Streptozotocin-induced diabetic cardiomyopathy in rats: ameliorative effect of PIPERINE via Bcl2, Bax/Bcl2, and caspase-3 pathways

2020 ◽  
Vol 84 (12) ◽  
pp. 2533-2544 ◽  
Author(s):  
Yan Wang ◽  
Hui Sun ◽  
Jianwu Zhang ◽  
Zhiyang Xia ◽  
Wei Chen
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Caspase 3 ◽  
Ameliorative Effect

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.

Ameliorative effect of Gongronema latifolium leaf extract on alloxan-induced diabetic cardiomyopathy in Wistar rats model

2020 ◽  
Vol 29 (4) ◽  
pp. 865-872
Author(s):  
Mary Abiola Okesola ◽  
Oluwafemi Adeleke Ojo ◽  
Sunday Amos Onikanni ◽  
Basiru Olaitan Ajiboye ◽  
Babatunji Emmanuel Oyinloye ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Wistar Rats ◽  
Leaf Extract ◽  
Ameliorative Effect ◽  
Gongronema Latifolium

Ameliorative effect ofAegle marmelosleaf extract on early stage alloxan-induced diabetic cardiomyopathy in rats

2011 ◽  
Vol 49 (11) ◽  
pp. 1137-1143 ◽  
Author(s):  
Rajbir Bhatti ◽  
Shikha Sharma ◽  
Jatinder Singh ◽  
Mohan Paul S. Ishar
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Early Stage ◽  
Ameliorative Effect

scholarly journals Diabetes induces and calcium channel blockers prevent cardiac expression of proapoptotic thioredoxin-interacting protein

2009 ◽  
Vol 296 (5) ◽  
pp. E1133-E1139 ◽  
Author(s):  
Junqin Chen ◽  
Hyunjoo Cha-Molstad ◽  
Anna Szabo ◽  
Anath Shalev
Keyword(s):  
Calcium Channel ◽  
Diabetic Cardiomyopathy ◽  
Calcium Channel Blockers ◽  
Caspase 3 ◽  
Critical Role ◽  
Cardiomyocyte Apoptosis ◽  
Channel Blockers ◽  
Dependent Manner ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein

Cardiomyocyte apoptosis is a critical process in the pathogenesis of ischemic and diabetic cardiomyopathy, but the mechanisms are not fully understood. Thioredoxin-interacting protein (TXNIP) has recently been shown to have deleterious effects in the cardiovascular system and we therefore investigated whether it may also play a role in diabetes-associated cardiomyocyte apoptosis. In fact, TXNIP expression was increased in H9C2 cardiomyocytes incubated at high glucose, and cardiac expression of TXNIP and cleaved caspase-3 were also elevated in vivo in streptozotocin- and obesity-induced diabetic mice. Together, these findings not only suggest that TXNIP is involved in diabetic cardiomyopathy but also that it may represent a novel therapeutic target. Surprisingly, testing putative TXNIP modulators revealed that calcium channel blockers reduce cardiomyocyte TXNIP transcription and protein levels in a dose-dependent manner. Oral administration of verapamil for 3 wk also reduced cardiac TXNIP expression in mice even in the face of severe diabetes, and these reduced TXNIP levels were associated with decreased apoptosis. To determine whether lack of TXNIP can mimic the verapamil-induced decrease in apoptosis, we used TXNIP-deficient HcB-19 mice, harboring a natural nonsense mutation in the TXNIP gene. Interestingly, we found significantly reduced cleaved caspase-3 levels in HcB-19 hearts, suggesting that TXNIP plays a critical role in cardiac apoptosis and that the verapamil effects were mediated by TXNIP reduction. Thus our results suggest that TXNIP reduction is a powerful target to enhance cardiomyocyte survival and that agents such as calcium channel blockers may be useful in trying to achieve this goal and prevent diabetic cardiomyopathy.

scholarly journals Apoptosis of cardiomyocytes in diabetic cardiomyopathy involves overexpression of glycogen synthase kinase-3β

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Wei Wu ◽  
Xingxing Liu ◽  
Longfei Han
Keyword(s):  
Mrna Expression ◽  
Diabetic Cardiomyopathy ◽  
Myocardial Injury ◽  
Caspase 3 ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Control Group ◽  
Glycogen Synthase Kinase 3Β ◽  
Rat Cardiomyocytes ◽  
Gsk 3Β

Abstract To evaluate the role of glycogen synthase kinase-3β (GSK-3β) in the apoptosis of cardiomyocytes in diabetic cardiomyopathy (DCM). Diabetes mellitus (DM) in rats was induced by intraperitoneal injection of 1% streptozotocin (STZ), and lithium chloride (LiCl) was used to decrease the expression of GSK-3β. Hematoxylin/eosin (HE) staining and the terminal deoxyribonucleotide transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay was conducted to evaluate the pathological injury and apoptosis of cardiomyocytes respectively. Western blot was applied to detect the protein expressions of Cleaved-caspase 3, caspase 3, Bax and Bcl-2 in rat cardiomyocytes. Real-time polymerase chain reaction (RT-PCR) was applied to detect the gene expressions of phosphoinositide 3-kinases (PI3K), Akt, and GSK-3β in rat cardiomyocytes. DM-induced cardiomyocyte injuries, which were presented as capillary basement membrane thickening, interstitial fibrosis, cardiomyocyte hypertrophy and necrosis in HE staining and increased apoptosis detected by TUNEL assay. When comparing with the control group, the mRNA expression of PI3K and Akt in DM group obviously decreased but the mRNA expression of GSK-3β obviously elevated (P < 0.05). In addition, the ratio of Cleaved-caspase 3/caspase 3 and Bax/Bcl-2 were notably increased in DM group compared with control group (P < 0.05). LiCl, as an inhibitor of GSK-3 apparently reduced the expression of GSK-3β mRNA (P < 0.05) but not the PI3K and Akt comparing with the DM group. LiCl also attenuated the myocardial injury and apoptosis induced by DM. The myocardial injury induced by DM is associated with the up-regulation of GSK-3β. LiCl inhibited the expression of GSK-3β and myocardial apoptosis in diabetic myocardium.

