Role of redox imbalance in the pathogenesis of the Metabolic syndrome: cardiometabolic repercussions and in the arterial function

Autor: Fonseca, Lucas José Sá da
Přispěvatelé: Rabelo, Luíza Antas, Rossoni, Luciana Venturini, Rodrigues, Célio Fernando de Souza, Ribeiro, Êurica Adélia Nogueira
Jazyk: portugalština
Rok vydání: 2012
Předmět:
Zdroj: Repositório Institucional da Universidade Federal de Alagoas (UFAL)
Universidade Federal de Alagoas (UFAL)
instacron:UFAL
Popis: Introduction: The Metabolic Syndrome (MetS) is caracterized by a complex cluster of cardiometabolic disorders capable of augmenting the cardiovascular risk of its carriers. Although existing descriptions related to the association among such syndrome, oxidative stress and arterial function, many of the mechanisms involved in its pathophysiology still remain to be elucidated. Before these observations, the present study aimed to verify the redox balance profile in the pathogenesis of the MetS in human carriers, when compared to control ones, and its cardiometabolic and arterial function outcomes; Methods: For this observational study, 24 patients presenting with MetS were selected from the Federal University of Alagoas Teaching Hospital and 18 apparently healthy individuals from a private clinic, all of them age, sex, tobacco use and socioeconomic status-matched. The diagnosis for the cases was established according to the Harmonized version of the MetS (2009). During the clinical assessment, blood pressure levels and heart rate were obtained, followed by the anthropometric measurements: weight, height, waist circumference (WC), body mass index (BMI), waist-to-hip ratio (WHR) and neck circumference (NC). After a 12-hour fasting period, venous blood samples were collected for general biochemical dosages [glycemic and lipid profile, AST, ALT, high-sensitive C-reactive protein (hs CRP), urea, creatinine and uric acid], as well as for the oxidative stress analyses (serum lipid peroxidation, SOD, catalase, arginase, glutathione peroxidase and myeloperoxidase enzymatic activities, as well as serum nitrite and hydrogen peroxide – H2O2 – concentrations). Estimated glomerular filtration rate (eGFR) was calculated base on the MDRD formula. The non-invasive assessment of the arterial function was performed using radial applanation tonometry, being obtained the augmentation index (AI); Results: Patients with MetS presented greater obesity indices than the respective controls (BMI: controls 26.69 ± 3.27 vs MetS 32.09 ± 7.10 kg.m-2, p < 0.01; WC: controls 87.89 ± 7.65 vs MetS 103.3 ± 13.96 cm, p < 0.0001; WHR: controls 0.83 ± 0.06 vs MetS 0.90 ± 0.09, p < 0.01; NC: 34.92 ± 3.24 vs MetS 37.46 ± 5.99 cm, p < 0.05), besides higher blood pressure levels and major loss of glycemic and lipid control. The case group presented higher levels for the markers of liver damage and uric acid, as well as reduced eGFR. Serum lipid peroxidation (controls 4.40 ± 0.65 vs MetS 7.99 ± 4.19 [MDA] mM.[Protein] mg.mL-1, p < 0.0001), erythrocyte SOD activity (controls 83.14 ± 57.27 vs MetS 128.60 ± 55.88 UI.mg Hb-1, p < 0.01), serum myeloperoxidase activity (controls 2.36 ± 0.33 vs MetS 2.80 ± 0.53 UI.mL-1.Protein mg.mL-1; p < 0.01) and H2O2 (controls 221.30 ± 181.70 vs MetS 501.00 ± 283.80 nmol.L-1; p < 0.001) were shown to be increased in the MetS group, with no statistically significant differences for the other considered enzymes, nitrite concentrations and the arterial assessment (AI) between the considered groups. Correlation analyses were more expressive between lipid peroxidation and obesity indices/biochemical profile; Conclusion: In patients with MetS, the greater indices of obesity and blood pressure were accompanied by a considerable loss of biochemical regulation compared to controls, although the specific pharmacological therapy in the case group. The lack of difference for the marker of arterial stiffness may indicate the probable influence of the current drug therapy. Furthermore, patients with MetS exhibited evident systemic redox imbalance compared to controls, with the probable participation of the MPO-H2O2 pathway as a contributor in the lipoperoxidation observed in individuals with MetS. Finally, the observed correlations point to the important role of oxidative stress in the maintenance of metabolic disturbances related to the MetS. CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Introdução: A Síndrome Metabólica (SMet) caracteriza-se pela complexa associação de desordens cardiometabólicas capazes de aumentar o risco cardiovascular de indivíduos por ela acometidos. Apesar de descrições quanto à associação entre esta síndrome, o estresse oxidativo e a função arterial, muitos dos mecanismos envolvidos em sua fisiopatologia não são ainda completamente compreendidos. Diante disso, o presente estudo objetivou verificar o perfil do balanço redox na patogenia da SMet em humanos, comparando-os aos respectivos controles, e suas repercussões cardiometabólicas e na função arterial; Métodos: Para este estudo observacional, foram selecionados 24 pacientes com SMet atendidos no Hospital Escola da Universidade Federal de Alagoas e 18 indivíduos aparentemente saudáveis provenientes de uma clínica privada, pareados por idade, sexo, tabagismo e perfil socioeconômico. O diagnóstico do grupo de casos foi estabelecido segundo os critérios da versão Harmonizada da SMet (2009). Durante a avaliação clínica, foram obtidos os valores de pressão arterial e frequência cardíaca, seguindo-se as medidas antropométricas: peso, altura, circunferência abdominal (CA), índice de massa corporal (IMC), relação cintura-quadril (RCQ) e circunferência do pescoço (CP). Após jejum noturno de 12 horas, foram colhidas amostras de sangue venoso para dosagens bioquímicas gerais [perfil glicêmico, lipídico, AST, ALT, proteína C reativa ultrassensível (PCR US), ureia, creatinina e ácido úrico], bem como para as análises do estresse oxidativo (peroxidação lipídica plasmática, atividades das enzimas do balanço redox SOD, catalase, arginase, mieloperoxidase, além da dosagem plasmática de nitrito e peróxido de hidrogênio – H2O2). A taxa de filtração glomerular estimada (TFGe) foi calculada com base na fórmula MDRD. A avaliação não invasiva da função arterial foi acessada através de tonometria de aplanação da artéria radial esquerda, com a obtenção do índice de amplificação (AI); Resultados: Os pacientes do grupo SMet apresentaram maiores índices de obesidade que os respectivos controles (IMC: controles 26,69 ± 3,27 vs SMet 32,09 ± 7,10 kg.m-2, p
Databáze: OpenAIRE
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