Cardiac Oxidative Stress Is Elevated at the Onset of Dilated Cardiomyopathy in Streptozotocin-Diabetic Rats

Crespo, Marı́a J.; Zalacain, Joaquin; Dunbar, Donald C.; Cruz, Nildris; Arocho, Lucy

doi:10.1177/1074248407307854

Cited by 38 publications

(32 citation statements)

References 34 publications

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“…Results from previous studies indicated that the cardiac function index including ejection fraction and stroke volume was depressed at 4 weeks following STZinduced diabetes (Crespo et al 2008(Crespo et al , 2011. Consistent with our findings, echocardiography showed a reduction of %FS and %LVEF in diabetic rats in this study.…”

Section: Discussionsupporting

confidence: 81%

Protocatechuic acid exerts a cardioprotective effect in type 1 diabetic rats

Semaming¹,

Kumfu²,

Pannangpetch³

et al. 2014

Journal of Endocrinology

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Oxidative stress has been shown to play an important role in the pathogenesis of diabetesinduced cardiac dysfunction. Protocatechuic acid (PCA) is a phenolic compound, a main metabolite of anthocyanin, which has been reported to display various pharmacological properties. We proposed the hypothesis that PCA exerts cardioprotection in type 1 diabetic (T1DM) rats. T1DM was induced in male Sprague-Dawley rats by a single i.p. injection of 50 mg/kg streptozotocin (STZ) and groups of these animals received the following treatments for 12 weeks: i) oral administration of vehicle, ii) oral administration of PCA at a dose of 50 mg/kg per day, iii) oral administration of PCA at a dose of 100 mg/kg per day, iv) s.c. injection of insulin at a dose of 4 U/kg per day, and v) a combination of PCA, 100 mg/kg per day and insulin, 4 U/kg per day. Metabolic parameters, results from echocardiography, and heart rate variability were monitored every 4 weeks, and the HbA1c, cardiac malondialdehyde (MDA), cardiac mitochondrial function, and cardiac BAX/BCL2 expression were evaluated at the end of treatment. PCA, insulin, and combined drug treatments significantly improved metabolic parameters and cardiac function as shown by increased percentage fractional shortening and percentage left ventricular ejection fraction and decreased low-frequency:high-frequency ratio in T1DM rats. Moreover, all treatments significantly decreased plasma HbA1c and cardiac MDA levels, improved cardiac mitochondrial function, and increased BCL2 expression. Our results demonstrated for the first time, to our knowledge, the efficacy of PCA in improving cardiac function and cardiac autonomic balance, preventing cardiac mitochondrial dysfunction, and increasing anti-apoptotic protein in STZ-induced T1DM rats. Thus, PCA possesses a potential cardioprotective effect and could restore cardiac function when combined with insulin treatment. These findings indicated that supplementation with PCA might be helpful for the prevention and alleviation of cardiovascular complications in T1DM.

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Section: Discussionsupporting

confidence: 81%

Protocatechuic acid exerts a cardioprotective effect in type 1 diabetic rats

Semaming¹,

Kumfu²,

Pannangpetch³

et al. 2014

Journal of Endocrinology

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“…27- 31 Others have shown that oxidative stress is increased in both type I and type II DM. 32, 33 Hyperglycemia induces oxidative stress through several pathways, 10-13, 34 including enhanced aldose reductase activity, 10 increased advanced glycation end-products, 11 altered protein kinase C activity 12 and mitochondrial overproduction of superoxide. 13 Matsushima et al found that glutathione peroxidase overexpression improved LV diastolic function, accompanied by the attenuation of myocyte hypertrophy, interstitial fibrosis and apoptosis, in mice with STZ-induced DM.…”

Section: Effects Of Fluvastatin On Cardiac Oxidative Stressmentioning

confidence: 99%

Fluvastatin Attenuates Diabetes-Induced Cardiac Sympathetic Neuropathy in Association With a Decrease in Oxidative Stress