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).

Curcumin attenuates palmitic acid-induced cell apoptosis by inhibiting endoplasmic reticulum stress in H9C2 cardiomyocytes

2019 ◽  
Vol 38 (6) ◽  
pp. 655-664 ◽  
Author(s):  
G Guan ◽  
L Lei ◽  
Q Lv ◽  
Y Gong ◽  
L Yang
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Expression ◽  
Cell Viability ◽  
Palmitic Acid ◽  
Er Stress ◽  
Diabetic Cardiomyopathy ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Protective Action ◽  
H9c2 Cardiomyocytes

Diabetic cardiomyopathy is mediated by multiple molecular mechanisms including endoplasmic reticulum (ER) stress. Curcumin, a phenolic compound, has cytoprotective properties, but its potential protective action against diabetic cardiomyopathy and the related molecular mechanisms are not fully elucidated. In this study, we evaluated the effects of curcumin on cell viability and apoptosis in palmitic acid (PA)-treated H9C2 cardiomyocytes and investigated the signaling pathways involved. Treatment with PA reduced cell viability, induced apoptosis, enhanced apoptosis-related protein expression (Caspase 3 and BCL-2 associated X protein (BAX)), and activated ER stress marker protein expression (glucose-regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP)). Curcumin attenuated PA-induced reduction in cell viability and activation of apoptosis, Caspase 3 activity, BAX, CHOP, and GRP78 expression. 4-Phenylbutyric acid (4-PBA) attenuated the PA-induced effects on cell viability and apoptosis, similar to curcumin. Both curcumin and 4-PBA also attenuated PA-induced increase in ER stress protein (CHOP and GRP78) expression. Curcumin also protected against cytotoxicity, apoptosis, and ER stress induced by thapsigargin. These findings indicate that PA triggers apoptosis in H9C2 cells via ER stress pathways and curcumin protects against this phenomenon.

scholarly journals Effect of Astragalus Polysaccharides on Cardiac Dysfunction in db/db Mice with Respect to Oxidant Stress

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Wei Chen ◽  
Qilin Sun ◽  
Jing Ju ◽  
Wenjie Chen ◽  
Xuelan Zhao ◽  
...  
Keyword(s):  
Protein Expression ◽  
P38 Mapk ◽  
Diabetic Cardiomyopathy ◽  
Caspase 3 ◽  
Target Genes ◽  
Oxidant Stress ◽  
Diabetic Mice ◽  
Astragalus Polysaccharides ◽  
Ultra Structure ◽  
Ros Formation

Objective. Oxidant stress plays an important role in the development of diabetic cardiomyopathy. Previously we reported that Astragalus polysaccharides (APS) rescued heart dysfunction and cardinal pathological abnormalities in diabetic mice. In the current study, we determined whether the effect of APS on diabetic cardiomyopathy was associated with its impact on oxidant stress. Methods. Db/db diabetic mice were employed and administered with APS. The hematodynamics, cardiac ultra-structure, apoptosis, and ROS formation of myocardium were assessed. The cardiac protein expression of apoptosis target genes (Bax, Bcl-2, and caspase-3) and oxidation target genes (Gpx, SOD2, t/p-JNK, catalase, t/p-p38 MAPK, and t/p-ERK) were evaluated, respectively. Results. APS therapy improved hematodynamics and cardinal ultra-structure with reduced apoptosis and ROS formation in db/db hearts. In addition, APS therapy inhibited the protein expression of apoptosis target genes (Bax, Bcl-2, and caspase-3) and regulated the protein expression of oxidation target genes (enhancing Gpx, SOD2, and catalase, while reducing t/p-JNK, t/p-ERK, and t/p-p38 MAPK) in db/db hearts. Conclusion. Our findings suggest that APS has benefits in diabetic cardiomyopathy, which may be partly associated with its impact on cardiac oxidant stress.

Ameliorative Effect of Flavonoid-rich Extracts from Gongronema latifolium Against Diabetic Cardiomyopathy via serpin A3 and socs3-a in Streptozocin Treated Rats

Biomarkers ◽  
2021 ◽  
pp. 1-28
Author(s):  
Babatunji Emmanuel Oyinloye ◽  
B. O. Ajiboye ◽  
Oluwafolakemi Johnson ◽  
Olutunmise Victoria Owolabi ◽  
Jerius Nkwuda Ejeje ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Ameliorative Effect ◽  
Gongronema Latifolium
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