PKCβ inhibition with ruboxistaurin reduces oxidative stress and attenuates left ventricular hypertrophy and dysfuntion in rats with streptozotocin-induced diabetes

2011 ◽  
Vol 122 (4) ◽  
pp. 161-173 ◽  
Author(s):  
Yanan Liu ◽  
Shaoqing Lei ◽  
Xia Gao ◽  
Xiaowen Mao ◽  
Tingting Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Body Weight ◽  
Nadph Oxidase ◽  
Myocardial Hypertrophy ◽  
Weight Ratio ◽  
Cardiovascular Complications ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Control Group ◽  
Cross Sectional

Oxidative stress plays critical roles in the development of diabetic cardiovascular complications, including myocardial hypertrophy. The β isoform of PKC (protein kinase C) is preferentially overexpressed in the myocardium of diabetic subjects accompanied with increased activation of the pro-oxidant enzyme NADPH oxidase, which may exacerbate oxidative stress. We hypothesized that myocardial PKCβ is a major upstream mediator of oxidative stress in diabetes and that PKCβ inhibition can attenuate myocardial hypertrophy and dysfunction. Control or streptozotocin-induced diabetic rats were treated with the selective PKCβ inhibitor RBX (ruboxistaurin; 1 mg/kg of body weight per day) or the antioxidant NAC (N-acetylcysteine) for 4 weeks. LV (left ventricular) dimensions and functions were detected by echocardiography. 15-F2t-isoprostane (a specific index of oxidative stress) and myocardial activities of superoxide dismutase as well as protein levels of NADPH oxidase were assessed by immunoassay or Western blotting. Echocardiography revealed that the LV mass/body weight ratio was significantly increased in diabetic rats (P<0.01 compared with the control group) in parallel with the impaired LV relaxation. A significant increase in cardiomyocyte cross-sectional area was observed in diabetic rats accompanied by an increased production of O2− (superoxide anion) and 15-F2t-isoprostane (all P<0.05 compared with the control group). RBX normalized these changes with concomitant inhibition of PKCβ2 activation and prevention of NADPH oxidase subunit p67phox membrane translocation and p22phox overexpression. The effects of RBX were comparable with that of NAC, except that NAC was inferior to RBX in attenuating cardiac dysfunction. It is concluded that RBX can ameliorate myocardial hypertrophy and dysfunction in diabetes, which may represent a novel therapy in the prevention of diabetic cardiovascular complications.

scholarly journals Regression of gestational diabetes induced cardiomegaly in offspring of diabetic rat

2009 ◽  
Vol 24 (4) ◽  
pp. 251-255 ◽  
Author(s):  
Honório Sampaio Menezes ◽  
Cláudio Galeano Zettler ◽  
Alice Calone ◽  
Jackson Borges Corrêa ◽  
Carla Bartuscheck ◽  
...  
Keyword(s):  
Body Weight ◽  
Wistar Rats ◽  
Weight Ratio ◽  
Diabetic Rats ◽  
Heart Weight ◽  
Diabetic Rat ◽  
Control Group ◽  
Computer Assisted ◽  
Significant Difference ◽  
Levene Test

PURPOSE: To compare body weight and length, heart weight and length, heart-to-body weight ratio, glycemia, and morphometric cellular data of offspring of diabetic rats (ODR) and of normal rats (control). METHODS: Diabetes was induced in 3 pregnant Wistar rats, bearing 30 rats, on the 11th day after conception by intraperitoneal injection of 50 mg/kg of streptozotocin. Six normal pregnant Wistar rats, bearing 50 rats, made up the control group. Morphometric data were obtained using a scale for the weight, length, heart and body measurements. Morphometric cellular data were obtained by a computer assisted method applied to the measurements of myocytes. Statistical analysis utilized Student's t-test, ANOVA and Levene test. RESULTS: Control offspring had greater mean body weight and length than offspring of diabetic rats (p < 0.001). Heart weight and length and heart-to-body ratios of newborn rats differed between groups at birth (p < 0.001), but showed no difference at 21 days. Mean nuclei area and perimetric value of the myocytes decrees throughout the first 21 days of life (p < 0.01) in the diabetic group. CONCLUSIONS: Heart hypertrophy on the offspring of diabetic rats at birth was demonstrated by the significant difference between the groups. After the eleventh day, no difference was found, which confirmed regression of cardiomegaly. The significant difference between the first and the 21th day of life, for nuclei area feature, demonstrate regression of cardiac hypertrophy in the offspring of diabetic rats.

