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Métodos Terapéuticos y Terapias MTCI
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1.
Pharmacol Biochem Behav ; 122: 53-60, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24650588

RESUMEN

Lectins recognize and reversibly bind to carbohydrates attached to proteins and lipids modulating a variety of signaling pathways. We previously showed that ConBr, a lectin from Canavalia brasiliensis seeds, produced an antidepressant-like effect in mice by modulating the monoaminergic neurotransmitter systems. Moreover, ConBr blocked hippocampal neurotoxicity induced by quinolinic acid in vivo and by glutamate in vitro, suggesting a neuroprotective activity of ConBr via glutamatergic system modulation. Therefore, the present study was undertaken to investigate the involvement of the N-methyl-D-aspartate (NMDA) receptor and the L-arginine-nitric oxide (NO) pathway in the antidepressant-like action displayed by ConBr in the forced swimming test (FST). With the aim of verifying the involvement of NMDA receptors in the antidepressant-like effect of ConBr (10 µg/site, i.c.v.), an intracerebroventricular (i.c.v.) pretreatment with either NMDA (0.1 pmol/site) or D-serine (30 µg/site) was carried out. The results show that both treatments blocked the effect of ConBr. Furthermore, the coadministration of subeffective doses of the NMDA receptor antagonist MK-801 (0.001 mg/kg, i.p.) or ketamine (0.1 mg/kg, i.p.; NMDA receptor antagonist) and ConBr (0.1 µg/site, i.c.v.) caused a synergistic reduction in immobility time. In order to verify the dependence of the L-arginine-NO-cGMP pathway, on the effect of ConBr in the FST, a pretreatment with the NO precursor, L-arginine (750 mg/kg, i.p.), or the PDE5 inhibitor, sildenafil (5 mg/kg, i.p.), was performed. Both drugs abolished the antidepressant-like action of ConBr. Finally, the administration of subeffective doses of the soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 30 pmol/site, i.c.v.) and ConBr (0.1 µg/site, i.c.v.) produced a synergistic antidepressant-like effect in the FST. Taken together, the results suggest that the antidepressant-like effect of ConBr in the FST involves NMDA receptor inhibition and reduction in NO and cGMP synthesis.


Asunto(s)
Antidepresivos/uso terapéutico , Canavalia , Ácido Glutámico , Extractos Vegetales/uso terapéutico , Lectinas de Plantas/uso terapéutico , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Animales , Antidepresivos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Ácido Glutámico/fisiología , Masculino , Ratones , Extractos Vegetales/aislamiento & purificación , Lectinas de Plantas/aislamiento & purificación , Receptores de N-Metil-D-Aspartato/fisiología , Semillas , Resultado del Tratamiento
2.
Cell Biochem Funct ; 31(8): 636-42, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23316007

RESUMEN

Long-chain polyunsaturated n-3 fatty acids (n-3 LCPUFAs) have hypolipidemic effects and modulate intermediary metabolism to prevent or reverse insulin resistance in a way that is not completely elucidated. Here, effects of these fatty acids on the lipid profile, phosphoenolpyruvate carboxykinase (PEPCK) activity, lipid synthesis from glucose in epididymal adipose tissue (Ep-AT) and liver were investigated. Male rats were fed a high-sucrose diet (SU diet), containing either sunflower oil or a mixture of sunflower and fish oil (SU-FO diet), and the control group was fed a standard diet. After 13 weeks, liver, adipose tissue and blood were harvested and analysed. The dietary n-3 LCPUFAs prevented sucrose-induced increase in adiposity and serum free fat acids, serum and hepatic triacylglycerol and insulin levels. Furthermore, these n-3 LCPUFAs decreased lipid synthesis from glucose and increased PEPCK activity in the Ep-AT of rats fed the SU-FO diet compared to those fed the SU diet, besides reducing lipid synthesis from glucose in hepatic tissue. Thus, the inclusion of n-3 LCPUFAs in the diet may be beneficial for the prevention or attenuation of dyslipidemia and insulin resistance, and for reducing the risk of related chronic diseases.


Asunto(s)
Tejido Adiposo/metabolismo , Sacarosa en la Dieta/administración & dosificación , Ácidos Grasos Omega-3/administración & dosificación , Ácidos Grasos Omega-3/farmacología , Glucosa/metabolismo , Lípidos/biosíntesis , Fosfoenolpiruvato Carboxiquinasa (ATP)/metabolismo , Tejido Adiposo/efectos de los fármacos , Animales , Sacarosa en la Dieta/farmacología , Suplementos Dietéticos , Activación Enzimática/efectos de los fármacos , Glucosa/química , Masculino , Ratas , Ratas Wistar
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