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Oncotarget ; 8(15): 25552-25563, 2017 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-28424423


The antidepressant-like effect of trans-astaxanthin, a compound present rich in algae, was evaluated through behavioral and neurochemical methods. Results showed that trans-astaxanthin treatment significantly decreased the immobility time in force swim test and tail suspension test, but did not influence locomotor activity. Trans-astaxanthin treatment did not effectively antagonize hypothermia and ptosis induced by reserpine. However, pre-treatment with para-chlorophenylalanine abolished the anti-immobility effect of trans-astaxanthin in force swim and tail suspension test. These results suggested that the mechanism of antidepressant-like effect of trans-astaxanthin may involve the serotonergic system, but not noradrenaline system. This hypothesis was confirmed by neurochemical assays which showed that trans-astaxanthin increased serotonin levels in the hippocampus, frontal cortex, striatum and hypothalamus. Furthermore, our data suggested that trans-astaxanthin decreased indoleamine 2, 3-dioxygenase activity in the hippocampus, frontal cortex and hypothalamus. Inhibition of indoleamine 2,3-dioxygenase activity subsequently decreased the kynurenine/tryptophan ratio and increased the serotonin/tryptophan ratio in these brain regions. Taken together, these findings indicate that the antidepressant-like effect of trans-astaxanthin involves the serotonergic system.

Antidepressivos/farmacologia , Atividade Motora/efeitos dos fármacos , Neurônios Serotoninérgicos/efeitos dos fármacos , Neurônios Serotoninérgicos/metabolismo , Serotonina/metabolismo , Animais , Comportamento Animal , Monoaminas Biogênicas/metabolismo , Encéfalo/metabolismo , Ativação Enzimática/efeitos dos fármacos , Expressão Gênica , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Masculino , Camundongos , Monoaminoxidase/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Triptofano/metabolismo , Xantofilas/farmacologia
Bosn J Basic Med Sci ; 17(1): 12-16, 2017 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-27968708


Cerebral infarction is a type of ischemic stroke and is one of the main causes of irreversible brain damage. Although multiple neuroprotective agents have been investigated recently, the potential of DL-2-amino-3-phosphonopropionic acid (DL-AP3) in treating oxygen-glucose deprivation (OGD)-induced neuronal injury, has not been clarified yet. This study was aimed to explore the role of DL-AP3 in primary neuronal cell cultures. Primary neurons were divided into four groups: (1) a control group that was not treated; (2) DL-AP3 group treated with 10 µM of DL-AP3; (3) OGD group, in which neurons were cultured under OGD conditions; and (4) OGD + DL-AP3 group, in which OGD model was first established and then the cells were treated with 10 µM of DL-AP3. Neuronal viability and apoptosis were measured using Cell Counting Kit-8 and flow cytometry. Expressions of phospho-Akt1 (p-Akt1) and cytochrome c were detected using Western blot. The results showed that DL-AP3 did not affect neuronal viability and apoptosis in DL-AP3 group, nor it changed p-Akt1 and cytochrome c expression (p > 0.05). In OGD + DL-AP3 group, DL-AP3 significantly attenuated the inhibitory effects of OGD on neuronal viability (p < 0.001), and reduced OGD induced apoptosis (p < 0.01). Additionally, the down-regulation of p-Akt1 and up-regulation of cytochrome c, induced by OGD, were recovered to some extent after DL-AP3 treatment (p < 0.05 or p < 0.001). Overall, DL-AP3 could protect primary neurons from OGD-induced injury by affecting the viability and apoptosis of neurons, and by regulating the expressions of p-Akt1 and cytochrome c.