Cardiac vasculature and flow during pressure-overload hypertrophy

1986 ◽  
Vol 251 (5) ◽  
pp. H1031-H1037 ◽  
Author(s):  
E. A. Breisch ◽  
F. C. White ◽  
L. E. Nimmo ◽  
C. M. Bloor
Keyword(s):  
Blood Flow ◽  
Myocardial Blood Flow ◽  
Weight Ratio ◽  
Pressure Overload ◽  
Capillary Density ◽  
Left Ventricular ◽  
Control Group ◽  
Cross Sectional ◽  
Ventricle Hypertrophy ◽  
Aortic Cuff

The effects of pressure-overload hypertrophy (H) on myocardial blood flow and microvasculature were studied in the porcine left ventricle. Hypertrophy was produced in nine adult pigs by an aortic cuff constriction of the ascending aorta. Eight pigs served as controls. After 30 days the aortic cuff was released, and the hypertrophy group was studied 1 day postrelease. The degree of hypertrophy, determined by left ventricular-to-body weight ratio, was 45%. With hypertrophy, left ventricular blood flows were normal at rest. During exercise with adenosine infusion, myocardial blood flow to the endomyocardium was reduced compared with the control (C) group (H = 4.02 +/- 0.35, P less than 0.05; C = 5.33 +/- 0.41 ml X min-1 X g-1). Minimal coronary vascular resistance in the endomyocardium was increased during exercise with adenosine in the hypertrophy group compared with the control group. Anatomic studies revealed that hypertrophy causes a reduction in the endomyocardial capillary density (H = 1,654 +/- 168, P less than 0.025; C = 2,168 +/- 106, no./mm2) with a similar trend noted for the transmural arteriolar density. Arteriolar media wall cross-sectional area was unaffected by the pressure overload. These results indicate that changes in the vascular bed do not parallel myocyte growth during pressure-overload hypertrophy. The resultant anatomic imbalance compromises endomyocardial flow, making this region vulnerable to ischemia.

scholarly journals The Haematological Effects of Oleanolic Acid in Streptozotocin-Induced Diabetic Rats: Effects on Selected Markers

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Charity M. Baloyi ◽  
A. Khathi ◽  
Ntethelelo H. Sibiya ◽  
Phikelelani S. Ngubane
Keyword(s):  
Oxidative Stress ◽  
Oleanolic Acid ◽  
Blood Glucose Concentration ◽  
Glycated Haemoglobin ◽  
Diabetic Control ◽  
Cardiovascular Complications ◽  
Diabetic Rats ◽  
Control Group ◽  
Rbc Indices ◽  
Notable Increase

