Diabetes mellitus activates fetal gene program and intensifies cardiac remodeling and oxidative stress in aged spontaneously hypertensive rats

Rosa, Carlos J. P.; Xavier, N. P.; Campos, Dijon Henrique Salomé de; Fernandes, Ana Angélica Henrique; Cezar, M. D. M.; Martinez, Paula Felippe; Cicogna, Antônio Carlos; Gimenes, Camila; Gimenes, Rodrigo; Okoshi, Marina Politi; Okoshi, Katashi

doi:10.1186/1475-2840-12-152

Cited by 45 publications

(56 citation statements)

References 56 publications

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“…Diabetes is diagnosed by the presence of hyperglycemia together with biochemical alterations such as increase in lipid peroxidation and oxidative stress (4). Hyperglycemia-induced oxidative stress is an important factor involved in diabetic-cardiac complications (34). Excessive levels of ROS or reduction of the antioxidant defenses, such as SODs, CAT, or GPx have been repeatedly described for type 2 DM (44).…”

Section: Discussionmentioning

confidence: 99%

Protective effect of crocin and voluntary exercise against oxidative stress in the heart of high-fat diet-induced type 2 diabetic rats

et al. 2016

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Background: Oxidative stress plays a critical role in the pathogenesis and progression of type 2 diabetes and diabeticassociated cardiovascular complications. This study investigated the impact of crocin combined with voluntary exercise on heart oxidative stress indicator in high-fat diet-induced type 2 diabetic rats. Materials and methods: Rats were divided into four groups: diabetes, diabetic-crocin, diabetic-voluntary exercise, diabetic-crocin-voluntary exercise. Type 2 diabetes was induced by high-fat diet (4 weeks) and injection of streptozotocin (intraperitoneally, 35 mg/kg). Animals received crocin orally (50 mg/kg); voluntary exercise was performed alone or combined with crocin treatment for 8 weeks. Finally, malondialdehyde (MDA), activity of antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were measured spectrophotometrically. Results: Treatment of diabetic rats with crocin and exercise significantly decreased the levels of MDA (p < 0.001) and increased the activity of SOD, GPx, and CAT compared with the untreated diabetic group. In addition, combination of exercise and crocin amplified their effect on antioxidant levels in the heart tissue of type 2 diabetic rats. Conclusion: We suggest that a combination of crocin with voluntary exercise treatment may cause more beneficial effects in antioxidant defense system of heart tissues than the use of crocin or voluntary exercise alone.

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Section: Discussionmentioning

confidence: 99%

Protective effect of crocin and voluntary exercise against oxidative stress in the heart of high-fat diet-induced type 2 diabetic rats

et al. 2016

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“…Echocardiography was performed by the same blinded examiner using a Philips HDI 5000 apparatus with a 7-12 MHz multifrequency transducer. All parameters were obtained from parasternal long and short axis and apical four chambers [14,15,16,17]. Structural variables analyzed by Doppler-echocardiography were: left atrial diameter, left ventricular (LV) diastolic posterior wall thickness, and LV diastolic and systolic diameters.…”

Section: Methodsmentioning

confidence: 99%

Acute Doxorubicin-Induced Cardiotoxicity is Associated with Matrix Metalloproteinase-2 Alterations in Rats

Polegato

Minicucci

Azevedo

et al. 2015

Cell Physiol Biochem

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Background: Doxorubicin can cause cardiotoxicity. Matrix metalloproteinases (MMP) are responsible for degrading extracellular matrix components which play a role in ventricular dilation. Increased MMP activity occurs after chronic doxorubicin treatment. In this study we evaluated in vivo and in vitro cardiac function in rats with acute doxorubicin treatment, and examined myocardial MMP and inflammatory activation, and gene expression of proteins involved in myocyte calcium transients. Methods: Wistar rats were injected with doxorubicin (Doxo, 20 mg/kg) or saline (Control). Echocardiogram was performed 48 h after treatment. Myocardial function was assessed in vitro in Langendorff preparation. Results: In left ventricle, doxorubicin impaired fractional shortening (Control 0.59±0.07; Doxo 0.51±0.05; p<0.001), and increased isovolumetric relaxation time (Control 20.3±4.3; Doxo 24.7±4.2 ms; p=0.007) and myocardial passive stiffness. MMP-2 activity, evaluated by zymography, was increased in Doxo (Control 141338 ± 8924; Doxo 188874 ± 7652 arbitrary units; p<0.001). There were no changes in TNF-α, INF-γ, IL-10, and ICAM-1 myocardial levels. Expression of phospholamban, Serca-2a, and ryanodine receptor did not differ between groups. Conclusion: Acute doxorubicin administration induces in vivo left ventricular dysfunction and in vitro increased myocardial passive stiffness in rats. Cardiac dysfunction is related to myocardial MMP-2 activation. Increased inflammatory stimulation or changed expression of the proteins involved in intracellular calcium transients is not involved in acute cardiac dysfunction.

