Heart Tissue Of Diabetic Rats Research Articles

Ameliorative Effect of Ginger on Blood Glucose Levels and Cardiac TCA Cycle Enzymes Activity in STZ Induced Diabetic Rat

This study aimed to investigate the effects of ginger administration on altered blood glucose levels, cytosolic and mitochondrial enzymes (TCA cycle enzymes) activity in streptozotocin-induced diabetes rats. The study divided Wistar strain rats into five groups: normal control, ginger treated, diabetic control, diabetic plus ginger treated, and diabetic plus glibenclamide treated groups. The diabetic group had significantly elevated blood glucose levels, which were significantly lowered by ginger administration. The cytosolic enzyme G6PDH activity was significantly (P<0.001) decreased along with a significant increase in the LDH activity in diabetic rats heart tissue. The activities of SDH, MDH, GDH in the heart tissue of diabetic rats were significantly decreased, but the daily oral treatment of ginger to diabetic rats for thirty days reversed the above changes in a significant (P<0.001) manner. The study demonstrated that an ethanolic extract of ginger could lower blood glucose levels, improve enzyme activities and body weight in diabetic rats. This suggests that ginger extracts could be used as a cardio-protective supplement to reverse diabetic-induced complications.

The Effect of Eight Weeks of High-Intensity Interval Training with L-Cysteine Consumption on CRP and TNF-α in Heart Tissue of Young Rats with Type 2 Diabetes

Background: This study aimed to investigate the effect of 8-weeks of high-intensity interval training (HIIT) with L-cysteine consumption on tumor necrosis factor-alpha (TNF-α) and C-reactive protein (CRP) of heart tissue in young rats with type 2 diabetes. Methods: The statistical population of the present study consisted of young (4 months) rats with type 2 diabetes. Ten rats were selected as a healthy group, and 40 rats became diabetic. Diabetic rats were randomly divided into four groups: diabetes control, diabetics with training, diabetics with supplements, and diabetics with training+supplement. Moreover, high-intensity interval exercises were performed 3 days a week for 8 weeks, and 500 micromoles of L-cysteine were administered daily. Results: The training+supplement group had significantly higher TNF-α levels compared to the diabetic control group (P=0.002). The diabetic control group (P=0.001) and training group (P=0.001) had higher TNF-α levels compared to the healthy control. The supplement group had significantly less TNF-α compared to the diabetic control group (P=0.003), while the supplement group (P=0.019) and the training+supplement group (P=0.013) had lower TNF-α levels compared to the training group. Moreover, the training+supplement group had lower CRP levels compared to the diabetic control group (P=0.001), while the diabetic control (P=0.001), exercise (P=0.002), and supplement group (P=0.031) had higher CRP levels compared to the healthy control. Moreover, the training group (P=0.038) and the supplement group (P=0.002) had lower CRP compared to the diabetic control group. Furthermore, the training+supplement group had a lower CRP level compared to the training group (P=0.03). Conclusion: HIIT along with the L-cysteine consumption reduced TNF-α and CRP in the heart tissue of diabetic rats.

MiR-34a/SIRT1/HIF-1α axis is involved in cardiac angiogenesis of type 2 diabetic rats: The protective effect of sodium butyrate combined with treadmill exercise.

