53 research outputs found
Early loss of cardiac function in acute myocardial infarction is associated with redox imbalance
BACKGROUND: The loss of viable myocardium subsequent to myocardial infarction (MI) impairs cardiac function, and oxidative stress is considered to be critical in this process. OBJECTIVES: To assess cardiac function and correlate it with oxidative stress and antioxidant levels in cardiac tissue at 48 h post-MI. METHODS: Adult male Wistar rats (n=6 per group) with a mean (± SD) weight of 229±24 g were randomly assigned to either an infarcted group or a control group. MI was induced by occlusion of the left coronary artery. Cardiac function was evaluated by measuring left ventricular (LV) ejection fraction, LV fractional shortening, cardiac output, myocardial performance index and the peak early diastolic velocity/peak atrial velocity ratio using echocardiography. The myocardial oxidative stress profile was assessed by measuring the reduced glutathione/oxidized glutathione ratio, H2O2 levels, peroxiredoxin-6 protein levels and activity levels of superoxide dismutase, catalase and glutathione peroxidase. Lipid peroxidation was quantified using chemiluminescence, and protein oxidation was determined by measuring protein carbonyl levels. RESULTS: LV ejection fraction and LV fractional shortening were lower in the infarcted group compared with the sham group, whereas the peak early diastolic velocity/peak atrial velocity ratio and myocardial performance index were significantly increased, indicating systolic dysfunction. Lipid peroxidation, protein carbonyls and superoxide dismutase and catalase activity levels did not differ between the groups. Peroxyredoxin-6 levels were increased in the infarcted group, while H2O2 levels were reduced. The reduced glutathione/oxidized glutathione ratio and the glutathione peroxidase activity were reduced in the infarcted group compared with control. DISCUSSION AND CONCLUSION: These data suggest that MI-induced cardiac dysfunction and impaired redox balance may be associated with the activation of counter-regulatory responses to maintain reduced H2O2 concentrations and, thereby, prevent further oxidative damage at this early time point.Fil: Vicente Tavares, Angela MarĂa. Universidade Federal do Rio Grande do Sul. Instituto de CiĂȘncias BĂĄsicas da Saude; BrasilFil: da Rosa Araujo, Alex Sande. Universidade Federal do Rio Grande do Sul; BrasilFil: Llesuy, Susana Francisca. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Oficina de CoordinaciĂłn Administrativa Houssay. Instituto de BioquĂmica y Medicina Molecular. Universidad de Buenos Aires. Facultad Medicina. Instituto de BioquĂmica y Medicina Molecular; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y BioquĂmica. Departamento de QuĂmica AnalĂtica y FisicoquĂmica. CĂĄtedra de QuĂmica General e InorgĂĄnica; ArgentinaFil: Khaper, Neelam. Universidade Federal do Rio Grande do Sul. Instituto de CiĂȘncias BĂĄsicas da Saude; BrasilFil: Rohde, Luis Eduardo. Universidade Federal do Rio Grande do Sul. Instituto de CiĂȘncias BĂĄsicas da Saude; BrasilFil: Clausell, Nadine. Universidade Federal do Rio Grande do Sul. Instituto de CiĂȘncias BĂĄsicas da Saude; BrasilFil: Bello Klein, Adriane. Universidade Federal do Rio Grande do Sul; Brasi
Bucindolol modulates cardiac remodeling by attenuating oxidative stress in H9c2 cardiac cells exposed to norepinephrine
The increased circulation of norepinephrine, found in the diseased heart as a result of sympathetic nervous system overactivation, is responsible for its cardiotoxic effects including pathological hypertrophy, cell death, and oxidative stress. Bucindolol is a third generation adrenergic blocker, which acts on the ÎČ1 and ÎČ2 receptors, and has additional α1 antagonist activity. Thus, the aim of this study was to investigate the action of bucindolol on oxidative stress, hypertrophy, cell survival, and cell death signaling pathways in H9c2 cardiac cells exposed to norepinephrine. H9c2 cells were incubated with 10 ÎŒM norepinephrine for 24 h in the presence or absence of bucindolol (10 ÎŒM) treatment for 8 h. Western blot was used to determine the expression of proteins for hypertrophy/survival and death signaling pathways. Flow cytometry was used to assess cell death via caspase-3/7 activity and propidium iodide and reactive oxygen species via measuring the fluorescence of CM-H2DCFDA. Norepinephrine exposure resulted in an increase in oxidative stress as well as cell death. This was accompanied by an increased protein expression of LC3B-II/I. The protein kinase B/mammalian target of the rapamycin (Akt/mTOR) pathway which is involved in cardiac remodeling process was activated in response to norepinephrine and was mitigated by bucindolol. In conclusion, bucindolol was able to modulate cardiac remodeling which is mediated by oxidative stress