Background. Sustained hyperglycaemia leads to the development of haematological alterations which, if left untreated, is associated with cardiovascular complications. Insulin is the mainstay drug in type 1 diabetes mellitus (T1D); however, the use of insulin is associated with haematological alterations that could further worsen cardiovascular complications. Therefore, the aim of the study was to investigate the haematological effects of oleanolic acid (OA) in streptozotocin- (STZ-) induced diabetic rats. Methods. The animals were separated into five groups; the nondiabetic group (ND), the diabetic control group (DC), and the treatment groups of insulin (170 μg/kg, s.c), metformin (500 mg/kg, p.o), and OA (80 mg/kg, p.o). OA was administered orally twice a day. Thereafter, the animals were sacrificed, and blood and tissues were collected for haematological, hormonal, and oxidative status analysis. Results. Untreated diabetic rats exhibited hyperglycaemia, elevated glycated haemoglobin (HbA1c), oxidative stress, and a reduced erythropoietin (EPO) concentration when compared to ND rats. However, administration of OA attenuated hyperglycaemia, HbA1c, and EPO concentrations compared to DC rats. The reduction of blood glucose concentration, HbA1c, and improved EPO concentrations was further associated with a notable increase in red blood cell (RBC) count and other RBC indices. We also observed an increase in the antioxidant status of the RBCs with a concomitant decrease in oxidative stress. Conclusion. These findings suggest that OA improves diabetes-induced haematological changes caused by hyperglycaemia and attenuates the progression of cardiovascular complications in DM individuals.

scholarly journals Effects of Rosiglitazone with Insulin Combination Therapy on Oxidative Stress and Lipid Profile in Left Ventricular Muscles of Diabetic Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Servet Kavak ◽  
Lokman Ayaz ◽  
Mustafa Emre
Keyword(s):  
Oxidative Stress ◽  
Blood Glucose ◽  
Lipid Profile ◽  
Nitrosative Stress ◽  
Vascular Diseases ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Control Group ◽  
Group B ◽  
Group D

Purpose. In this study, we tested the hypothesis that rosiglitazone (RSG) with insulin is able to quench oxidative stress initiated by high glucose through prevention of NAD(P)H oxidase activation.Methods and Materials. Male albino Wistar rats were randomly divided into an untreated control group (C), a diabetic group (D) that was treated with a single intraperitoneal injection of streptozotocin (45 mgkg−1), and rosiglitazone group that was treated with RSG twice daily by gavage and insulin once daily by subcutaneous injection (group B). HbA1c and blood glucose levels in the circulation and malondialdehyde and 3-nitrotyrosine levels in left ventricular muscle were measured.Result. Treatment of D rats with group B resulted in a time-dependent decrease in blood glucose. We found that the lipid profile and HbA1c levels in group B reached the control group D rat values at the end of the treatment period. There was an increase in 3-nitrotyrosine levels in group D compared to group C. Malondialdehyde and 3-nitrotyrosine levels were found to be decreased in group B compared to group D(P<0.05).Conclusion. Our data suggests that the treatment of diabetic rats with group B for 8 weeks may decrease the oxidative/nitrosative stress in left ventricular tissue of rats. Thus, in diabetes-related vascular diseases, group B treatment may be cardioprotective.

scholarly journals ANTIHYPERGLYCEMIC AND ANTIOXIDATIVE EFFECTS OF LYGODIUM MICROPHYLLUM IN ALLOXAN INDUCED DIABETIC RATS

2018 ◽  
Vol 10 (12) ◽  
pp. 75
Author(s):  
D. G. Syahidah Nadiah Binti Abdull Majid ◽  
Mohammad Iqbal
Keyword(s):  
Oxidative Stress ◽  
Body Weight ◽  
Blood Glucose ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
Control Group ◽  
Oxidative Stress Markers ◽  
Stress Markers ◽  
Antioxidative Effects ◽  
And Oxidative Stress

