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1.
Br J Clin Pharmacol ; 82(6): 1477-1485, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27434056

RESUMO

AIMS: Low blood concentrations of the naturally occurring amino acid L-homoarginine (L-hArg) are related to impaired cardiovascular outcome and mortality in humans and animals. L-hArg is a weak substrate of nitric oxide synthase and an inhibitor of arginases in vitro. The aim of our study was to obtain kinetic and dynamic data after oral L-hArg supplementation. METHODS: In a double-blind, randomized, placebo-controlled crossover study, 20 young volunteers received 125 mg L-hArg once daily for 4 weeks. Kinetic parameters (Cmax , Tmax and AUC0-24h ) were calculated after ingestion of single and multiple doses of oral supplementation as primary endpoint. Secondary endpoints that were evaluated were routine laboratory, L-arginine, asymmetric dimethylarginine (ADMA), pulse wave velocity (PWV), augmentation index (AIx), flow-mediated vasodilatation (FMD), corticospinal excitability, i.e. motor threshold (MT), and cortical excitability, i.e. intracortical inhibition (ICI) and facilitation (ICF). RESULTS: One hour after ingestion (Tmax ), L-hArg increased the baseline L-hArg plasma concentration (2.87 ± 0.91 µmol l-1 , mean ± SD) by 8.74 ± 4.46 [95% confidence intervals 6.65; 10.9] and 17.3 ± 4.97 [14.9; 19.6] µmol l-1 (Cmax ), after single and multiple doses, respectively. Once-only and 4 weeks of supplementation resulted in AUCs0-24h of 63.5 ± 28.8 [50.0; 76.9] and 225 ± 78.5 [188; 2624] µmol l-1 *h, for single and multiple doses, respectively. Routine laboratory parameters, L-arginine, ADMA, PWV, AIx, FMD, MT, ICI and ICF did not change by L-hArg supplementation compared to baseline. CONCLUSION: Once daily orally applied 125 mg L-hArg raises plasma L-hArg four- and sevenfold after single dose and 4 weeks of supplementation, respectively, and is safe and well tolerated in young volunteers.


Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Endotélio Vascular/efeitos dos fármacos , Homoarginina/sangue , Administração Oral , Adulto , Área Sob a Curva , Estudos Cross-Over , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Voluntários Saudáveis , Homoarginina/administração & dosagem , Homoarginina/efeitos adversos , Humanos , Masculino , Adulto Jovem
2.
J Sci Food Agric ; 95(7): 1414-20, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-24954190

RESUMO

BACKGROUND: Lathyrus species as legumes represent an alternative protein source for human and animal nutrition. Heavy consumption of these species can lead to lathyrism, caused by the non-protein amino acid ß-N-oxalyl-l-α,ß-diaminopropionic acid (ß-ODAP). Currently, there is no well-defined level below which ß-ODAP is considered non-toxic. In this work, the ß-ODAP content was determined in L. sativus and L. cicera samples to assess their potential toxicity. Homoarginine is another non-protein amino acid found in Lathyrus spp. with interesting implications for human and animal nutrition. RESULTS: The level of ß-ODAP found in these two species ranged from 0.79 to 5.05 mg g(-1). The homoarginine content of the samples ranged from 7.49 to 12.44 mg g(-1). CONCLUSION: This paper describes an accurate, fast and sensitive method of simultaneous detection and quantification of ß-ODAP and homoarginine by capillary zone electrophoresis in L. cicera and L. sativus seeds. Moreover, several methods of extraction were compared to determine the highest performance.


Assuntos
Homoarginina/análise , Lathyrus/química , Sementes/química , beta-Alanina/análogos & derivados , Animais , Dieta , Proteínas Alimentares , Eletroforese Capilar/métodos , Homoarginina/efeitos adversos , Humanos , Latirismo/etiologia , Lathyrus/efeitos adversos , beta-Alanina/efeitos adversos , beta-Alanina/análise
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