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“…The following parameters were measured from isometric contraction: peak of developed tension (DT, g/mm2), resting tension (RT, g/mm2), and maximum rate of tension development (+dT/dt, g/mm 2 /s). To evaluate myocardial contractile reserve, papillary muscle mechanical performance was evaluated at basal condition and after the following positive inotropic stimulation: post-rest contractions (10, 30, and 60 s), extracellular Ca 2+ concentration increase (external calcium concentrations of 0.625, 1.25, and 2.5 mM), and β-adrenergic agonist isoproterenol (10 -8 , 10 -7 , and 10 -6 M) addition to the nutrient solution [41]. Papillary muscle cross-sectional area was calculated from muscle weight and length by assuming cylindrical uniformity and a specific gravity of 1.0.…”

Section: Methodsmentioning

confidence: 99%

Long-Term Low Intensity Physical Exercise Attenuates Heart Failure Development in Aging Spontaneously Hypertensive Rats

Pagan

Damatto

Cezar

et al. 2015

Cell Physiol Biochem

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Background: Physical exercise is a strategy to control hypertension and attenuate pressure overload-induced cardiac remodeling. The influence of exercise on cardiac remodeling during uncontrolled hypertension is not established. We evaluated the effects of a long-term low intensity aerobic exercise protocol on heart failure (HF) development and cardiac remodeling in aging spontaneously hypertensive rats (SHR). Methods: Sixteen month old SHR (n=50) and normotensive Wistar-Kyoto (WKY, n=35) rats were divided into sedentary (SED) and exercised (EX) groups. Rats exercised in treadmill at 12 m/min, 30 min/day, 5 days/week, for four months. The frequency of HF features was evaluated at euthanasia. Statistical analyses: ANOVA and Tukey or Mann-Whitney, and Goodman test. Results: Despite slightly higher systolic blood pressure, SHR-EX had better functional capacity and lower HF frequency than SHR-SED. Echocardiography and tissue Doppler imaging showed no differences between SHR groups. In SHR-EX, however, left ventricular (LV) systolic diameter, larger in SHR-SED than WKY-SED, and endocardial fractional shortening, lower in SHR-SED than WKY-SED, had values between those in WKY-EX and SHR-SED not differing from either group. Myocardial function, assessed in LV papillary muscles, showed improvement in SHR-EX over SHR-SED and WKY-EX. LV myocardial collagen fraction and type I and III collagen gene expression were increased in SHR groups. Myocardial hydroxyproline concentration was lower in SHR-EX than SHR-SED. Lysyl oxidase gene expression was higher in SHR-SED than WKY-SED. Conclusion: Exercise improves functional capacity and reduces decompensated HF in aging SHR independent of elevated arterial pressure. Improvement in functional status is combined with attenuation of LV and myocardial dysfunction and fibrosis.

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Diabetes mellitus activates fetal gene program and intensifies cardiac remodeling and oxidative stress in aged spontaneously hypertensive rats

Cited by 45 publications

References 56 publications

Protective effect of crocin and voluntary exercise against oxidative stress in the heart of high-fat diet-induced type 2 diabetic rats

Protective effect of crocin and voluntary exercise against oxidative stress in the heart of high-fat diet-induced type 2 diabetic rats

Acute Doxorubicin-Induced Cardiotoxicity is Associated with Matrix Metalloproteinase-2 Alterations in Rats

Long-Term Low Intensity Physical Exercise Attenuates Heart Failure Development in Aging Spontaneously Hypertensive Rats

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