Chronic glucocorticoid exposure causes brown adipose tissue whitening, alters wholeâbody glucose metabolism and increases tissue uncoupling proteinâ1
Abstract Adipose tissue (AT) has been found to exist in two predominant forms, white and brown. White adipose tissue (WAT) is the body's conventional storage organ, and brown adipose tissue (BAT) is responsible for nonâshivering thermogenesis which allows mammals to produce heat and regulate body temperature. Studies examining BAT and its role in wholeâbody metabolism have found that active BAT utilizes glucose and circulating fatty acids and is associated with improved metabolic outcomes. While the beiging of WAT is a growing area of interest, the possibility of the BAT depot to âwhitenâ and store more triglycerides also has metabolic and health implications. Currently, there are limited studies that examine the effects of chronic stress and its ability to induce a whiteâlike phenotype in the BAT depot. This research examined how chronic exposure to the murine stress hormone, corticosterone, for 4 weeks can affect the whitening process of BAT in C57BL/6 male mice. Separate treatments with mirabegron, a known ÎČ3âadrenergic receptor agonist, were used to directly compare the effects of corticosterone with a beiging phenotype. Corticosteroneâtreated mice had significantly higher body weight (p â€Â 0.05) and BAT mass (p â€Â 0.05), increased adipocyte area (p â€Â 0.05), were insulin resistant (p â€Â 0.05), and significantly elevated expressions of uncoupling protein 1 (UCPâ1) in BAT (p â€Â 0.05) while mitochondrial content remained unchanged. This whitened phenotype has not been previously associated with increased uncoupling proteins under chronic stress and may represent a compensatory mechanism being initiated under these conditions. These findings have implications for the study of BAT in response to chronic glucocorticoid exposure potentially leading to BAT dysfunction and negative impacts on wholeâbody glucose metabolism
Sensitive Electrochemical Detection of Nitric Oxide Release from Cardiac and Cancer Cells via a Hierarchical Nanoporous Gold Microelectrode
The
importance of nitric oxide (NO) in many biological processes
has garnered increasing research interest in the design and development
of efficient technologies for the sensitive detection of NO. Here
we report on a novel gold microelectrode with a unique three-dimensional
(3D) hierarchical nanoporous structure for the electrochemical sensing
of NO, which was fabricated via a facile electrochemical alloying/dealloying
method. Following the treatment, the electrochemically active surface
area (ECSA) of the gold microelectrode was significantly increased
by 22.9 times. The hierarchical nanoporous gold (HNG) microelectrode
exhibited excellent performance for the detection of NO with high
stability. On the basis of differential pulse voltammetry (DPV) and
amperometric techniques, the obtained sensitivities were 21.8 and
14.4 ÎŒA ÎŒM<sup>â1</sup> cm<sup>â2</sup>,
with detection limits of 18.1 ± 1.22 and 1.38 ± 0.139 nM,
respectively. The optimized HNG microelectrode was further utilized
to monitor the release of NO from different cells, realizing a significant
differential amount of NO generated from the normal and stressed rat
cardiac cells as well as from the untreated and treated breast cancer
cells. The HNG microelectrode developed in the present study may provide
an effective platform in monitoring NO in biological processes and
would have a great potential in the medical diagnostics
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