Objective: The antihyperglycemic and antioxidative effects of L. microphyllum were evaluated by using in vivo methods in normal and alloxan induced diabetic rats.Methods: Diabetes was induced in Sprague Dawley rats by injecting alloxan through intravenous (i. v) at a dose of 100 mg/kg of body weight. Aqueous extract of L. microphyllum at different doses (400, 200 and 100 mg/kg of body weight) was administered orally (orogastric intubation) for 14 d. Blood glucose and oxidative stress markers were measured. Hematoxylin and eosin staining method were used to examine the pancreatic tissues.Results: At the 14 d interval, fasting blood glucose showed a reduction in serum glucose levels in animals pretreated with L. microphyllum compared with alloxan alone treated group. Oxidative stress was noticed in rat’s pancreatic tissue as evidenced by a significant decrease in glutathione level, glutathione reductase, glutathione-S-transferase, and catalase activities. Malondialdehyde showed a significant increase compared to the normal saline-treated control group. Serum biochemistry and oxidative stress markers were consistent with the pancreatic histopathological studies. Treatment of diabetic rats with L. microphyllum at a dose level of 100, 200 and 400 mg/kg body weight leaves extract for 14 d significantly prevented these alterations and attenuated alloxan-induced oxidative stress (P<0.05).Conclusion: The results of the present study indicated that the antihyperglycemic potential of L. microphyllum might be ascribable to its antioxidant and free radical scavenging properties. Thus, it is concluded that L. microphyllum may be helpful in the prevention of diabetic complications associated with oxidative stress.

Genistein prevents isoproterenol-induced cardiac hypertrophy in rats

2012 ◽  
Vol 90 (8) ◽  
pp. 1117-1125 ◽  
Author(s):  
Subir Kumar Maulik ◽  
Pankaj Prabhakar ◽  
Amit Kumar Dinda ◽  
Sandeep Seth
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Body Weight ◽  
Nitric Oxide Synthase ◽  
Cardiac Hypertrophy ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Heart Weight ◽  
Once Daily ◽  
Oxide Synthase

Genistein, an isoflavone and a rich constituent of soy, possesses important regulatory effects on nitric oxide (NO) synthesis and oxidative stress. Transient and low release of NO by endothelial nitric oxide synthase (eNOS) has been shown to be beneficial, while high and sustained release by inducible nitric oxide synthase (iNOS) may be detrimental in pathological cardiac hypertrophy. The present study was designed to evaluate whether genistein could prevent isoproterenol-induced cardiac hypertrophy in male Wistar rats (150–200 g, 10–12 weeks old) rats. Isoproterenol (5 mg·(kg body weight)–1) was injected subcutaneously once daily for 14 days to induced cardiac hypertrophy. Genistein (0.1 and 0.2 mg·kg–1, subcutaneous injection once daily) was administered along with isoproterenol. Heart tissue was studied for myocyte size and fibrosis. Myocardial thiobarbituric acid reactive substances (TBARS), glutathione (GSH), superoxide dismutase (SOD), catalase levels, and 1-OH proline (collagen content) were also estimated. Genistein significantly prevented any isoproterenol-induced increase in heart weight to body weight ratio, left ventricular mass (echocardiographic), myocardial 1-OH proline, fibrosis, myocyte size and myocardial oxidative stress. These beneficial effects of genistein were blocked by a nonselective NOS inhibitor (L-NAME), but not by a selective iNOS inhibitor (aminoguanidine). Thus, the present study suggests that the salutary effects of genistein on isoproterenol-induced cardiac hypertrophy may be mediated through inhibition of iNOS and potentiation of eNOS activities.

scholarly journals Efficacy of Shear Wave Elasticity for Evaluating Myocardial Hypertrophy in Hypertensive Rats

2021 ◽  
Author(s):  
Yoichi Takaya ◽  
Kazufumi Nakamura ◽  
Rie Nakayama ◽  
Ohtsuka Hiroaki ◽  
Naofumi Amioka ◽  
...  
Keyword(s):  
Shear Wave ◽  
Myocardial Hypertrophy ◽  
Interventricular Septum ◽  
Left Ventricular ◽  
Cross Sectional Area ◽  
Control Group ◽  
Sectional Area ◽  
Hypertensive Rats ◽  
Cross Sectional ◽  
The Cross