Type 2 diabetes mellitus (T2DM) is one of the most common metabolic disorders worldwide. Recent research has indicated that sodium butyrate (NaB) affects glucose metabolism and exercise has an anti-hyperglycemic effect in diabetes. This study aimed to evaluate the effects of NaB and treadmill exercise on heart angiogenesis through the miR-34a/SIRT1/FOXO1-HIF-1α pathway. Diabetic animals received NaB (400 mg/kg daily, orally) and treadmill exercise for 6 weeks. The effect of NaB and treadmill exercise, alone or combined, on miR-34a expression, SIRT1, FOXO1, HIF-1α levels, and angiogenesis in diabetic heart tissue was measured. Diabetes caused increased miR-34a (p < 0.01) and FOXO1 (p < 0.001) expression levels. Also, SIRT1 (p < 0.001) and HIF-1α (not significant) expression levels were reduced in diabetic rats. NaB and treadmill exercise decreased miR-34a (respectively p < 0.05 and not significant) and FOXO1 (both p < 0.001) expression levels and improved SIRT1 (both not significant) and HIF-1α (respectively p < 0.01 and p < 0.001) levels. Also, NaB combined with treadmill exercise decreased miR-34a (p < 0.001) and FOXO1 (p < 0.001) expression levels, and elevated SIRT1 (p < 0.05) and HIF-1α (p < 0.001) levels in comparison with the diabetic group. NaB and treadmill exercises modulate the expression of miR-34a and the levels of SIRT1, FOXO1, and HIF-1α proteins, thus increasing angiogenesis in the heart tissue of diabetic rats. It can be concluded that NaB and treadmill exercise, alone or combined, may be useful in the treatment of diabetes through the miR-34a/SIRT1/FOXO1-HIF-1α pathway.

TRPA1 deficiency attenuates cardiac fibrosis via regulating GRK5/NFAT signaling in diabetic rats

BackgroundTransient receptor potential ankyrin 1 (TRPA1) has been linked to the development of various cardiovascular diseases, but its role in diabetic cardiomyopathy is not well understood. This study aimed to investigate the protective effects of TRPA1 deficiency on diabetic cardiomyopathy in rats with streptozotocin-induced diabetes and in neonatal rat cardiac fibroblasts (CFs) exposed to high glucose (HG). MethodsCardiac TRPA1 expression levels were measured in diabetic rats. Cardiac function, remodeling, and fibrosis were analyzed in Sprague-Dawley (SD) rats and TRPA1-deficient rats with diabetic cardiomyopathy. In vitro, fibrosis was measured in CFs exposed to HG. Additionally, 1,8-cineole, a natural inhibitor of TRPA1, was used to treat SD rats with diabetic cardiomyopathy. ResultsTRPA1 expression was increased in the heart tissue of diabetic rats and in CFs treated with HG. TRPA1 deficiency significantly improved cardiac function in diabetic rats, as evidenced by improved echocardiography and reduced cardiac hypertrophy and fibrosis. In vitro, TRPA1 deficiency suppressed the transformation of HG-induced CFs into myofibroblasts. The cardioprotective effect of TRPA1 deficiency was found to inhibit cardiac fibrosis by regulating GRK5/NFAT signaling. Furthermore, inhibition of GRK5/NFAT signaling abolished the promotion of CF transformation into myofibroblasts by TRPA1 activation. Inhibition of TRPA1 activation by 1,8-cineole reduced cardiac dysfunction and remodeling in diabetic rats by regulating GRK5/NFAT signaling. ConclusionsTRPA1 deficiency reduced cardiac fibrosis in diabetic rats and inhibited HG-induced CF activation in vitro by regulating GRK5/NFAT signaling. The TRPA1 inhibitor 1,8-cineole may serve as a novel therapeutic agent for the treatment of diabetic cardiomyopathy.

The Effect of Endurance and Resistance Training on Apoptosis Activity and Collagen Deposition in Heart Tissue of Diabetic Rats

The Effect of Endurance and Resistance Training on Apoptosis Activity and Collagen Deposition in Heart Tissue of Diabetic Rats

Protective effects of tropisetron on diabetes-induced cardiomyopathy and apoptosis in the left ventricle of rats

Tropisetron, an antagonist of 5-HT3 receptor (5-HT3R), has exhibited a number of beneficial effects on the treatment of several diseases; however, its effect on diabetic cardiomyopathy, which is an important causal factor in morbidity and mortality among diabetic patients, remains to be fully elucidated. Therefore, this study was designed to investigate the effect of tropisetron on diabetes-induced cardiomyopathy and the molecular mediators possibly involved. Twenty-four male wistar rats were assigned into three groups, control, diabetic, and tropisetron–treated diabetic groups. After 14 days of treatment, the results revealed a significant increase in calcium/calmodulin-dependent protein kinaseIIδ (CaMKIIδ) total and isoforms δ2 and δ3 of CaMKIIδ, as well as myosin heavy chain (MHC)-β. Furthermore, it decreased MHC-α gene expression among the diabetic group compared to the control group. Western blot analysis showed a significant increase in Bax and cleaved caspase 3 protein levels and a significant decrease in Bcl-2 contents in heart tissue of diabetic rats in comparison to the control rats. Moreover, the levels of Tumor necrosis factor alpha (TNF-α), ICAM-1, and CaMKII in heart tissue of diabetic rats were significantly higher than those in the control rats. Significant amelioration of alteration in the genes expression and protein changes along with restoration of the elevated levels of TNF-α, ICAM-1, and CaMKII were found in the tropisetron–treated diabetic group compared to the diabetic group. Collectively, our study provided strong evidence that 5-HT3 antagonist tropisetron was capable of attenuating the development of experimental diabetic cardiomyopathy associated with the reduction of intramyocardial MHCs and CaMKIIδ gene expression, inflammation and cardiac hypertrophy.

N-Acetyl Cysteine, Selenium, and Ascorbic Acid Rescue Diabetic Cardiac Hypertrophy via Mitochondrial-Associated Redox Regulators.

Metabolic disorders often lead to cardiac complications. Metabolic deregulations during diabetic conditions are linked to mitochondrial dysfunctions, which are the key contributing factors in cardiac hypertrophy. However, the underlying mechanisms involved in diabetes-induced cardiac hypertrophy are poorly understood. In the current study, we initially established a diabetic rat model by alloxan-administration, which was validated by peripheral glucose measurement. Diabetic rats displayed myocardial stiffness and fibrosis, changes in heart weight/body weight, heart weight/tibia length ratios, and enhanced size of myocytes, which altogether demonstrated the establishment of diabetic cardiac hypertrophy (DCH). Furthermore, we examined the expression of genes associated with mitochondrial signaling impairment. Our data show that the expression of PGC-1α, cytochrome c, MFN-2, and Drp-1 was deregulated. Mitochondrial-signaling impairment was further validated by redox-system dysregulation, which showed a significant increase in ROS and thiobarbituric acid reactive substances, both in serum and heart tissue, whereas the superoxide dismutase, catalase, and glutathione levels were decreased. Additionally, the expression levels of pro-apoptotic gene PUMA and stress marker GATA-4 genes were elevated, whereas ARC, PPARα, and Bcl-2 expression levels were decreased in the heart tissues of diabetic rats. Importantly, these alloxan-induced impairments were rescued by N-acetyl cysteine, ascorbic acid, and selenium treatment. This was demonstrated by the amelioration of myocardial stiffness, fibrosis, mitochondrial gene expression, lipid profile, restoration of myocyte size, reduced oxidative stress, and the activation of enzymes associated with antioxidant activities. Altogether, these data indicate that the improvement of mitochondrial dysfunction by protective agents such as N-acetyl cysteine, selenium, and ascorbic acid could rescue diabetes-associated cardiac complications, including DCH.

Effect of fangchinoline on oxidant status in male albino rats with streptozotocin-induced diabetes

Diabetes is a metabolic disorder caused by defects in insulin production and activity. During disease progression, changes in lipid peroxidation cause structural modifications via production of free radicals. Fangchinoline is a well-known alkaloid present in Stephaniae tetrandrine S. Moore , which has demonstrated antioxidant, anticancer, and anti-inflammatory activities. The present study analyzed the anti-diabetic and antioxidant effects of fangchinoline in male rats with streptozotocin-induced diabetes. Rats were divided into the following groups: normal control, diabetic, diabetic + fangchinoline 100 mg/kg, diabetic + fangchinoline 200 mg/kg and diabetic + glibenclamide 600 µg/kg. The treatment was administered orally for 45 consecutive days. Lipid peroxidation was substantially increased by >50% in the serum, as well as the liver, kidney, and heart tissues of diabetic rats. However, fangchinoline supplementation significantly reduced lipid peroxidation to near normal levels. Reactive oxygen species levels were substantially increased by >500% in the serum, as well as the liver, kidney, and heart tissues of diabetic rats. Fangchinoline supplementation reduced reactive oxygen species to near normal levels. Fangchinoline supplementation significantly improved superoxide dismutase, glutathione peroxidase, catalase, and reduced glutathione levels in diabetic rats. Total hexoses, sialic acid, hexosamines, and fucose were increased in diabetic rats, whereas fangchinoline supplementation significantly reduced these total hexoses, sialic acid, hexosamines, and fucose to near normal levels Supplementation with fangchinoline led to significant attenuation of the levels of lipid peroxidation, ROS, and glycoprotein components such as total hexoses, hexosamines, sialic acid, and fucose, while improving antioxidant marker levels. How to cite: Xia J, Huang W, Zhou F. Effect of fangchinoline on oxidant status in male albino rats with streptozotocin-induced diabetes. Electron J Biotechnol 2021;53. https://doi.org/10.1016/j.ejbt.2021.07.005

The Comparison of Antioxidant Effect of Aspirin, Metformin, Atorvastatin and Captopril Co-administration in the Heart and Kidney Tissues of Diabetic Rats.

The present study investigated the effects of co-administration of aspirin, metformin, atorvastatin and captopril on serum lipid profile and oxidative stress in the heart and kidney of streptozotocin-induced diabetic rats. In this study, rats were randomly divided into the following eleven groups: control (Cont.), and diabetic (D), as well as 9 groups that were treated with metformin (M, 300 mg/kg) or aspirin (ASA, 120 mg/kg) alone or in different combinations with captopril (C, 50 mg/kg), or atorvastatin (AT, 40 mg/kg), as follows: (D + M), (D + ASA), (D + M + ASA), (D + M + C), (D + M + AT), (D + M + C + ASA), (D + M + C + AT), (D + M + AT + ASA), and (D + M + C + AT + ASA). The rats in treatment groups daily received drugs by gavage for six weeks. Finally, serum lipid profile and levels of oxidative markers in the heart and kidney tissues were evaluated. In diabetic rats, blood levels of glucose, cholesterol, TG (triglyceride), LDL (low-density lipoprotein), MDA (malondialdehyde) and AIP (atherogenic index of plasma) significantly increased but those of HDL (high-density lipoprotein) and total thiol as well as SOD (superoxide dismutase) and CAT (catalase) activities significantly decreased. Treatment with different combinations of C, ASA, AT and M significantly ameliorated these parameters. This study showed that co-administration of ASA, M, C and AT, could improve glucose and lipid metabolism and oxidative stress markers in the kidneys and heart tissues of diabetic rats more markedly than the administration of these drugs alone.

Modulation of hydrogen sulfide synthesis improves heart function and endothelium-dependent vasorelaxation in diabetes.

Diabetes dramatically increases the risk of cardiovascular complications. The endothelial dysfunction and diastolic heart dysfunction are associated with a decreasing level of hydrogen sulfide (H2S) and inhibition of the activity of endothelial nitric oxide synthase (NOS) in diabetes. The aim of this study is to investigate the effect of modulation of H2S synthesis on heart functions and vasorelaxation in diabetes. The dl-propargylglycine and l-cysteine were administered intraperitoneally. H2S content in the heart tissue, markers of oxidative stress, inducible NOS and constitutive NOS (cNOS) activities, endothelium-dependent vasorelaxation of the aortic rings, and heart function were studied. We demonstrate that our combination increased H2S synthesis 13 times and cNOS activity 5 times in the heart tissue of diabetic rats. Increasing NO and H2S production caused improvement and restoration of endothelium-dependent relaxation of aorta, effective arterial elastance, and diastolic heart function in diabetic rats. The endothelium-dependent relaxation increased 2.4 times; effective arterial elastance decreased by 47%. The end-diastolic myocardial stiffness decreased 2.2 times. Thus, modulation of H2S synthesis leads to increased cNOS activity by up to 5 times in the cardiovascular system. Increasing NO and H2S production restored endothelium-dependent relaxation of aorta and improved heart function in diabetes.

Aerobic exercise leads to upregulation of Mir-126 and angiogenic signaling in the heart tissue of diabetic rats

ObjectiveMicroRNA-126 plays a critical role in promoting cardiac angiogenesis. Aerobic exercise has also cardioprotective effects by upregulating angiogenic factors. The present study aimed to evaluate the impact of aerobic exercise on cardiac expression of mir-126 and angiogenic signaling pathways. MethodsThirty-two male Wistar rats (180–240 g) were randomly divided into four diabetic control, healthy control, healthy exercise, and diabetic exercise groups. Diabetes was induced by intraperitoneal injection of Streptozotocin (STZ) 50 mg/kg (with citrate buffer) and nicotinamide 110 mg/kg (with saline). Aerobic training groups were performing on a rodent treadmill with an intensity of 25 m/min, 5° gradients, and 30 min each session for 8 weeks. The control groups were placed on a stationary treadmill without training. The heart of the rats was taken and the expression level of cardiac mir-126 was evaluated by Real-time PCR. The protein levels of raf1, spred1, and VEGF were measured using ELISA. Immunohistochemistry was used to measure cardiac muscle capillary density. ResultsThe results showed that diabetes induced by STZ disrupted angiogenesis signaling through the reduction of mir-126, raf1, and VEGF, while an increase in spred1 protein level (p = 0.01 for all). However, 8 weeks of aerobic exercise (in healthy animals) significantly increased mir-126 expression, and raf1 and VEGF proteins (p = 0.05), while significantly decreased spred1 protein (p = 0.05). Also, 8 weeks of exercise training in diabetic rats might improve the cardiac tissue by increasing mir-126 and angiogenic signaling pathways. ConclusionThe results of this study suggest that aerobic exercise training may prevent negative effects of diabetes on heart tissue by improving angiogenic pathway. Therefore, aerobic exercise may be a good strategy for coping with cardiovascular cell damage of diabetes.

Lycium barbarum polysaccharide attenuates cardiac hypertrophy, inhibits calpain-1 expression and inhibits NF-κB activation in streptozotocin-induced diabetic rats.

Cardiac hypertrophy is one of the key structural changes that occurs in diabetic cardiomyopathy. Previous studies have indicated that the activation of NF-κB by calpain-1, a Ca2+-dependent cysteine protease, serves an important role in cardiac hypertrophy. The aim of the present study was to assess the effect of 30 and 60 mg/kg Lycium barbarum polysaccharide (LBP) treatment, the major active ingredient extracted from Lycium barbarum, on cardiac hypertrophy in streptozotocin (STZ) induced diabetic rats. In addition, the present study examined the possible underlying mechanisms of this effect by assessing calpain-1 expression and the NF-κB pathway. The mRNA expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) was determined by reverse transcription-quantitative PCR. Western blotting was used to detect the protein expressions of calpain-1, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1) and toll-like receptor-4 (TLR-4) in the heart tissue. The results revealed that compared with non-diabetic rats, diabetic rats exhibited cardiac hypertrophy. Cardiac hypertrophy was defined by the following: Dysfunction of the cardiac hemodynamics, an increase in the ratios of left ventricular weight/body weight and heart weight/body weight and the increased expressions of ANP and BNP, which serve as hypertrophic markers in cardiac tissue. However, all of these changes were attenuated in diabetic rats treated with LBP. In addition, the protein expression of calpain-1 was increased in the heart tissue of diabetic rats compared with that of non-diabetic rats, where it was inhibited by LBP. LBP also decreased the protein expression of certain inflammatory mediators, IL-6, TNF-α, ICAM-1, VCAM-1 and TLR-4 in diabetic heart tissue. Furthermore, LBP treatment reduced the production of reactive oxygen species, upregulated the protein expression of endothelial nitric oxide synthase and downregulated the protein expression of inducible nitric-oxide synthase. Additionally, LBP increased the protein expression of p65, the subunit of NF-κB and inhibitory protein кB-α in the cytoplasm and reduced p65 expression in the nucleus. In conclusion, LBP improves cardiac hypertrophy, inhibits the expression of calpain-1 and inhibits the activation of NF-κB in diabetic rats.

Effects of IMOD™ on angiogenesis, miR-503 and CDC25 expression levels in heart tissue of diabetic male rats.

Diabetes is associated with vascular complications and impaired angiogenesis. Since angiogenesis plays a crucial role in vascular homeostasis in ischemic heart diseases, in this study, the effect of IMOD™ on miR-503 and CDC25 expression level which are altered in impaired angiogenesis were investigated in heart tissue of diabetic rats. Forty male Wistar rats (200-250 g) were randomly classified into 4 groups: control (C), IMOD™ (I), diabetes (D), and diabetes+IMOD™ (D+I). For induction of experimental diabetes in animals, a single dose of streptozotocin (STZ; 60mg/kg) was injected intraperitoneally. After 8 weeks of treatment with IMOD™ (20 mg/kg/day), heart tissue samples were removed and used for measurement of miR-503 and CDC25 expression level as well as histological studies. Results of this study showed that diabetes decreased heart tissue angiogenesis which was associated with increased miR-503 and reduced CDC25 expression levels (p<0.05) and IMOD™ could reduce the expression of miR-503 and increase the expression of CDC25 (p<0.05). Moreover, IMOD™ extensively induced angiogenesis in the heart tissue of diabetic group. However, IMOD™ had no significant effect on expressions of miR-503 and CDC25, or angiogenesis in healthy rats. This study showed that IMOD™ is able to increase angiogenesis in the heart tissue of diabetic rats. The angiogenic effect of IMOD™ is associated with reduction of miR-503 expression and increased expression of CDC25.

Curcumin administration suppresses collagen synthesis in the hearts of rats with experimental diabetes.

Cardiac fibrosis is considered the initial change of diabetic cardiomyopathy (DCM). We have shown that curcumin alleviates collagen deposition in DCM, but the mechanism remains unknown. In this study we sought to investigate the effects of curcumin on cardiac fibrosis in vivo and in vitro and to elucidate the underlying mechanisms. Experimental diabetes was induced in rats by injection of low-dose streptozotocin (STZ) combined with high energy diet. The rats were orally treated with curcumin (300 mg·kg-1·d-1) for 16 weeks. Curcumin administration significantly suppressed the deposition of type I and type III collagens in the heart tissues of diabetic rats, accompanied by markedly reduced TGF-β1 production, suppressed TβR II levels and Smad2/3 phosphorylation, and increased Smad7 expression. Similar effects were observed in human cardiac fibroblasts exposed to high glucose (HG, 30 mmol/L) or exogenous TGF-β1 (5 ng/mL). Furthermore, TGF-β1 or HG treatment significantly increased the phosphorylation levels of AMPK and p38 MAPK in the fibroblasts. Application of curcumin (25 μmol/L) inhibited TGF-β1- or HG-induced AMPK/p38 MAPK activation and suppressed collagen synthesis in the fibroblasts. These effects were similar to those of the AMPK inhibitor compound C (10 μmol/L) but opposite to the effects of the AMPK activator metformin (2 mmol/L) in the fibroblasts. Our results demonstrate that curcumin suppresses diabetes-associated collagen synthesis in rat myocardium not only by inhibiting TGF-β1 production and canonical Smad signaling but also by blocking the non-canonical AMPK/p38 MAPK pathway.

HPLC-DAD-QTOF-MS profiling of phenolics from leaf extracts of two Tunisian fig cultivars: Potential as a functional food.

The phenolic constituents of the aqueous-ethanolic extract of two Tunisian Ficus carica leaves cultivars and their hypoglycaemic, hypolipidaemic and antioxidative activities in alloxan-induced diabetic rats were investigated. Our results demonstrated that the treatment with the leaves extracts of F. carica improved lipid profile and reduced blood glucose level as well as thiobarbituric acid-reactive substances content. The antioxidant enzymes activity in the liver and heart tissues of diabetic rats was increased after the treatment. These antihyperglycaemic, antihyperlipidaemic and antioxidant effects of both leaf extracts could be associated with their in vitro scavenging ability and their phenolic composition. The HPLC-DAD-QTOF-MS analysis of both extracts revealed the presence of dihydroxybenzoic acid, dipentoside, rutin, psoralen, methoxypsoralen and oxypeudacin hydrate as relatively the most abundant compounds. These results showed indicated the capacity of the leaves extracts of F. carica to ameliorate hyperglycaemia, hyperlipidaemia and antioxidant status in diabetic rats.

CARDIOAMELIORATIVE EFFECT OF GALLIC ACID ON MYOCARDIAL INJURY ASSOCIATED WITH DIABETES INDUCED BY STREPTOZOTOCIN IN MALE RATS

Gallic acid (GA) is a natural antioxidant, which scavenges free radicals and protects against oxidative damage. This study was done to examine the effects of gallic acid in myocardial dysfunctions associated with diabetes. Diabetes mellitus type 1 (DMT1) was induced by a single intraperitoneal dose of streptozotocin (STZ, 45 mg/kg). As a result of induction of diabetes, the level of serum glucose, glycated hemoglobin (HbA-1c), homastatic-insulin resistance (HOMA-IR), troponin-T, lipid profiles, as well as the activity of lactate dehydrogenase (LDH) and creatine kinase-muscle bone (CK-MB) were increased. On the other hand, insulin and high-density lipoprotein (HDL) levels were decreased. In addition, the diabetic rats exhibited marked trend for increased malondialdehyde (MDA), hydrogen peroxide (H2O2), interlukin-1β (IL-1β), interlukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels, accompanied with decreased reduced glutathione (GSH) content, superoxide dismutase (SOD) and catalase (CAT) activities in the heart tissues. Furthermore, an increase in P53, Bax and caspase-9 in the heart tissues of diabetic rats was recorded, as well as a decline in Bcl2 level. On the other hand, diabetic rats which treated with GA orally at a dose of 25 mg/kg daily for 8 weeks, showed amelioration and improvement in the most tested parameters. The current results suggest that GA owns strong therapeutic potential in treating and regulating diabetes and attenuating its associated complications in the heart.

Voluntary Exercise Protects Heart from Oxidative Stress in Diabetic Rats.

Oxidative stress plays a key role in the onset and development of diabetes complications. In this study, we evaluated whether voluntary exercise could alleviate oxidative stress in the heart and blood of streptozotocin - induced diabetic rats. 28 male Wistar rats were randomly divided into four groups (n=7): control, exercise, diabetes and exercise + diabetes. Diabetes was induced by injection of streptozotocin in male rats. Rats in the trained groups were subjected to voluntary running wheel exercise for 6 weeks. At the end of six weeks blood and heart tissue samples were collected and used for determination of antioxidant enzymes (including SOD, GPX and CAT activities) and MDA level. Exercise significantly reduced MDA levels both in the heart tissue (p<0.01) and blood samples (p<0.05). In addition, exercise significantly increased SOD (p<0.05), GPX (p<0.001) and CAT (p<0.05) in the heart tissue. Voluntary exercise also significantly increased SOD (p<0.01), GPX (p<0.05) and CAT (p<0.001) in the blood. Voluntary exercise diminishes the MDA level in blood and heart tissue of diabetic rats. It also accentuates activities of SOD, GPX and CAT. Therefore, it may be considered a useful tool for the reduction of oxidative stress in diabetes.

Effect of L-arginine on the Expression of Endothelial Nitric Oxide Synthase (eNOS) in Heart Tissues of Diabetic Rats

Aims: This study aimed to determine the role of L - arginine on eNOS expression and its role on the level of some antioxidants as reduced glutathione and catalase in alloxan - induced diabetic rats. Study Design : Ninety adult male albino rats were divided into three (3) groups of thirty rats (30) each: Group (I): Control group, Group (II ) : Diabetic control group, Group (III): L - arginine treatment group. The secon d and the third group s were made diabetic by intraperitoneal administration of 80 mg/kg alloxan monohydrate , while L - arginine (100 mg/kg in sterile 0.9% Nacl) was given orally to rats in group III for one week before alloxan injection, and a further four weeks after induction of diabetes. The animal s were sacrificed and blood collected for the determination of biochemical and antioxidant ma rkers. Heart tissues were homogenized for determination of expression of eNOS gene by RT - PCR. Results: The study showed that L - arginine increases HDL, reduces glu tathione and catalase and decreases LDL, TAG, Cholesterol and MDA. It also increased the expression of eNOS in heart tissues of diabetic rats.

Oxidative Stress Plays Important Role on Cardiac Ryanodine Receptor Calcium Release Channels in Diabetic Rats

Reactive oxygen species play an important role in the development of diabetic cardiomyopathy due to alteration of Ca2+ signaling via changes in critical processes that regulate contractile activity of heart. Since these defects result partially from a dysfunction of cardiac ryanodine receptor calcium release channels (RyR2s), the present study was aimed to examine whether protective effect of in vivo administration of sodium selenate on contractile activity of heart from diabetic rats via affecting the hyperphosphorylation level of RyR2s and their a number of accessory proteins. Selenium normalized prolonged action potential duration and improved depressed tension obtained with electrically stimulated papillary muscle from diabetic rat hearts. Moreover, selenium reduced the increased oxidative stress and depressed oxtioxidant defence system in both plasma and heart tissue of diabetic rats. Western-blot data indicated that sodium selenate-treatment prevented markedly hyperphosphorylation of RyR2s, and activations of PKA, CaMKII and NF-κB as well as reduction in Trx level of the diabetic rat hearts. In the present study, we demonstrated that the mechanisms responsible for the cardioprotective effects of sodium selenate in the diabetic myocardium include preservation of oxidative stress-induced hyperphosphorylation and activation of Ca2+ signaling proteins, as well as with a normalization of NF-κB. Therefore, such an observation provides evidences for a potential therapeutic usage of selenium compounds in the amelioration of cardiovascular disorders in diabetes (Supported by TUBITAK SBAG-107S304).

Hypoglycemic activity and antioxidant potential of some medicinal plants traditionally used in Turkey for diabetes

Cydonia oblonga Mill. (Rosaceae) leaves, Helianthus tuberosus L. (Asteraceae) tubers, and Allium porrum L. (Liliaceae) bulbs are used as a folk remedy for the treatment of diabetes and they are also consumed as food in Turkey. In the present study, the antidiabetic and antioxidant activities of the ethanol extracts of these plants were studied in normal and streptozotocin-induced diabetic rats for 5 days. All extracts were administrated orally to rats at the doses of 250 and 500 mg/kg. Blood glucose level was measured according to glucose oxidase method. In order to determine antioxidant activity, thiobarbituric acid reactive substance (TBARS) and reduced glutathione (GSH) levels in liver, kidney, and heart tissues were measured by using spectrophotometric methods. Oral administration of Cydonia oblonga (500 mg/kg) and Allium porrum (500 mg/kg) extracts for 5 days in diabetic rats caused a decrease in blood glucose levels by 33.8% and 18.0%, respectively. Moreover, Allium porrum and Cydonia oblonga extracts induced significant alleviation on only heart tissue TBARS levels (44.6 and 45.7%), Helianthus tuberosus and Allium porrum extracts showed an inhibitory effect on kidney tissue TBARS levels (24.5 and 14.8%). None of the extracts restored GSH levels in kidney, liver, and heart tissues of diabetic rats.