RESUMO
Relationship between hyperfibrinogenemia (HF), oxidative stress, and atherogenesis was established. Effect of atorvastatin (Ator) was assessed. Wistar male (6 months) rats were studied: Ctr, control, without HF induction; Ctr-Ator, without HF treated with atorvastatin; AI, atherogenesis induced, and AI-Ator, atherogenesis induced and treated with atorvastatin. Atherogenesis was induced by daily adrenaline injection (0.1 mL/day/rat) for 90 days; treatment started 15 days after induction. Fibrinogen (mg/dL) and nitric oxide (NO) were measured in plasma (mM) and superoxide dismutase (SOD) (U/mL) in red cell lysate by spectrophotometry. Slices of aorta were analyzed by electron microscopy (EM). ANOVA and chi-square test were used; P < 0.05 was established. There were no significant differences between Ctr and Ctr-Atorv in fibrinogen, NO, and SOD values. Comparing Ctr with AI an increase of fibrinogen is observed (P < 0.001), but it decreased after administration of atorvastatin in AI-Ator (P < 0.001). NO diminished in AI relative to Ctr and increased in AI-Ator (P < 0.001). SOD showed an increase in AI and AI-Ator compared to Ctr (P < 0.001). EM revealed expansion of intermembrane space and disorganization of crests in AI. In AI-Ator mitochondrial areas and diameters were similar to control. Atorvastatin normalizes HF, stabilizes NO, increases SOD, and produces a partial regression of mitochondrial lesions.
RESUMO
Existen evidencias que asocian biomarcadores inflamatorios con síndrome metabólico (SM), insulinoresistencia y enfermedad aterogénica subclínica (ATS), pero no está clara su interrelación y como contribuirían al desarrollo de estas patologías multisindrómicas. El componente inflamatorio sería la vía final común reflejada por la disfunción endotelial y la inducción de estrés oxidativo. Se diseñó un modelo experimental de SM mediante la administración de fructuosa al 10% diluída en agua de bebida por 6 semanas y de ATS inducida por hiperfibrinogenemia (HF) en diferentes períodos experimentales. Se determinó en todos los grupos estudiados: glucemia, insulinemia, perfil lipídico, cálculo de HOMA (homeostasis model assessment) y se cuantificaron por espectrofotometría biomarcadores inflamatorios y de estrés oxidativo: fibrinógeno, oxido nítrico (NO), L-citrulina, adiponectina y superóxido dismutasa (SOD). Se analizó por microscopia óptica la anatomía patológica de aorta torácica e hígado. Se determinaron las probables alteraciones morfológicas mitocondriales en células musculares lisas aórticas por microscopia electrónica y para valorar funcionalidad se determinó la actividad enzimática de Citrato Sintasa y los complejos I, II, III y IV de la cadena respiratoria mitocondrial.
SUMMARY: There is evidence to associate inflammatory biomarkers with metabolic syndrome (MS), insulin resistance and atherogenic subclinical disease (ASD), but it is unclear their interrelationship and how would it contribute to the development and progression of these multisindromical pathologies. The inflammatory component would be the final common pathway reflected by endothelial dysfunction and induction of oxidative stress. An experimental model of MS was designed by administering diluted fructose to 10% in drinking water for6 weeks and ASD induced by hyperfibrinogenemia (HF) in different experimental periods. Glucose, insulin, lipid profile and HOMA calculation (homeostasis model assessment) was determined in all groups studied. Inflammatory and oxidative stress biomarkers: fibrinogen, nitric oxide (NO), L-citrulline, adiponectin and superoxide dismutase (SOD) were quantified by spectrophotometry. Thoracic aorta and liver histopathology were analyzed by optical microscopy. Probable mitochondrial morphological changes in aortic smooth muscle cells were determined by electron microscopy and functional alterations were measured by the enzymatic activity of citrate synthase and complex I, II, III and IV of the mitochondrial respiratory chain.
