DENISE DE CASTRO FERNANDES
Projetos de Pesquisa
Unidades Organizacionais
LIM/19 - Laboratório de Histocompatibilidade e Imunidade Celular, Hospital das Clínicas, Faculdade de Medicina
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article 36 Citação(ões) na Scopus Tobacco Smoke Induces Ventricular Remodeling Associated with an Increase in NADPH Oxidase Activity(2011) RAFACHO, Bruna P. M.; AZEVEDO, Paula S.; POLEGATO, Bertha F.; FERNANDES, Ana A. H.; BERTOLINE, Maria A.; FERNANDES, Denise C.; CHIUSO-MINICUCCI, Fernanda; ROSCANI, Meliza G.; SANTOS, Priscila P. dos; MATSUBARA, Luiz S.; MATSUBARA, Beatriz B.; LAURINDO, Francisco R. M.; PAIVA, Sergio A. R.; ZORNOFF, Leonardo A. M.; MINICUCCI, Marcos F.Background: Recent studies have assessed the direct effects of smoking on cardiac remodeling and function. However, the mechanisms of these alterations remain unknown. The aim of this study was to investigate de role of cardiac NADPH oxidase and antioxidant enzyme system on ventricular remodeling induced by tobacco smoke. Methods: Male Wistar rats that weighed 200-230 g were divided into a control group (C) and an experimental group that was exposed to tobacco smoke for a period of two months (ETS). After the two-month exposure period, morphological, biochemical and functional analyses were performed. Results: The myocyte cross-sectional area and left ventricle end-diastolic dimension was increased 16.2% and 33.7%, respectively, in the ETS group. The interstitial collagen volume fraction was also higher in ETS group compared to the controls. In addition to these morphological changes, the ejection fraction and fractional shortening were decreased in the ETS group. Importantly, these alterations were related to augmented heart oxidative stress, which was characterized by an increase in NADPH oxidase activity, increased levels of lipid hydroperoxide and depletion of antioxidant enzymes (e.g., catalase, superoxide dismutase and glutathione peroxidase). In addition, cardiac levels of IFN-gamma, TNF-alpha and IL-10 were not different between the groups. Conclusion: Cardiac alterations that are induced by smoking are associated with increased NADPH oxidase activity, suggesting that this pathway plays a role in the ventricular remodeling induced by exposure to tobacco smoke.- Modulation of MAPK and NF-kappa B Signaling Pathways by Antioxidant Therapy in Skeletal Muscle of Heart Failure Rats(2016) MARTINEZ, Paula F.; BONOMO, Camila; GUIZONI, Daniele M.; OLIVEIRA JUNIOR, Silvio A.; DAMATTO, Ricardo L.; CEZAR, Marcelo D. M.; LIMA, Aline R. R.; PAGAN, Luana U.; SEIVA, Fabio R.; BUENO, Renata T.; FERNANDES, Denise C.; LAURINDO, Francisco R.; ZORNOFF, Leonardo A. M.; OKOSHI, Katashi; OKOSHI, Marina P.Background/Aims: Although increased oxidative stress plays a role in heart failure (HF)-induced skeletal myopathy, signaling pathways involved in muscle changes and the role of antioxidant agents have been poorly addressed. We evaluated the effects of N-acetylcysteine (NAC) on intracellular signaling pathways potentially modulated by oxidative stress in soleus muscle from HF rats. Methods and Results: Four months after surgery, rats were assigned to Sham, myocardial infarction (MI)-C (without treatment), and MI-NAC (treated with N-acetylcysteine) groups. Two months later, echocardiogram showed left ventricular dysfunction in MI-C; NAC attenuated diastolic dysfunction. Oxidative stress was evaluated in serum and soleus muscle; malondialdehyde was higher in MI-C than Sham and did not differ between MI-C and MI-NAC. Oxidized glutathione concentration in soleus muscle was similar in Sham and MI-C, and lower in MI-NAC than MI-C (Sham 0.168 +/- 0.056; MI-C 0.223 +/- 0.073; MI-NAC 0.136 +/- 0.023 nmol/mg tissue; p = 0.014). Western blot showed increased p-JNK and decreased p38, ERK1/2, and p-ERK1/2 in infarcted rats. NAC restored ERK1/2. NF-kappa B p65 subunit was reduced; p-Ser276 in p65 and I kappa B was increased; and p-Ser536 unchanged in MI-C compared to Sham. NAC did not modify NF-kappa B p65 subunit, but decreased p-Ser276 and p-Ser536. Conclusion: N-acetylcysteine modulates MAPK and NF-kappa B signaling pathways in soleus muscle of HF rats. (C) 2016 The Author(s) Published by S. Karger AG, Basel
- Influence of N-Acetylcysteine on Oxidative Stress in Slow-Twitch Soleus Muscle of Heart Failure Rats(2015) MARTINEZ, Paula F.; BONOMO, Camila; GUIZONI, Daniele M.; OLIVEIRA JUNIOR, Silvio A.; DAMATTO, Ricardo L.; CEZAR, Marcelo D. M.; LIMA, Aline R. R.; PAGAN, Luana U.; SEIVA, Fabio R.; FERNANDES, Denise C.; LAURINDO, Francisco R. M.; NOVELLI, Ethel L. B.; MATSUBARA, Luiz S.; ZORNOFF, Leonardo A. M.; OKOSHI, Katashi; OKOSHI, Marina P.Background: Chronic heart failure is characterized by decreased exercise capacity with early exacerbation of fatigue and dyspnea. Intrinsic skeletal muscle abnormalities can play a role in exercise intolerance. Causal or contributing factors responsible for muscle alterations have not been completely defined. This study evaluated skeletal muscle oxidative stress and NADPH oxidase activity in rats with myocardial infarction (MI) induced heart failure. Methods and Results: Four months after MI, rats were assigned to Sham, MI-C (without treatment), and MI-NAC (treated with N-acetylcysteine) groups. Two months later, echocardiogram showed left ventricular dysfunction in MI-C; NAC attenuated diastolic dysfunction. In soleus muscle, glutathione peroxidase and superoxide dismutase activity was decreased in MI-C and unchanged by NAC. 3-nitrotyrosine was similar in MI-C and Sham, and lower in MI-NAC than MI-C. Total reactive oxygen species (ROS) production was assessed by HPLC analysis of dihydroethidium (DHE) oxidation fluorescent products. The 2-hydroxyethidium (EOH)/DHE ratio did not differ between Sham and MI-C and was higher in MI-NAC. The ethidium/DHE ratio was higher in MI-C than Sham and unchanged by NAC. NADPH oxidase activity was similar in Sham and MI-C and lower in MI-NAC. Gene expression of p47(phox) was lower in MI-C than Sham. NAC decreased NOX4 and p22(phox) expression. Conclusions: We corroborate the case that oxidative stress is increased in skeletal muscle of heart failure rats and show for the first time that oxidative stress is not related to increased NADPH oxidase activity.