Matsuki

Nozawa

Igarashi

et al. 2010

Circ J

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Background: Increased oxidative stress might contribute to diabetic (DM) neuropathy, so the effects of longterm treatment with fluvastatin (FL) on myocardial oxidative stress and cardiac sympathetic neural function were investigated in diabetic rats.Methods and Results: FL (10 mg · kg -1 · day -1 , DM-FL) or vehicle (DM-VE) was orally administered for 2 weeks to streptozotocin-induced DM rats. Cardiac oxidative stress was determined by myocardial 8-iso-prostaglandin F2α (PGF2α) and NADPH oxidase subunit p22 phox mRNA expression. Sympathetic neural function was quantified by autoradiography using 131 I- and 125 I-metaiodobenzylguanidine (MIBG). FL did not affect plasma glucose levels but remarkably decreased PGF2α levels compared with DM-VE rats (13.8±9.2 vs 175.0±93.9 ng/g tissue), although PGF2α levels were below the detection limit in non-DM rats. FL significantly reduced myocardial p22 phox mRNA expression. Cardiac 131 I-MIBG uptake was lower in DM-VE rats than in non-DM rats, but the decrease was attenuated in DM-FL rats (1.31±0.08, 1.88±0.22, and 1.58±0.18 %kg dose/g, respectively, P<0.01). Cardiac MIBG clearance was not affected by the induction of DM or by FL, indicating that the reduced MIBG uptake in DM rats might result from impaired neural function. Diabetes-Induced Cardiac NeuropathyExperimental Animals DM was induced in male Wistar rats weighing 250-300 g by an intraperitoneal injection of 65 mg/kg of streptozotocin (STZ, n=40). Non-DM control rats (n=14) were not injected with STZ. The rats with glucose levels >250 mg/dl at 1 week after STZ injection were considered diabetic (n=28) and used in the experiments. Two weeks later, fluvastatin (10 mg · kg -1 · day -1 , n=14) or vehicle (DM controls: 0.1% carboxymethyl cellulose, n=14) was orally administered by gavage for 2 weeks. Standard rat chow and tap water were provided ad libitum throughout the study.Systolic blood pressure and heart rate were measured using an indirect tail-cuff method (BP-98A, Softron) and lipid peroxides (LPO) in plasma were determined using a hemoglobin-methylene blue method that selectively detects the absolute quantity of LOOH. Cardiac oxidative stress was then assessed as the levels of 8-isoprostaglandin F2α (PGF2α) and nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase subunit p22 phox mRNA expression, and cardiac sympathetic neural function was assessed using 131 I-and 125 Ilabeled MIBG.Radioactive MIBG Tracers FUJIFILM RI Pharma Co Ltd (Tokyo, Japan) prepared and supplied 131 I-and 125 I-labeled MIBG at a radiochemical purity >98%, and specific activity of 30-70 GBq/mmol. Cardiac MIBG AccumulationDual-tracer autoradiography proceeded as described. 22,23 Briefly, 0.37 MBq of 125 I-MIBG was injected via the external jugular vein under pentobarbital sodium anesthesia (30 mg/kg, ip). Two hours later, 1.85 MBq of 131 I-MIBG was intravenously injected and 30 min thereafter, the heart was removed and washed in cold saline. Specimens were frozen in isopentane, cooled in dry ice, embedded in methyl cellulose and cut in...

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“…Previous results from our laboratory revealed that the cardiac output index, ejection fraction and stroke volume decrease 4 weeks following diabetes induction [20,22]. The etiology of these alterations is unknown, but it does accompany abnormalities of cardiac endothelial nitric oxide synthase (eNOS) and inducible NOS [20].…”

Section: Discussionmentioning

confidence: 99%

“…The etiology of these alterations is unknown, but it does accompany abnormalities of cardiac endothelial nitric oxide synthase (eNOS) and inducible NOS [20]. In addition, diabetic rats are hypercholesterolemic at this stage [23].…”

Section: Discussionmentioning

confidence: 99%

“…The animals were first tested 24 h after receiving a single statin dose and a second time after continued daily administration for 1 week. The echocardiographic method, which has been described previously [20,21], employed a digital portable ultrasound system (Model 180P, Sonosite Inc., Wash., USA) equipped with a pulsed-wave Doppler sonograph and a transducer having a wide bandwidth of 7.5-9.0 MHz. The animals were anesthetized by injecting sodium pentobarbital (30 mg/kg body weight, BW, i.p.…”

Section: Methodsmentioning

confidence: 99%

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Daily Administration of Atorvastatin and Simvastatin for One Week Improves Cardiac Function in Type 1 Diabetic Rats

Crespo

Cruz²,

Quidgley³

et al. 2014

Pharmacology

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Short-term administration of statins during the perioperative period has been suggested to improve cardiovascular (CV) outcomes in patients undergoing cardiac and vascular surgery. The effectiveness of this therapy, the optimal administration time and the statin best suited to improve cardiac performance under hyperglycemic conditions, however, are unknown. In this study, we compared the effects of 10 mg/kg/day simvastatin (SV), pravastatin (PV) and atorvastatin (AV), on the CV status of fully anesthetized streptozotocin-induced diabetic rats 4 weeks following diabetes induction. At this stage, cardiac function is compromised. The rats were anesthetized to mimic presurgical conditions. Cardiac status was evaluated twice by echocardiography, first 24 h after statin administration, and then after daily statin administration for 1 week. After 24 h of statin administration, CV parameters were not improved. Continued daily administration of SV and AV over a 1-week period, by contrast, significantly improved ejection fraction from 52.20 ± 2.33% before treatment to 64.89 ± 1.12% with AV and to 69.71 ± 2.30% with SV (n = 9, p < 0.05). The cardiac output index was also significantly improved from 51.13 ± 6.86 ml/min × 100 g body weight (BW) before treatment to 98.74 ± 13.78 ml/min × 100 g BW with AV and to 84.94 ± 8.64 ml/min × 100 g BW with SV. Only AV increased stroke volume from 0.50 ± 0.08 to 0.83 ± 0.13 ml (n = 9, p < 0.05). Unlike the other statins tested, PV provided no beneficial effects, regardless of the regimen of administration. Our results indicate that daily administration of AV and SV for 1 week enhances cardiac performance in fully anesthetized diabetic rats. This study of short-term statin administration may have strong clinical implications for improving perioperative outcomes in diabetic patients.

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Cardiac Oxidative Stress Is Elevated at the Onset of Dilated Cardiomyopathy in Streptozotocin-Diabetic Rats

Cited by 38 publications

References 34 publications

Protocatechuic acid exerts a cardioprotective effect in type 1 diabetic rats

Protocatechuic acid exerts a cardioprotective effect in type 1 diabetic rats

Fluvastatin Attenuates Diabetes-Induced Cardiac Sympathetic Neuropathy in Association With a Decrease in Oxidative Stress

Daily Administration of Atorvastatin and Simvastatin for One Week Improves Cardiac Function in Type 1 Diabetic Rats

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