RESUMEN
Neurodegenerative diseases (ND) are characterized, especially, by the progressive loss of neurons, resulting in neuropsychomotor dysfunctions. Even with a high prevalence, NDs are treated with drugs that alleviate the symptoms of patients, but which develop adverse events and still do not inhibit the progression of the disease. Thus, within a new pharmacological perspective, this review aimed to verify the therapeutic potential of natural compounds of marine origin against ND. For this, an integrative review was carried out, according to the PRISMA methodology, which included steps such as: search, pre-selection and inclusion of articles. The results described revealed species such as Acaudina malpodioides, Holothuria scabra and Xylaria sp., which presented important evidence in relation to Alzheimer's, reducing the generation of ROS, presenting neuroprotective effects and reducing the concentration of Aß peptide. Regarding Parkinson's disease (PD), another example of ND, the bioactive compounds from Holothuria scabra and Xylaria sp., showed to be able to reduce the degeneration of dopaminergic neurons, reduce the deposition of alpha synuclein and reduce the formation of Mutant Huntingtin protein (Mhtt). The other marine compounds and bioactive substances are also described in this review. In conclusion, the evaluated studies indicate that compounds of marine origin emerge as a promising source of bioactive compounds, revealing an important therapeutic potential for the treatment of ND.
Asunto(s)
Productos Biológicos , Enfermedades Neurodegenerativas , Fármacos Neuroprotectores , Enfermedad de Parkinson , Humanos , Neuronas Dopaminérgicas/metabolismo , Enfermedades Neurodegenerativas/tratamiento farmacológico , Enfermedades Neurodegenerativas/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Fármacos Neuroprotectores/metabolismo , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo , Productos Biológicos/farmacología , Animales , Organismos AcuáticosRESUMEN
Neurodegenerative diseases (ND) are characterized, especially, by the progressive loss of neurons, resulting in neuropsychomotor dysfunctions. Even with a high prevalence, NDs are treated with drugs that alleviate the symptoms of patients, but which develop adverse events and still do not inhibit the progression of the disease. Thus, within a new pharmacological perspective, this review aimed to verify the therapeutic potential of natural compounds of marine origin against ND. For this, an integrative review was carried out, according to the PRISMA methodology, which included steps such as: search, pre-selection and inclusion of articles. The results described revealed species such as Acaudina malpodioides, Holothuria scabra and Xylaria sp., which presented important evidence in relation to Alzheimer's, reducing the generation of ROS, presenting neuroprotective effects and reducing the concentration of Aß peptide. Regarding Parkinson's disease (PD), another example of ND, the bioactive compounds from Holothuria scabra and Xylaria sp., showed to be able to reduce the degeneration of dopaminergic neurons, reduce the deposition of alpha synuclein and reduce the formation of Mutant Huntingtin protein (Mhtt). The other marine compounds and bioactive substances are also described in this review. In conclusion, the evaluated studies indicate that compounds of marine origin emerge as a promising source of bioactive compounds, revealing an important therapeutic potential for the treatment of ND.
As doenças neurodegenerativas (ND) são caracterizadas, especialmente, pela perda progressiva de neurônios, resultando em disfunções neuropsicomotoras. Mesmo apresentando uma alta prevalência, as DN são tratadas com medicamentos que aliviam os sintomas dos pacientes, mas que desenvolvem eventos adversos e ainda não inibem a progressão da doença. Assim, dentro de uma nova perspectiva farmacológica, esta revisão teve como objetivo verificar o potencial terapêutico de compostos naturais de origem marinha frente às DN. Para tal, foi realizada uma revisão integrativa, segundo a metodologia PRISMA que compreendeu etapas como: busca, pré-seleção e inclusão dos artigos. Os resultados descritos revelaram espécies como, Acaudina malpodioides, Holothuria scabra e Xylaria sp., que apresentaram importantes evidências em relação ao Alzheimer, reduzindo a geração de ROS, apresentando efeitos neuroprotetores e reduzindo a concentração de peptídeo Aß. Sobre a doença de Parkinson (PD), outro exemplo de ND, os compostos bioativos da Holothuria scabra e da Xylaria sp., mostraram ser capazes de diminuir a degeneração de neurônios dopaminérgicos, reduzir a deposição de alfa sinucleína e reduzir a formação de agregados da proteína Huntingtina mutante (Mhtt). Os outros compostos marinhos e substâncias bioativas também são descritos nesta revisão. Em conclusão, os estudos avaliados indicam que os compostos de origem marinha despontam como uma promissora fonte de compostos bioativos, revelando um importante potencial terapêutico para o tratamento das ND.
