Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 4 de 4
Filtrar
1.
Metab Brain Dis ; 32(2): 519-528, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-27987060

RESUMEN

Studies have shown that oxidative stress is involved in the pathophysiology of bipolar disorder (BD). It is suggested that omega-3 (ω3) fatty acids are fundamental to maintaining the functional integrity of the central nervous system. The animal model used in this study displayed fenproporex-induced hyperactivity, a symptom similar to manic BD. Our results showed that the administration of fenproporex, in the prevent treatment protocol, increased lipid peroxidation in the prefrontal cortex (143%), hippocampus (58%) and striatum (181%), and ω3 fatty acids alone prevented this change in the prefrontal cortex and hippocampus, whereas the co-administration of ω3 fatty acids with VPA prevented the lipoperoxidation in all analyzed brain areas, and the co-administration of ω3 fatty acids with Li prevented this increase only in the prefrontal cortex and striatum. Moreover, superoxide dismutase (SOD) activity was decreased in the striatum (54%) in the prevention treatment, and the administration of ω3 fatty acids alone or in combination with Li and VPA partially prevented this inhibition. On the other hand, in the reversal treatment protocol, the administration of fenproporex increased carbonyl content in the prefrontal cortex (25%), hippocampus (114%) and striatum (91%), and in prefrontal coxter the administration of ω3 fatty acids alone or in combination with Li and VPA reversed this change, whereas in the hippocampus and striatum only ω3 fatty acids alone or in combination with VPA reversed this effect. Additionally, the administration of fenproporex resulted in a marked increase of TBARS in the hippocampus and striatum, and ω3 fatty acids alone or in combination with Li and VPA reversed this change. Finally, fenproporex administration decreased SOD activity in the prefrontal cortex (85%), hippocampus (52%) and striatum (76%), and the ω3 fatty acids in combination with VPA reversed this change in the prefrontal cortex and striatum, while the co-administration of ω3 fatty acids with Li reversed this inhibition in the hippocampus and striatum. In conclusion, our results support other studies showing the importance of ω3 fatty acids in the brain and the potential for these fatty acids to aid in the treatment of BD.


Asunto(s)
Anfetaminas/toxicidad , Antimaníacos/uso terapéutico , Depresores del Apetito/toxicidad , Conducta Animal/efectos de los fármacos , Ácidos Grasos Omega-3/uso terapéutico , Hipercinesia/psicología , Estrés Oxidativo/efectos de los fármacos , Animales , Química Encefálica/efectos de los fármacos , Hipercinesia/inducido químicamente , Hipercinesia/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Carbonato de Litio/uso terapéutico , Masculino , Carbonilación Proteica/efectos de los fármacos , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Ácido Valproico/uso terapéutico
2.
Metab Brain Dis ; 30(1): 215-21, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25252880

RESUMEN

Tyrosinemia type II is an inborn error of metabolism caused by a deficiency in hepatic cytosolic aminotransferase. Affected patients usually present a variable degree of mental retardation, which may be related to the level of plasma tyrosine. In the present study we evaluated effect of chronic administration of L-tyrosine on the activities of citrate synthase, malate dehydrogenase, succinate dehydrogenase and complexes I, II, II-III and IV in cerebral cortex, hippocampus and striatum of rats in development. Chronic administration consisted of L-tyrosine (500 mg/kg) or saline injections 12 h apart for 24 days in Wistar rats (7 days old); rats were killed 12 h after last injection. Our results demonstrated that L-tyrosine inhibited the activity of citrate synthase in the hippocampus and striatum, malate dehydrogenase activity was increased in striatum and succinate dehydrogenase, complexes I and II-III activities were inhibited in striatum. However, complex IV activity was increased in hippocampus and inhibited in striatum. By these findings, we suggest that repeated administrations of L-tyrosine cause alterations in energy metabolism, which may be similar to the acute administration in brain of infant rats. Taking together the present findings and evidence from the literature, we hypothesize that energy metabolism impairment could be considered an important pathophysiological mechanism underlying the brain damage observed in patients with tyrosinemia type II.


