Poly herbal formulation ameliorates diabetic cardiomyopathy through attenuation of cardiac inflammation and oxidative stress via NF-κB/Nrf-2/HO-1 pathway in diabetic rats

Background: Diabetic cardiomyopathy (DCM) is characterized by cardiac fibrosis and stiffness, which often develops into heart failure. This study investigated the role of Ras protein-specific guanine nucleotide releasing factor 1 (RasGRF1) in the development of DCM. Methods: Forty-eight mice were divided into four groups (n = 12 per group): Group 1: Wild-type (WT) mice, Group 2: RasGRF1 deficiency (RasGRF1−/−) mice. Group 3: Streptozotocin (STZ)-induced diabetic WT mice, Group 4: STZ-induced diabetic RasGRF1−/− mice. Myocardial functions were assessed by cardiac echography. Heart tissues from all of the mice were investigated for cardiac fibrosis, inflammation, and oxidative stress markers. Results: Worse impaired diastolic function with elevation serum interleukin (IL)-6 was found in the diabetic group compared with the non-diabetic groups. Serum IL-6 levels were found to be elevated in the diabetic compared with the non-diabetic groups. However, the diabetic RasGRF1−/− mice exhibited lower serum IL-6 levels and better diastolic function than the diabetic WT mice. The diabetic RasGRF1−/− mice were associated with reduced cardiac inflammation, which was shown by lower invading inflammation cells, lower expression of matrix metalloproteinase 9, and less chemokines compared to the diabetic WT mice. Furthermore, less oxidative stress as well as extracellular matrix deposition leading to a reduction in cardiac fibrosis was also found in the diabetic RasGRF1−/− mice compared with the diabetic WT mice. Conclusion: The deletion of RasGRF1 attenuated myocardial fibrosis and improved cardiac function in diabetic mice through inhibiting inflammation and oxidative stress.

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

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/1871530320666200420084444 ◽

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.

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Protective role of Sterculia tragacantha aqueous extract on pancreatic gene expression and oxidative stress parameters in streptozotocin-induced diabetic rats

Journal of Complementary and Integrative Medicine ◽

10.1515/jcim-2021-0020 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Basiru Olaitan Ajiboye ◽

Babatunji Emmanuel Oyinloye ◽

Jennifer Chidera Awurum ◽

Sunday Amos Onikanni ◽

Adedotun Adefolalu ◽

...

Keyword(s):

Oxidative Stress ◽

Body Weight ◽

Protective Role ◽

Diabetic Rats ◽

Gene Expressions ◽

Ki 67 ◽

Oxidative Stress Parameters ◽

And Oxidative Stress ◽

Stress Parameters

Abstract Objectives The current study evaluates the protective role of aqueous extract of Sterculia tragacantha leaf (AESTL) on pancreatic gene expressions (insulin, PCNA, PDX-1, KI-67 and GLP-1R) and oxidative stress parameters in streptozotocin-induced diabetic rats. Methods Diabetes mellitus was induced into the experimental Wistar animals via intraperitoneal (IP) injection of streptozotocin (35 mg/kg body weight) and 5% glucose water was given to the rats for 24 h after induction. The animals were categorized into five groups of 10 rats each as follows normal control, diabetic control, diabetic rats administered AESTL (150 and 300 mg/kg body weight) and diabetic rats administered metformin (200 mg/kg) orally for two weeks. Thereafter, the animals were euthanized, blood sample collected, pancreas harvested and some pancreatic gene expressions (such as insulin, PCNA, PDX-1, KI-67, and GLP-1R)s as well as oxidative stress parameters were analyzed. Results The results revealed that AESTL significantly (p<0.05) reduced fasting blood glucose level, food and water intake, and lipid peroxidation in diabetic rats. Diabetic rats administered different doses of AESTL showed a substantial upsurge in body weight, antioxidant enzyme activities, and pancreatic gene expressions (insulin, PCNA, PDX-1, KI-67, and GLP-1R). Conclusions It can therefore be concluded that AESTL has the ability to protect the pancreas during diabetes mellitus conditions.