Asunto(s)
Pepinos de Mar/química , Fauna Marina , Fármacos Neuroprotectores/análisis , Enfermedades Neurodegenerativas/terapiaRESUMEN
This study evaluated the effect of pH on the microstructure of cream cheese and compared pH-induced changes in its microstructure with concomitant changes in cheese firmness and meltability. On 4 different days, experimental batches of cultured hot pack cream cheese were manufactured and analyzed for initial chemical composition. The cheeses were then sectioned into samples that were randomly assigned to 7 different treatment groups. Three groups were exposed to ammonia vapor for 1, 3, and 5 min to increase the pH; 3 groups were exposed to acetic acid vapor for 30, 60, and 90 min to decrease the pH; and 1 unexposed group served as the control. After equilibration at 4 degrees C, samples were analyzed for pH, firmness, meltability, and microstructure by scanning electron microscopy. The effects of experimental treatments on cheese pH, firmness, and meltability were analyzed by randomized complete block analysis of variance (ANOVA). Relationships between cheese pH and firmness and meltability were evaluated by regression. Experimental treatments significantly affected cheese pH, firmness, and meltability. Cheese firmness decreased and meltability increased with increasing pH from about pH 4.2 to 6.8. Cheese microstructure also changed dramatically over the same approximate pH range. Specifically, the volume of the protein network surrounding the fat droplets increased markedly with increasing pH, presumably due to casein swelling. These data support the hypothesis that protein-to-water interactions increased as the cheese pH increased, which gave rise to progressive swelling of the casein network, softer texture, and increased meltability.
Asunto(s)
Queso/análisis , Concentración de Iones de Hidrógeno , Amoníaco , Queso/clasificación , Manipulación de Alimentos , Conservación de Alimentos , Microscopía Electrónica de RastreoRESUMEN
Rats fed a high-fructose diet represent an animal model for insulin resistance and hypertension. We recently showed that a high-fructose diet containing vegetable oil but a normal sodium/potassium ratio induced mild insulin resistance with decreased insulin receptor substrate-1 tyrosine phosphorylation in the liver and muscle of normal rats. In the present study, we examined the mean blood pressure, serum lipid levels and insulin sensitivity by estimating in vivo insulin activity using the 15-min intravenous insulin tolerance test (ITT, 0.5 ml of 6 æg insulin, iv) followed by calculation of the rate constant for plasma glucose disappearance (Kitt) in male Wistar-Hannover rats (110-130 g) randomly divided into four diet groups: control, 1:3 sodium/potassium ratio (R Na:K) diet (C 1:3 R Na:K); control, 1:1 sodium/potassium ratio diet (CNa 1:1 R Na:K); high-fructose, 1:3 sodium/potassium ratio diet (F 1:3 R Na:K), and high-fructose, 1:1 sodium/potassium ratio diet (FNa 1:1 R Na:K) for 28 days. The change in R Na:K for the control and high-fructose diets had no effect on insulin sensitivity measured by ITT. In contrast, the 1:1 R Na:K increased blood pressure in rats receiving the control and high-fructose diets from 117 + or - 3 and 118 + or - 3 mmHg to 141 + or - 4 and 132 + or - 4 mmHg (P<0.05), respectively. Triacylglycerol levels were higher in both groups treated with a high-fructose diet when compared to controls (C 1:3 R Na:K: 1.2 + or - 0.1 mmol/l vs F 1:3 R Na:K: 2.3 + or - 0.4 mmol/l and CNa 1:1 R Na:K: 1.2 + or - 0.2 mmol/l vs FNa 1:1 R Na:K: 2.6 + or - 0.4 mmol/l, P<0.05). These data suggest that fructose alone does not induce hyperinsulinemia or hypertension in rats fed a normal R Na:K diet, whereas an elevation of sodium in the diet may contribute to the elevated blood pressure in this animal model
Asunto(s)
Animales , Masculino , Ratas , Presión Sanguínea , Dieta , Fructosa/fisiología , Resistencia a la Insulina , Glucemia/análisis , Hiperinsulinismo/etiología , Hipertensión/etiología , Hipertrigliceridemia/etiología , Lípidos/sangre , Potasio/administración & dosificación , Ratas Wistar , Sodio/administración & dosificaciónRESUMEN