Abstract Shear wave (SW) imaging is a novel ultrasound-based technique for assessing tissue characteristics. SW elasticity may be useful to assess the severity of hypertensive left ventricular (LV) hypertrophy. This study aimed to evaluate the efficacy of SW elasticity for assessing the degree of myocardial hypertrophy using hypertensive rats. Rats were divided into hypertension group and control group. SW elasticity was measured on the excised heart. Myocardial hypertrophy was assessed histologically. LV weight was greater in hypertension group. An increase in interventricular septum and LV free wall thicknesses was observed in hypertension group. SW elasticity was significantly higher in hypertension group than in control group (14.6 ± 4.3 kPa vs. 6.5 ± 1.1 kPa, P < 0.01). The cross-sectional area of cardiomyocytes was larger in hypertension group than in control group (397 ± 50 µm2 vs. 243 ± 14 µm2, P < 0.01), and SW elasticity was positively correlated with the cross-sectional area of cardiomyocytes (R = 0.96, P < 0.01). This study showed that SW elasticity was higher in hypertensive rats and was closely correlated with the degree of myocardial hypertrophy, suggesting the efficacy of SW elasticity for estimating the severity of hypertensive LV hypertrophy.

Abstract 2: Mesenchymal Stem Cell Therapy Prevented Doxorubicin Induced Cardiac Dysfunction in Diabetics Rats

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Sanjiv Dhingra ◽  
Hania Ibrahim Ammar ◽  
Mira Barsoum Nashed ◽  
Rasha Ibrahim Ammar ◽  
Hala Gabr ◽  
...  
Keyword(s):  
Body Weight ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cardiac Function ◽  
Cardiac Dysfunction ◽  
Pressure Rise ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Control Group ◽  
Tail Vein

Background: It is now established that having diabetes not only increases the chances of cancer also it complicates cancer treatment therapy. Doxorubicin (DOX) is a well known anticancer drug, however the clinical use of DOX was limited due to its cardiotoxic effects. One of the major concerns with DOX therapy has been its toxicity in patients who are less robust and more prone to toxic side effects, particularly patients with comorbid diseases such as diabetes mellitus. Several studies have demonstrated that mesenchymal stem cell (MSC) therapy has the potential to restore cardiac function following DOX induced cardiac injury. However, there is no study available on the effects of MSC therapy on DOX induced cardiac dysfunction in diabetics. Methods and Results: Diabetes was induced in male Wistar rats by streptozotcin injection (STZ, 65mg/kg body weight, i.p.). After 4 weeks of STZ injection, blood glucose levels in STZ group (301.58±23.97mg/dl) were significantly greater than control group (83.51±7.91mg/dl). These diabetic rats were treated with adriamycin (2.5mg/kg body weight, i.p) 3 times/week for two weeks (AD group); or with adriamycin+bone marrow MSCs (BM-MSC; 2x106 cells, via tail vein) or with adriamycin+adipose tissue derived MSCs (AD-MSC; 2x106 cells, via tail vein). Echocardiographic measurements showed a significant decline in cardiac function (%EF) following adriamycin treatment. Both BM-MSC and AT-MSC treatment improved %EF at 4 weeks. After 4 weeks of MSC injection, hearts from all the groups were excised and subjected to retrograde Langendorff perfusion and baseline levels of left ventricular developed pressure (LVDP), maximum rate of pressure rise dp/dt max and rate pressure product (RPP) were recorded. AD treatment caused a significant decrease in LVDP, dp/dt max and RPP levels. Both BM-MSCs and AD-MSCs injection significantly improved all these parameters. Conclusion: Both BM-MSC and AT-MSC were equally effective in preventing deterioration of cardiac function following doxorubicin therapy in diabetic rats. Furthermore, these findings should act as a stimulus for further research on the benefits of MSC therapy for diabetic subjects suffering from cancer.

scholarly journals Modulatory effects of garlic, ginger, turmeric and their mixture on hyperglycaemia, dyslipidaemia and oxidative stress in streptozotocin–nicotinamide diabetic rats

