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Doctoral Thesis
DOI
10.11606/T.9.2017.tde-02082017-160501
Document
Author
Full name
Edimar Cristiano Pereira
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2006
Supervisor
Committee
Abdalla, Dulcineia Saes Parra (President)
Gomes, Ligia Ferreira
Junqueira, Virginia Berlanga Campos
Maranhao, Raul Cavalcante
Salgado Filho, Wilson
Title in Portuguese
Avaliação dos metabólitos do óxido nítrico, inibidores endógenos do óxido nítrico sintase e homocisteína na intolerância à glicose e no diabetes
Keywords in Portuguese
Bioquímica clínica
Diabetes Mellitus
Óxido nítrico
Abstract in Portuguese
A redução da biodisponibilidade óxido nítrico (NO) tem sido responsável por complicações vasculares em algumas doenças, incluindo Diabetes Mellitus tipo 2 (DMII). A disfunção endotelial (DE) pode ser ocasionada pela baixa biodisponibilidade do NO e estudos indicam que a hiperglicemia pode estar contribuindo para esse evento. Outro fato importante é que grande parte dos indivíduos que apresentam Intolerância à Glicose (IG) evolui para DMII. Portanto, o objetivo desse trabalho foi avaliar de que forma o estado hiperglicêmico poderia interferir sobre os metabólitos do NO (S-nitrosotióis, nitrato + nitrito e nitrotirosina), inibidores endógenos da NO sintase (ADMA e SDMA), homocisteína e a DE através da medida da atividade da n-acetil-β-glicosaminidase (NAG). Neste estudo participaram 140 voluntários: 12 controles (C), 32 IG e 96 DMII. A concentração de glicose foi superior nos grupos IG (109±10mg/dL) e DMII (165±66mg/dL) em relação ao grupo C (88±11mg/dL) (p<0.05). Somente o grupo DMII (8,5±1,9%; 4,57±2,78mg/dL) apresentou níveis elevados de hemoglobina glicada e frutosamina em relação ao grupo C (6,0±0,9%; 2,31±0,27mg/dL). Entretanto, os metabólitos do NO (nitrato+nitrito, S-nitrosotióis e nitrotirosina) apresentaram concentrações elevadas nos grupos IG (35,1±12,9µM; 137±45nM; 352±104nM) e DMII (39,2±18,0µM; 143±73nM 472±231nM) em relação ao grupo C (26,6±6,2µM; 78±46nM; 260±74nM). A função endotelial também esteve alterada nos grupos IG (28,0±7,3U/L) e DMII (29,4±8,7U/L) em relação ao grupo C (21,7±3,9U/L), como indicado pela atividade da NAG. O mesmo comportamento foi observado com os inibidores endógenos de NO (ADMA e SDMA). A concentração de homocisteína plasmática não apresentou diferença significativa entre os grupos. Os dados demonstraram que os indivíduos IG apresentaram alterações bioquímicas, relacionadas ao estresse oxidativo e à disfunção endotelial, semelhantes aos pacientes com DMII, as quais poderiam contribuir para o desenvolvimento de doenças cardiovasculares.
Title in English
Evaluation of nitric oxide metabolites, endogenous inhibitors of nitric oxide synthase and homocysteine in the glucose intolerance and in the diabetes
Keywords in English
Clinical biochemistry
Diabetes Mellitus
Nitric oxide
Abstract in English
The nitric oxide (NO) has been responsible for vascular complications in some diseases, including Diabetes Mellitus type 2 (DMII). Endothelial dysfunction (ED) may be caused by NO low bioavailability and studies indicate that the hyperglycemia may be contributing to this event. Other important fact is that a large number of individuals who present Glucose Intolerance (GI) develop DMII. Therefore, the objective of this study was to evaluate the way the hyperglycemic state could interfere upon the NO metabolites (S-nitrosotiois, nitrate + nitrite and nitrotirosine), endogen inhibitors of NO synthase (ADMA, and SDMA) and the DE using n-acetyl-β-glicosaminidase (NAG) activity measure. In this study, 140 volunteers participated: 12 as controls (C), 32 GI and 96 DMII. Glucose concentration was superior in GI group (109±10 mg/dL) and DMII group (165±66mg/dL) in relation to group C (88±11mg/dL) (p<0.05). Only DMII group (8,5±1.9%; 4,57±2,78mg/dL) showed high leveIs of glicade hemoglobin and frutosamine in relation to group C (6,0±0,9%; 2,31±0,27mg/dL). However, NO metabolites (nitrate + nitrite, S-nitrosotiois and nitrotirosine) showed high concentrations in groups GI (35,1±12,9µM; 137±45nM; 352±104nM) and DMII (39,2±18,OµM; 143±73nM; 472±231nM) in relation to group C (26,6±6,2µM; 78±46nM; 260±74nM). The endothelial function was aIso altered in groups GI (28,0±7,3U/L) and DMII (29,4±8,7U/L) in relation to group C (21,7±3,9U/L), as indicated by NAG activity. The same behavior was observed with endogen inhibitors of NO (ADMA and SDMA). Plasmatic homocystein concentration has not shown significant difference between the groups. Data has shown that the individuaIs IG presented biochemistry alterations, related to the oxidative stress and the endothelial dysfunction, similar to the patients with DMII, which could contribute to the development of cardiovascular diseases.
 
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Publishing Date
2017-08-02
 
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