Rats fed a high-fructose diet represent an animal model for insulin resistance and hypertension. We recently showed that a high-fructose diet containing vegetable oil but a normal sodium/potassium ratio induced mild insulin resistance with decreased insulin receptor substrate-1 tyrosine phosphorylation in the liver and muscle of normal rats. In the present study, we examined the mean blood pressure, serum lipid levels and insulin sensitivity by estimating in vivo insulin activity using the 15-min intravenous insulin tolerance test (ITT, 0.5 ml of 6 microg insulin, iv) followed by calculation of the rate constant for plasma glucose disappearance (Kitt) in male Wistar-Hannover rats (110-130 g) randomly divided into four diet groups: control, 1:3 sodium/potassium ratio (R Na:K) diet (C 1:3 R Na:K); control, 1:1 sodium/potassium ratio diet (CNa 1:1 R Na:K); high-fructose, 1:3 sodium/potassium ratio diet (F 1:3 R Na:K), and high-fructose, 1:1 sodium/potassium ratio diet (FNa 1:1 R Na:K) for 28 days. The change in R Na:K for the control and high-fructose diets had no effect on insulin sensitivity measured by ITT. In contrast, the 1:1 R Na:K increased blood pressure in rats receiving the control and high-fructose diets from 117 +/- 3 and 118 +/- 3 mmHg to 141 +/- 4 and 132 +/- 4 mmHg (P < 0.05), respectively. Triacylglycerol levels were higher in both groups treated with a high-fructose diet when compared to controls (C 1:3 R Na:K: 1.2 +/- 0.1 mmol/l vs F 1:3 R Na:K: 2.3 +/- 0.4 mmol/l and CNa 1:1 R Na:K: 1.2 +/- 0.2 mmol/l vs FNa 1:1 R Na:K: 2.6 +/- 0.4 mmol/l, P < 0.05). These data suggest that fructose alone does not induce hyperinsulinemia or hypertension in rats fed a normal R Na:K diet, whereas an elevation of sodium in the diet may contribute to the elevated blood pressure in this animal model.
Asunto(s)
Presión Sanguínea/efectos de los fármacos , Dieta , Fructosa/farmacología , Síndrome Metabólico , Animales , Glucemia/análisis , Fructosa/administración & dosificación , Hiperinsulinismo/etiología , Hipertensión/etiología , Hipertrigliceridemia/etiología , Lípidos/sangre , Masculino , Potasio/administración & dosificación , Ratas , Ratas Wistar , Sodio en la Dieta/administración & dosificaciónRESUMEN
Insulin stimulates the tyrosine kinase activity of its receptor resulting in the tyrosine phosphorylation of pp185, which contains insulin receptor substrates IRS-1 and IRS-2. These early steps in insulin action are essential for the metabolic effects of insulin. Feeding animals a high-fructose diet results in insulin resistance. However, the exact molecular mechanism underlying this effect is unknown. In the present study, we determined the levels and phosphorylation status of the insulin receptor and pp185 (IRS-(1/2)) in liver and muscle of rats submitted to a high-fructose diet evaluated by immunoblotting with specific antibodies. Feeding fructose (28 days) induced a discrete insulin resistance, as demonstrated by the insulin tolerance test. Plasma glucose and serum insulin and cholesterol levels of the two groups of rats, fructose-fed and control, were similar, whereas plasma triacylglycerol concentration was significantly increased in the rats submitted to the fructose diet (P<0.05). There were no changes in insulin receptor concentration in the liver or muscle of either group. However, insulin-stimulated receptor autophosphorylation was reduced to 72 +/- 4% (P<0.05) in the liver of high-fructose rats. The IRS-1 protein levels were similar in both liver and muscle of the two groups of rats. In contrast, there was a significant decrease in insulin-induced pp185 (IRS-(1/2)) phosphorylation, to 83 +/- 5% (P<0.05) in liver and to 77 +/- 4% (P<0.05) in muscle of the high-fructose rats. These data suggest that changes in the early steps of insulin signal transduction may have an important role in the insulin resistance induced by high-fructose feeding.
