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Life Sci ; 250: 117585, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32243928

RESUMO

AIMS: Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) have been associated with risk factors for metabolic syndrome (MetS). Our objective was to evaluate the effect of nicotinamide (NAM) on the activities, expression and protein content of cholinesterases in a MetS model. MAIN METHODS: MetS was induced in male rats administrating 40% fructose to the drinking water for 16 weeks. Additionally, from 5th week onward, the carbohydrate solution was replaced by NAM, at several concentrations for 5 h each morning for the next 12 weeks. In the 15th week, the glucose tolerance test was conducted, and blood pressure was measured. After the treatment period had concluded, the biochemical profile; oxidant stress; proinflammatory markers; and the activity, quantity and expression of cholinesterases were evaluated, and molecular docking analysis was performed. KEY FINDINGS: The MetS group showed anthropometric, hemodynamic and biochemical alterations and increased cholinesterase activity, inflammation and stress markers. In the liver, cholinesterase activity and mRNA, free fatty acid, tumor necrosis factor-alpha (TNF-α), and thiobarbituric acid-reactive substance (TBARS) levels were increased, while reduced glutathione (GSH) levels were decreased. NAM partially or totally decreased risk factors for MetS, markers of stress and inflammation, and the activity (serum and liver) and expression (liver) of cholinesterases. Molecular docking analysis showed that NAM has a greater affinity for cholinesterases than acetylcholine (ACh), suggesting NAM as an inhibitor of cholinesterases. SIGNIFICANCE: Supplementation with 40% fructose induced MetS, which increased the activity and expression of cholinesterases, oxidative stress and the inflammation. NAM attenuated these MetS-induced alterations and changes in cholinesterases.


Assuntos
Inflamação/metabolismo , Síndrome Metabólica/tratamento farmacológico , Niacinamida/uso terapêutico , Estresse Oxidativo , Receptores Colinérgicos/metabolismo , Acetilcolinesterase/metabolismo , Animais , Antropometria , Anti-Inflamatórios/uso terapêutico , Arildialquilfosfatase/metabolismo , Butirilcolinesterase/metabolismo , Colinesterases/metabolismo , Frutose , Regulação da Expressão Gênica , Teste de Tolerância a Glucose , Hemodinâmica , Humanos , Peroxidação de Lipídeos , Fígado/enzimologia , Masculino , Síndrome Metabólica/induzido quimicamente , Simulação de Acoplamento Molecular , Ratos , Ratos Sprague-Dawley
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