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Beneficial Effect of Aqueous Garlic Extract on Inflammation and Oxidative Stress Status in the Kidneys of Type 1 Diabetic Rats

Indian Journal of Clinical Biochemistry ◽

10.1007/s12291-016-0621-6 ◽

2016 ◽

Vol 32 (3) ◽

pp. 329-336 ◽

Cited By ~ 12

Author(s):

Abolfazl Nasiri ◽

Nasrin Ziamajidi ◽

Roghayeh Abbasalipourkabir ◽

Mohammad Taghi Goodarzi ◽

Massoud Saidijam ◽

...

Keyword(s):

Oxidative Stress ◽

Beneficial Effect ◽

Diabetic Rats ◽

Garlic Extract ◽

Oxidative Stress Status ◽

And Oxidative Stress

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Mitigating effects of antioxidant properties of Artemisia campestris leaf extract on hyperlipidemia, advanced glycation end products and oxidative stress in alloxan-induced diabetic rats

Food and Chemical Toxicology ◽

10.1016/j.fct.2010.05.005 ◽

2010 ◽

Vol 48 (7) ◽

pp. 1986-1993 ◽

Cited By ~ 48

Author(s):

Mediha Sefi ◽

Hamadi Fetoui ◽

Mohamed Makni ◽

Najiba Zeghal

Keyword(s):

Oxidative Stress ◽

Advanced Glycation End Products ◽

Leaf Extract ◽

Antioxidant Properties ◽

Diabetic Rats ◽

Advanced Glycation ◽

Glycation End Products ◽

End Products ◽

Artemisia Campestris ◽

And Oxidative Stress

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Lutein Dietary Supplementation Attenuates Streptozotocin-induced testicular damage and oxidative stress in diabetic rats

BMC Complementary and Alternative Medicine ◽

10.1186/s12906-015-0693-5 ◽

2015 ◽

Vol 15 (1) ◽

Cited By ~ 26

Author(s):

Amal J. Fatani ◽

Salim S. Al-Rejaie ◽

Hatem M. Abuohashish ◽

Abdullah Al-Assaf ◽

Mihir Y. Parmar ◽

...

Keyword(s):

Oxidative Stress ◽

Dietary Supplementation ◽

Diabetic Rats ◽

Testicular Damage ◽

And Oxidative Stress

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Reduction of doxorubicin-induced cytotoxicity and mitochondrial damage by betanin in rat isolated cardiomyocytes and mitochondria

Human & Experimental Toxicology ◽

10.1177/09603271211022800 ◽

2021 ◽

pp. 096032712110228

Author(s):

AA Hafez ◽

Z Jamali ◽

S Samiei ◽

S Khezri ◽

A Salimi

Keyword(s):

Oxidative Stress ◽

Protective Effect ◽

Bioactive Compound ◽

Isolated Cardiomyocytes ◽

Cardiac Inflammation ◽

Flow Cytometric ◽

Significant Toxicity ◽

Ros Formation ◽

Gene Regulatory ◽

And Oxidative Stress

Doxorubicin (DOX) is an anticancer drug which is used for treatment of several types of cancers. But the clinical use of doxorubicin is limited because of its cardiotoxicity and cardiomyopathy. Mitochondrial-dependent oxidative stress and cardiac inflammation appear to be involved in doxorubicin-induced cardiotoxicity. Betanin as a bioactive compound in Beetroot ( Beta vulgaris L.) displays anti-radical, antioxidant gene regulatory and cardioprotective activities. In this current study, we investigated the protective effect of betanin on doxorubicin-induced cytotoxicity and mitochondrial-dependent oxidative stress in isolated cardiomyocytes and mitochondria. Isolated cardiomyocytes and mitochondria were treated with three concentrations of betanin (1, 5 and 10 µM) and doxorubicin (3.5 µM) for 6 h. The parameters of cellular and mitochondrial toxicity were analyzed using biochemical and flow cytometric methods. Our results showed a significant toxicity in isolated cardiomyocytes and mitochondria in presence of doxorubicin which was related to reactive oxygen species (ROS) formation, increase in malondialdehyde (MDA), increase in oxidation of GSH to GSSG, lysosomal/mitochondrial damages and mitochondrial swelling. While betanin pretreatment reverted doxorubicin-induced cytotoxicity and oxidative stress in isolated cardiomyocytes and mitochondria. These results suggest that betanin elicited a typical protective effect on doxorubicin-induced cytotoxicity and oxidative stress. It is possible that betanin could be used as a useful adjuvant in combination with doxorubicin chemotherapy for reduction of cardiotoxicity and cardiomyopathy.

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