Asunto(s)
Fructosa/efectos adversos , Resistencia a la Insulina , Hígado/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Fosfoproteínas/metabolismo , Animales , Modelos Animales de Enfermedad , Fructosa/administración & dosificación , Intolerancia a la Glucosa/metabolismo , Proteínas Sustrato del Receptor de Insulina , Hígado/metabolismo , Masculino , Músculo Esquelético/metabolismo , Fosforilación , Ratas , Ratas WistarRESUMEN
Insulin stimulates the tyrosine kinase activity of its receptor resulting in the tyrosine phosphorylation of pp185, which contains insulin receptor substrates IRS-1 and IRS-2. These early steps in insulin action are essential for the metabolic effects of insulin. Feeding animals a high-fructose diet results in insulin resistance. However, the exact molecular mechanism underlying this effect is unknown. In the present study, we determined the levels and phosphorylation status of the insulin receptor and pp185 (IRS-1/2) in liver and muscle of rats submitted to a high-fructose diet evaluated by immunoblotting with specific antibodies. Feeding fructose (28 days) induced a discrete insulin resistance, as demonstrated by the insulin tolerance test. Plasma glucose and serum insulin and cholesterol levels of the two groups of rats, fructose-fed and control, were similar, whereas plasma triacylglycerol concentration was significantly increased in the rats submitted to the fructose diet (P<0.05). There were no changes in insulin receptor concentration in the liver or muscle of either group. However, insulin-stimulated receptor autophosphorylation was reduced to 72 + or - 4 percent (P<0.05) in the liver of high-fructose rats. The IRS-1 protein levels were similar in both liver and muscle of the two groups of rats. In contrast, there was a significant decrease in insulin-induced pp185 (IRS-1/2) phosphorylation, to 83 + or - 5 percent (P<0.05) in liver and to 77 + or - 4 percent (P<0.05) in muscle of the high-fructose rats. These data suggest that changes in the early steps of insulin signal transduction may have an important role in the insulin resistance induced by high-fructose feeding
Asunto(s)
Animales , Ratas , Masculino , Fructosa/efectos adversos , Hígado/efectos de los fármacos , Músculos/efectos de los fármacos , Receptor de Insulina/análisis , Modelos Animales de Enfermedad , Intolerancia a la Glucosa/metabolismo , Resistencia a la Insulina , Fosforilación , Ratas WistarRESUMEN
A high fructose diet induces insulin resistance in rats, although the exact molecular mechanism involved is unknown. In this study, we used immunoprecipitation and immunoblotting to examine the levels and phosphorylation status of the insulin receptor (IR) and insulin receptor substrate-1 (IRS-1), as well as the association of the IRS-1 with phosphatidylinositol 3-kinase (PI 3-kinase), and phosphotyrosine phosphatase (SHP2) in the liver and muscle of rats fed a control or high fructose diet for 28 d. There were no differences in IR and the IRS-1 protein levels in the liver and muscle of rats fed the control and high fructose diets. However, tyrosine-phosphorylation of the insulin receptor after insulin stimulation was reduced to 71 +/- 2% (P < 0.05) of control in the liver of the fructose-fed rats. In samples previously immunoprecipitated with anti-IRS-1 antibody and blotted with antiphosphotyrosine antibody, the insulin-stimulated IRS-1 phosphorylation levels in the liver and muscle of the fructose-fed group were only 70 +/- 6% (P < 0.05) and 76 +/- 5% (P < 0.05) of those of control rats, respectively. The insulin-stimulated IRS-1 association with PI 3-kinase was reduced to 84 +/- 3% (P < 0.05) in the liver and to 84 +/- 4% (P < 0.05) in the muscle of the fructose-fed group compared with control rats. Insulin-stimulated IRS-1 association with SHP2 was reduced to 79 +/- 5% (P < 0.05) in liver of the fructose-fed rats. These data suggest that changes in the early steps of insulin signal transduction may have an important role in the insulin resistance observed in these rats.
Asunto(s)
Carbohidratos de la Dieta/farmacología , Fructosa/farmacología , Insulina/metabolismo , Hígado/efectos de los fármacos , Músculo Esquelético/efectos de los fármacos , Receptor de Insulina/efectos de los fármacos , Animales , Glucemia/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Carbohidratos de la Dieta/administración & dosificación , Fructosa/administración & dosificación , Proteínas Sustrato del Receptor de Insulina , Hígado/enzimología , Hígado/metabolismo , Masculino , Músculo Esquelético/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfoproteínas/efectos de los fármacos , Fosfoproteínas/metabolismo , Fosforilación/efectos de los fármacos , Proteínas Tirosina Fosfatasas/metabolismo , Ratas , Ratas Wistar , Receptor de Insulina/metabolismoRESUMEN
Mices with different ages ranging 1 to 60 days old were inoculated with thermostable (ST) enterotoxin of Escherichia coli, either by intragastric injection through the abdominal wall or by intubation. Doses were proportional to body weight and values obtained for intestines/carcass weight ratios (RI/C) of inoculated mice showed that mice remained susceptible to the enterotoxin up to 16 days old, with RI/C values equal or greater than 0.085. Older mice were completely resistant to ST activity as RI/C values demonstrated. Histological observations showed that whole gut's fixation of inoculated mice was absolutely necessary since any handling of intestinal loops evoked artifactual alterations. Even though, alterations were found, probably of mechanical nature, caused by intestinal distension consequent to the increased fluid volume into gut's lumen. These alterations did not differ from those observed for both cholera and LT-E. coli enterotoxins, characterized by lymphatic and blood vascular dilatation within mucosae lamina propria, eventually shrinkage of lamna propria just below the epithelium as well epithelial's vacuolizations.