Asunto(s)
Química Encefálica/efectos de los fármacos , Metabolismo Energético/efectos de los fármacos , Tirosina/toxicidad , Tirosinemias , Animales , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/enzimología , Citrato (si)-Sintasa/análisis , Citrato (si)-Sintasa/antagonistas & inhibidores , Ciclo del Ácido Cítrico/efectos de los fármacos , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/enzimología , Modelos Animales de Enfermedad , Proteínas del Complejo de Cadena de Transporte de Electrón/análisis , Proteínas del Complejo de Cadena de Transporte de Electrón/efectos de los fármacos , Hipocampo/efectos de los fármacos , Hipocampo/enzimología , Malato Deshidrogenasa/análisis , Malato Deshidrogenasa/efectos de los fármacos , Masculino , Proteínas del Tejido Nervioso/análisis , Ratas , Ratas Wistar
3.
Mediators Inflamm ; 2014: 582197, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25147439

RESUMEN

Palmitoleic acid (PMA) has anti-inflammatory and antidiabetic activities. Here we tested whether these effects of PMA on glucose homeostasis and liver inflammation, in mice fed with high-fat diet (HFD), are PPAR-α dependent. C57BL6 wild-type (WT) and PPAR-α-knockout (KO) mice fed with a standard diet (SD) or HFD for 12 weeks were treated after the 10th week with oleic acid (OLA, 300 mg/kg of b.w.) or PMA 300 mg/kg of b.w. Steatosis induced by HFD was associated with liver inflammation only in the KO mice, as shown by the increased hepatic levels of IL1-beta, IL-12, and TNF-α; however, the HFD increased the expression of TLR4 and decreased the expression of IL1-Ra in both genotypes. Treatment with palmitoleate markedly attenuated the insulin resistance induced by the HFD, increased glucose uptake and incorporation into muscle in vitro, reduced the serum levels of AST in WT mice, decreased the hepatic levels of IL1-beta and IL-12 in KO mice, reduced the expression of TLR-4 and increased the expression of IL-1Ra in WT mice, and reduced the phosphorylation of NF ����B (p65) in the livers of KO mice. We conclude that palmitoleate attenuates diet-induced insulin resistance, liver inflammation, and damage through mechanisms that do not depend on PPAR-α.


Asunto(s)
Ácidos Grasos Monoinsaturados/uso terapéutico , PPAR alfa/metabolismo , Animales , Western Blotting , Dieta Alta en Grasa/efectos adversos , Ensayo de Inmunoadsorción Enzimática , Resistencia a la Insulina , Interleucina-12 , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Ácido Oléico/metabolismo , Ácido Oléico/uso terapéutico , PPAR alfa/deficiencia , PPAR alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo
4.
Mol Neurobiol ; 54(6): 3935-3947, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-27246566

RESUMEN

Studies have shown that changes in energy metabolism are involved in the pathophysiology of bipolar disorder (BD). It was suggested that omega-3 (ω3) fatty acids have beneficial properties in the central nervous system and that this fatty acid plays an important role in energy metabolism. Therefore, the study aimed to evaluate the effect of ω3 fatty acids alone and in combination with lithium (Li) or valproate (VPA) on behaviour and parameters of energy metabolism in an animal model of mania induced by fenproporex. Our results showed that co-administration of ω3 fatty acids and Li was able to prevent and reverse the increase in locomotor and exploratory activity induced by fenproporex. The combination of ω3 fatty acids with VPA was only able to prevent the fenproporex-induced hyperactivity. For the energy metabolism parameters, our results showed that the administration of Fen for the reversal or prevention protocol inhibited the activities of succinate dehydrogenase, complex II and complex IV in the hippocampus. However, hippocampal creatine kinase (CK) activity was decreased only for the reversal protocol. The ω3 fatty acids, alone and in combination with VPA or Li, prevented and reversed the decrease in complex II, IV and succinate dehydrogenase activity, whereas the decrease in CK activity was only reversed after the co-administration of ω3 fatty acids and VPA. In conclusion, our results showed that the ω3 fatty acids combined with VPA or Li were able to prevent and reverse manic-like hyperactivity and the inhibition of energy metabolism in the hippocampus, suggesting that ω3 fatty acids may play an important role in the modulation of behavioural parameters and energy metabolism.


Asunto(s)
Antimaníacos/uso terapéutico , Conducta Animal , Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/metabolismo , Metabolismo Energético/efectos de los fármacos , Ácidos Grasos Omega-3/uso terapéutico , Anfetaminas , Animales , Antimaníacos/farmacología , Trastorno Bipolar/inducido químicamente , Trastorno Bipolar/genética , Citrato (si)-Sintasa/metabolismo , Creatina Quinasa/metabolismo , Modelos Animales de Enfermedad , Ácidos Grasos Omega-3/administración & dosificación , Ácidos Grasos Omega-3/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Litio/administración & dosificación , Litio/farmacología , Litio/uso terapéutico , Masculino , Ratas Wistar , Succinato Deshidrogenasa/metabolismo , Ácido Valproico/administración & dosificación , Ácido Valproico/farmacología , Ácido Valproico/uso terapéutico
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA