scholarly journals CB2 receptor agonist and L- arginine combination attenuates diabetic cardiomyopathy in rats via NF-ĸβ inhibition

2021 ◽  
Author(s):  
Vivek S Kumawat ◽  
Ginpreet Kaur
Keyword(s):  
Oxidative Stress ◽  
Diabetic Cardiomyopathy ◽  
Receptor Activation ◽  
Diabetic Rats ◽  
Hemodynamic Parameters ◽  
Cb2 Receptor ◽  
No Donor ◽  
Cardiac Tissues ◽  
Cardiac Functions ◽  
Cytokine Levels

Beta-caryophyllene (BCP), a cannabinoid 2 receptor (CB2) agonist has recently been found to have cardioprotective activity as an anti-inflammatory and antioxidant molecule. L-arginine (LA), a nitric oxide (NO) donor is a potential regulator of cardiovascular function. Considering the role of CB2 receptor activation and NO regulation in cardiovascular diseases, the combination of BCP with LA may be a possible treatment of diabetic cardiomyopathy (DCM). Hence, we investigated the efficacy of the novel combination of BCP with LA on cardiovascular inflammation and oxidative stress in diabetic rats. DCM was induced by Streptozotocin (55 mg/kg) in SD rats intraperitoneally. BCP, LA and BCP with LA were administered to diabetic rats for 4 weeks. After completion of the study, hemodynamic parameters, biochemical parameters, and inflammatory cytokine levels were analyzed. Also, oxidative stress parameters, NF-ĸβ expression and histopathology in cardiac tissues were estimated. The combination of BCP (200 mg/kg) with LA (200 mg/kg) significantly normalized the hemodynamic parameters and decreased the glucose, cardiac markers, IL-6 and TNF-α levels. Treatment of BCP and LA showed a significant decrease in oxidative stress and down-regulated the cardiac expression of NF-ĸβ. Thus, the combination of BCP with LA improves cardiac functions by attenuating inflammation through NF-ĸβ inhibition in DCM.

Exercise and Stevia Rebaudiana (R) Extracts Attenuate Diabetic Cardiomyopathy in Type 2 Diabetic Rats: Possible Underlying Mechanisms

2020 ◽  
Vol 20 (7) ◽  
pp. 1117-1132
Author(s):  
Abdelaziz M. Hussein ◽  
Elsayed A. Eid ◽  
Ismaeel Bin-Jaliah ◽  
Medhat Taha ◽  
Lashin S. Lashin
Keyword(s):  
Oxidative Stress ◽  
Blood Glucose ◽  
Diabetic Cardiomyopathy ◽  
Caspase 3 ◽  
Stevia Rebaudiana ◽  
Diabetic Rats ◽  
Control Group ◽  
Underlying Mechanisms ◽  
Type 2 Diabetic

Background and Aims: In the current work, we studied the effects of exercise and stevia rebaudiana (R) extracts on diabetic cardiomyopathy (DCM) in type 2 diabetic rats and their possible underlying mechanisms. Methods: : Thirty-two male Sprague Dawley rats were randomly allocated into 4 equal groups; a) normal control group, b) DM group, type 2 diabetic rats received 2 ml oral saline daily for 4 weeks, c) DM+ Exercise, type 2 diabetic rats were treated with exercise for 4 weeks and d) DM+ stevia R extracts: type 2 diabetic rats received methanolic stevia R extracts. By the end of the experiment, serum blood glucose, HOMA-IR, insulin and cardiac enzymes (LDH, CK-MB), cardiac histopathology, oxidative stress markers (MDA, GSH and CAT), myocardial fibrosis by Masson trichrome, the expression of p53, caspase-3, α-SMA and tyrosine hydroxylase (TH) by immunostaining in myocardial tissues were measured. Results: T2DM caused a significant increase in blood glucose, HOMA-IR index, serum CK-MB and LDH, myocardial damage and fibrosis, myocardial MDA, myocardial α-SMA, p53, caspase-3, Nrf2 and TH density with a significant decrease in serum insulin and myocardial GSH and CAT (p< 0.05). On the other hand, treatment with either exercise or stevia R extracts significantly improved all studied parameters (p< 0.05). Moreover, the effects of stevia R was more significant than exercise (p< 0.05). Conclusion: Both exercise and methanolic stevia R extracts showed cardioprotective effects against DCM and Stevia R offered more cardioprotective than exercise. This cardioprotective effect of these lines of treatment might be due to attenuation of oxidative stress, apoptosis, sympathetic nerve density and fibrosis and upregulation of the antioxidant transcription factor, Nrf2.

scholarly journals Isosteviol ameliorates diabetic cardiomyopathy in rats by inhibiting ERK and NF-κB signaling pathways

2018 ◽  
Vol 238 (1) ◽  
pp. 47-60 ◽  
Author(s):  
Sheng-Gao Tang ◽  
Xiao-Yu Liu ◽  
Ji-Ming Ye ◽  
Ting-Ting Hu ◽  
Ying-Ying Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Glucose ◽  
Diabetic Cardiomyopathy ◽  
Nuclear Factor Κb ◽  
Diabetic Rats ◽  
Signal Pathways ◽  
Mortality And Morbidity ◽  
Beneficial Effects ◽  
Male Wistar Rats ◽  
Glucose Plasma

Diabetes-induced injury of myocardium, defined as diabetic cardiomyopathy (DCM), accounts for significant mortality and morbidity in diabetic population. Alleviation of DCM by a potent drug remains considerable interests in experimental and clinical researches because hypoglycemic drugs cannot effectively control this condition. Here, we explored the beneficial effects of isosteviol sodium (STVNa) on type 1 diabetes-induced DCM and the potential mechanisms involved. Male Wistar rats were induced to diabetes by injection of streptozotocin (STZ). One week later, diabetic rats were randomly grouped to receive STVNa (STZ/STVNa) or its vehicle (STZ). After 11 weeks of treatment or 11 weeks treatment following 4 weeks of removal of the treatment, the cardiac function and structure were evaluated and related mechanisms were investigated. In diabetic rats, oxidative stress, inflammation, blood glucose and plasma advanced glycation end products (AGEs) were significantly increased, whereas superoxide dismutase 2 (SOD-2) expression and activity were decreased. STVNa treatment inhibited cardiac hypertrophy, fibrosis and inflammation, showed similar ratio of heart to body weight and antioxidant capacities almost similar to the normal controls, which can be sustained at least 4 weeks. Moreover, STVNa inhibited diabetes-inducted stimulation of both extracellular signal-regulated kinase (ERK) and nuclear factor κB (NF-κB) signal pathways. However, blood glucose, plasma AGE and insulin levels were not altered by STVNa treatment. These results indicate that STVNa may be developed into a potent therapy for DCM. The mechanism underlying this therapeutic effect involves the suppression of oxidative stress and inflammation by inhibiting ERK and NF-κB without changing blood glucose or AGEs.

scholarly journals Identification of Energy Metabolism Changes in Diabetic Cardiomyopathy Rats Using a Metabonomic Approach

2018 ◽  
Vol 48 (3) ◽  
pp. 934-946 ◽  
Author(s):  
Liangcai Zhao ◽  
Minjian Dong ◽  
Cuicui Xu ◽  
Hong Zheng ◽  
Tingting Wei ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Drug Targets ◽  
Tca Cycle ◽  
High Energy ◽  
Diabetic Rats ◽  
Metabolic Changes ◽  
Dependent Manner ◽  
Cardiac Tissues ◽  
1H Nuclear Magnetic Resonance ◽  
Energy Synthesis

Background/Aims: Diabetic cardiomyopathy (DCM) is a serious complication of diabetes. It is therefore crucial to elucidate the characteristic metabolic changes that occur during the development of diabetes to gain an understanding the pathogenesis of this disease and identify potential drug targets involved. Methods: 1H nuclear magnetic resonance-based metabonomics combined with HPLC measurements were used to determine the metabolic changes in isolated cardiac tissues after 5 weeks, 9 weeks, and 15 weeks in rats treated with streptozotocin. Results: Pattern recognition analysis clearly discriminated the diabetic rats from time-matched control rats, suggesting that the metabolic profile of the diabetic group was markedly different from that of the controls. Quantitative analysis showed that the levels of energy metabolites, such as the high-energy phosphate pool (ATP and creatine), significantly decreased in a time-dependent manner. Correlation analysis revealed the inhibition of glycolysis and the tricarboxylic acid (TCA) cycle, enhanced lipid metabolism, and changes in some amino acids, which may have led to the decline in energy production in the DCM rats. Conclusions: The results indicated that the administration of energy substances or the manipulation of myocardial energy synthesis induced by increased glucose oxidation may contribute to the amelioration of cardiac dysfunction in diabetes.

scholarly journals Comparative Study of the Effects of GLP1 Analog and SGLT2 Inhibitor against Diabetic Cardiomyopathy in Type 2 Diabetic Rats: Possible Underlying Mechanisms

Biomedicines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 43 ◽  
Author(s):  
Abdelaziz M. Hussein ◽  
Elsayed A. Eid ◽  
Medhat Taha ◽  
Rami M. Elshazli ◽  
Raouf Fekry Bedir ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Cardiomyopathy ◽  
Caspase 3 ◽  
Sglt2 Inhibitor ◽  
Diabetic Rats ◽  
Tnf Α ◽  
Cardioprotective Effects ◽  
Underlying Mechanisms ◽  
Type 2 Diabetic

The present study investigated the possible cardioprotective effects of GLP1 and SGLT2i against diabetic cardiomyopathy (DCM) in type 2 diabetic rats and the possible underlying mechanisms. Methods: Thirty-two male Sprague Dawley rats were randomly subdivided into 4 equal groups: (a) control group, (b) DM group, type 2 diabetic rats with saline daily for 4 weeks, (c) DM + GLP1, as DM group with GLP1 analogue (liraglutide) at a dose of 75 µg/kg for 4 weeks, and (d) DM + SGLT2i as DM group with SGLT2 inhibitor (dapagliflozin) at a dose of 1 mg/kg for 4 weeks. By the end of treatment (4 weeks), serum blood glucose, homeostasis model assessment insulin resistance (HOMA-IR), insulin, and cardiac enzymes (LDH, CK-MB) were measured. Also, the cardiac histopathology, myocardial oxidative stress markers (malondialdehyde (MDA), glutathione (GSH) and CAT) and norepinephrine (NE), myocardial fibrosis, the expression of caspase-3, TGF-β, TNF-α, and tyrosine hydroxylase (TH) in myocardial tissues were measured. Results: T2DM caused significant increase in serum glucose, HOMA-IR, serum CK-MB, and LDH (p < 0.05). Also, DM caused significant myocardial damage and fibrosis; elevation of myocardial MDA; NE with upregulation of myocardial caspase-3, TNF-α, TGF-β, and TH; and significant decrease in serum insulin and myocardial GSH and CAT (p < 0.05). Administration of either GLP1 analog or SGLT2i caused a significant improvement in all studied parameters (p < 0.05). Conclusion: We concluded that both GLP1 and SGLT2i exhibited cardioprotective effects against DCM in T2DM, with the upper hand for SGLT2i. This might be due to attenuation of fibrosis, oxidative stress, apoptosis (caspase-3), sympathetic nerve activity, and inflammatory cytokines (TNF-α and TGF-β).

scholarly journals Simvastatin Ameliorates Diabetic Cardiomyopathy by Attenuating Oxidative Stress and Inflammation in Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Nawal M. Al-Rasheed ◽  
Nouf M. Al-Rasheed ◽  
Iman H. Hasan ◽  
Maha A. Al-Amin ◽  
Hanaa N. Al-Ajmi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Body Weight ◽  
Diabetic Cardiomyopathy ◽  
Troponin I ◽  
Body Weight Loss ◽  
Diabetic Rats ◽  
Antioxidant Defenses ◽  
Lipid Lowering ◽  
Diabetic Heart ◽  
Creatine Kinase Mb

Simvastatin is a lipid-lowering agent used to treat hypercholesterolemia and to reduce the risk of heart disease. This study scrutinized the beneficial effects of simvastatin on experimental diabetic cardiomyopathy (DCM), pointing to the role of hyperglycemia-induced oxidative stress and inflammation. Diabetes was induced by intraperitoneal injection of streptozotocin and both control and diabetic rats received simvastatin for 90 days. Diabetic rats showed significant cardiac hypertrophy, body weight loss, hyperglycemia, and hyperlipidemia. Serum creatine kinase MB (CK-MB) and troponin I showed a significant increase in diabetic rats. Simvastatin significantly improved body weight, attenuated hyperglycemia and hyperlipidemia, and ameliorated CK-MB and troponin I. Simvastatin prevented histological alterations and deposition of collagen in the heart of diabetic animals. Lipid peroxidation and nitric oxide were increased in the heart of diabetic rats whereas antioxidant defenses were decreased. These alterations were significantly reversed by simvastatin. In addition, simvastatin decreased serum inflammatory mediators and expression of NF-κB in the diabetic heart. Cardiac caspase-3 was increased in the diabetic heart and decreased following treatment with simvastatin. In conclusion, our results suggest that simvastatin alleviates DCM by attenuating hyperglycemia/hyperlipidemia-induced oxidative stress, inflammation, and apoptosis.

scholarly journals Comparison of Oxidant/Antioxidant, Detoxification Systems in Various Tissue Homogenates and Mitochondria of Rats with Diabetes Induced by Streptozocin

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Veysel Kenan Çelık ◽  
Zeynep Deniz Şahın ◽  
İsmail Sari ◽  
Sevtap Bakir
Keyword(s):  
Oxidative Stress ◽  
Tissue Injury ◽  
Total Antioxidant Status ◽  
Diabetic Rats ◽  
Stress Index ◽  
Control Group ◽  
Cardiac Tissues ◽  
Mitochondrial Fractions ◽  
Total Antioxidant ◽  
Tissue Homogenates

Objective. Oxidative stress is considered to be the main factor in the development of diabetic complications and tissue injury. our objective was to investigate and compare the oxidant/antioxidant conditions and detoxification mechanisms of the liver, lung, kidney, cardiac tissues, and mitochondria of rats with diabetes induced by streptozocin (STZ).Methods. Rats with diabetes induced by streptozocin were anesthetized by administering 90 mg/kg ketamine hydrochloride and 3 mg/kg xylazine hydrochloride. Thoracic cavities were incised open; liver, lung, kidney, and cardiac tissues were removed and stored at−70°C. All samples were homogenized and mitochondrial fractions were separated. Total Antioxidant Status (TAS), Total Oxidant Status (TOS), Oxidative Stress Index (OSI), Paraoxonase (PON), Arylesterase, Catalase (Cat), Malondialdehyde (MDA), and Glutathion-S-transferase were measured in each fraction.Results. MDA and TOS levels were significantly increased in liver tissues, and T OS and OSI were increased in the mitochondrial fractions of diabetic rats. These increases were not statistically significant compared to the control group. No significant differences were determined in the antioxidant and GST activities.Conclusion. According to our results, oxidative stress has not developed in rats with diabetes induced by streptozocin. The detoxification system was induced; however, this induction did not differ significantly from the controls.

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