Alanina/análogos & derivados , Glucose/química , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/química , Oxigênio/química , Alanina/química , Animais , Apoptose , Infarto Encefálico/patologia , Sobrevivência Celular , Células Cultivadas , Citocromos c/metabolismo , Regulação para Baixo , Feminino , Citometria de Fluxo , Neurônios/metabolismo , Cultura Primária de Células , Ratos , Ratos Sprague-Dawley
J Physiol Sci ; 60(5): 317-24, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20658215


Visfatin (also known as nicotinamide phosphoribosyltransferase and pre-B cell colony-enhancing factor) is a multifunctional protein. Visfatin has been reported to be involved in several biological processes in the cardiovascular system, . However, the role of visfatin in hypertension is still unclear. In this study, we examined the circulating and local adipose visfatin levels in spontaneously hypertensive rats (SHR), stroke-prone spontaneously hypertensive rats (SHR-SP), and in their normotensive control Wistar-Kyoto (WKY). SHR and SHR-SP rats exhibited lower body weight, lower fat tissue and hypolipidemia. No differences of serum visfatin levels were observed in SHR/SHR-SP and WKY. Serum visfatin levels did not correlate to serum glucose, lipids, insulin, and fat pad weights, but significantly correlated to weights of skeletal muscle. Visfatin expression in visceral fat tissue was slightly lower in SHR-SP compared with that in WKY. Moreover, there were no significant differences of visfatin expression in skeletal muscles among WKY, SHR and SHR-SP. Finally, visfatin protein was detected in L6 rat skeletal muscle cell culture medium, indicating that visfatin was secreted from skeletal muscle cells. Thus, our results may provide useful information for understanding the characteristic of visfatin in hypertensive models, and support the view that visfatin may be a myokine.

Tecido Adiposo/química , Hipertensão/sangue , Nicotinamida Fosforribosiltransferase/sangue , Acidente Vascular Cerebral/sangue , Animais , Glicemia/fisiologia , Pressão Sanguínea/fisiologia , Peso Corporal , Frequência Cardíaca , Hipertensão/fisiopatologia , Insulina/sangue , Lipídeos/sangue , Masculino , Músculo Esquelético/fisiologia , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Acidente Vascular Cerebral/fisiopatologia
Clin Exp Pharmacol Physiol ; 37(9): 894-9, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20456420


1. Visfatin (also known as nicotinamide phosphoribosyltransferase or Nampt) is a novel adipokine associated with metabolic abnormalities in obesity and diabetes. The aim of the present study was to determine whether visfatin levels in the circulation and visfatin expression in fat tissues are altered in Lyon hypertensive (LH) rats, a hypertensive strain with numerous metabolic abnormalities, and, if so, to explore the possible correlations between blood visfatin levels and the metabolic abnormalities in LH rats. 2. Male 18-20-week-old LH rats and their control, Lyon normotensive (LN) rats, were used. Blood pressure was recorded in conscious, unrestrained rats. Fat tissue weight was determined. Serum visfatin concentrations were determined by enzyme immunoassay, whereas visfatin expression in fat tissues was determined by western blotting. Relationships between two parameters were evaluated by linear regression analysis. 3. The LH rats had significantly higher bodyweight and fat tissue weight compared with LN rats. Serum lipid levels of total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C) and triglyceride (TG) were all significantly higher in LH rats than in LN rats. Moreover, serum visfatin levels were higher in LH rats than in LN rats and were positively correlated with bodyweight, fat tissue weight and serum lipid levels (i.e. TC, HDL-C, LDL-C, TG and the TG:HDL-C ratio). There were no significant differences in serum glucose and insulin concentrations, or in the whole-body insulin resistance index, between LN and LH rats, and serum visfatin levels were not correlated with any of these parameters. Visfatin expression in visceral fat tissue, but not in subcutaneous fat tissue, was markedly upregulated in LH compared with LN rats. 4. In conclusion, the results of the present study demonstrate that serum visfatin levels in LH rats are elevated and are associated with lipid metabolic abnormalities.

Adipocinas/sangue , Hipertensão/metabolismo , Transtornos do Metabolismo dos Lipídeos/sangue , Nicotinamida Fosforribosiltransferase/sangue , Adipocinas/metabolismo , Tecido Adiposo/metabolismo , Animais , Glicemia/metabolismo , Índice de Massa Corporal , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/metabolismo , Hipertensão/fisiopatologia , Insulina/sangue , Resistência à Insulina , Transtornos do Metabolismo dos Lipídeos/metabolismo , Lipídeos/sangue , Masculino , Nicotinamida Fosforribosiltransferase/metabolismo , Obesidade/sangue , Obesidade/metabolismo , Ratos , Ratos Mutantes , Triglicerídeos/sangue