment, and creatine kinase (CK) activity alterations in rat brain in early times in an animal model of sepsis and persist for up to 10 days. We have assessed the antioxidant effects of administration of Ebselen (Eb) e diphenyl diselenide (PhSe)2 two organoselenium compounds on brain oxidative stress, energetic metabolism, and CK activity 12, 24 h, and 10 days after sepsis by cecal ligation and perforation (CLP) in rats. Male Wistar rats underwent either sham operation or CLP and were treated with oral injection of Eb (50 mg/kg) or (PhSe)2 (50 mg/kg) or vehicle. 12, 24 h, and 10 days after CLP, the rats were sacrificed, and samples from brain (hippocampus, striatum, cerebellum, prefrontal cortex, and cortex) were obtained and assayed for thiobarbituric acid reactive species and protein carbonyls formation, mitochondrial respiratory chain, and CK activity. We observed in the results a reduction of oxidative damage to lipids and proteins in the different cerebral structures studied and times with the administration of (PhSe)2; however, Eb seems to exert the same effect. Such changes are reflected in the assessment of mitochondrial respiratory chain complexes by reversing the decreased activity of the complex caused by the model of CLP and CK activity. Our data provide the first experimental demonstration that (PhSe)2 was able to reduce the brain dysfunction associated with CLP-induced sepsis in rats, by decreasing oxidative stress parameters mitochondrial dysfunction and CK activity in early times and in late time.