2010 ◽  
Vol 105 (8) ◽  
pp. 1210-1217 ◽  
Author(s):  
Hafez R. Madkor ◽  
Sherif W. Mansour ◽  
Gamal Ramadan
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Body Weight ◽  
Antioxidant Activities ◽  
Cardiovascular Complications ◽  
Diabetic Rats ◽  
The Metabolic Syndrome ◽  
Atherogenic Indices ◽  
Antioxidant Defence System ◽  
And Oxidative Stress

Spices which show hypoglycaemic, hypolipidaemic and antioxidant activities may have a role in the treatment of diabetes and its complications. The present study aimed to compare the modulatory effects of garlic, ginger, turmeric and their mixture on the metabolic syndrome and oxidative stress in streptozotocin (STZ)–nicotinamide diabetic rats. Diabetes was induced in overnight fasted rats by a single intraperitoneal injection of STZ (65 mg/kg body weight) and nicotinamide (110 mg/kg body weight, 15 min before STZ injection). Diabetic rats orally received either distilled water (as vehicle) or 200 mg/kg body weight of garlic bulb, ginger rhizome or turmeric rhizome powder suspension separately or mixed together (GGT mixture) for twenty-eight consecutive days. The results showed that these spices and their mixture significantly alleviated (80–97 %,P < 0·05–0·001) signs of the metabolic syndrome (hyperglycaemia and dyslipidaemia), the elevation in atherogenic indices and cellular toxicity in STZ–nicotinamide diabetic rats by increasing the production of insulin (26–37 %), enhancing the antioxidant defence system (31–52 %, especially GSH) and decreasing lipid peroxidation (60–97 %). The greatest modulation was seen in diabetic rats that received garlic and the GGT mixture (10–23 % more than that in the ginger and turmeric groups). In conclusion, garlic or the mix including garlic appears to have an impact on each of the measures more effectively than ginger and turmeric and may have a role in alleviating the risks of the metabolic syndrome and cardiovascular complications.

scholarly journals Low Intensity Physical Exercise Attenuates Cardiac Remodeling and Myocardial Oxidative Stress and Dysfunction in Diabetic Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
C. Gimenes ◽  
R. Gimenes ◽  
C. M. Rosa ◽  
N. P. Xavier ◽  
D. H. S. Campos ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Left Atrium ◽  
Cardiac Remodeling ◽  
Myocardial Function ◽  
Lipid Hydroperoxide ◽  
Weight Ratio ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Low Intensity ◽  
Myocardial Oxidative Stress

We evaluated the effects of a low intensity aerobic exercise protocol on cardiac remodeling and myocardial function in diabetic rats. Wistar rats were assigned into four groups: sedentary control (C-Sed), exercised control (C-Ex), sedentary diabetes (DM-Sed), and exercised diabetes (DM-Ex). Diabetes was induced by intraperitoneal injection of streptozotocin. Rats exercised for 9 weeks in treadmill at 11 m/min, 18 min/day. Myocardial function was evaluated in left ventricular (LV) papillary muscles and oxidative stress in LV tissue. Statistical analysis was given by ANOVA or Kruskal-Wallis. Echocardiogram showed diabetic groups with higher LV diastolic diameter-to-body weight ratio and lower posterior wall shortening velocity than controls. Left atrium diameter was lower in DM-Ex than DM-Sed (C-Sed:5.73±0.49; C-Ex:5.67±0.53; DM-Sed:6.41±0.54; DM-Ex:5.81±0.50 mm;P<0.05DM-Sed vs C-Sed and DM-Ex). Papillary muscle function was depressed in DM-Sed compared to C-Sed. Exercise attenuated this change in DM-Ex. Lipid hydroperoxide concentration was higher in DM-Sed than C-Sed and DM-Ex. Catalase and superoxide dismutase activities were lower in diabetics than controls and higher in DM-Ex than DM-Sed. Glutathione peroxidase activity was lower in DM-Sed than C-Sed and DM-Ex.Conclusion.Low intensity exercise attenuates left atrium dilation and myocardial oxidative stress and dysfunction in type 1 diabetic rats.

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