scholarly journals Dapagliflozin Attenuates Diabetic Cardiomyopathy Through Erythropoietin Up-Regulation of AKT/JAK/MAPK Pathways in Streptozotocin-Induced Diabetic Rats

2021 ◽  
Author(s):  
Nora El-Sayed ◽  
Yasser M. Mostafa ◽  
Noha M AboGresha ◽  
Amal A.M. Ahmed ◽  
Islam Z. Mahmoud ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Diabetic Rats ◽  
Cardiac Cells ◽  
Control Group ◽  
Histological Structure ◽  
Dependent Manner ◽  
Functional Changes ◽  
Mapk Cascades ◽  
Group 2 ◽  
Histopathological Studies

Abstract Purpose: This study was designed to investigate the mechanism of Dapagliflozin (Dapa) cardioprotection against diabetic cardiomyopathy (DCM). Structural and functional changes in the heart as well as decrease of Erythropoietin (EPO) levels were reported in DCM. EPO simultaneously activates three pathways: the Janus-activated kinase–signal transducer and activator of transcription (JAK2/STAT5), phosphatidylinositol-3-kinase-Akt (PI3K/Akt), and extracellular signal-related kinase (ERK/MAPK) cascades, that result in proliferation and differentiation of cardiac cells.Methods and Results: DCM was induced by a high fat diet for 10 weeks followed by administration of streptozotocin. After confirmation of diabetes, rats were divided randomly to 5 groups: Group 1; normal control group, Group 2; untreated diabetic group and Groups (3-5); diabetic groups received Dapa daily (0.75 mg, 1.5 or 3 mg /Kg, p.o) respectively for a month. At the end of the experiment, full anaesthesia was induced in all rats using ether inhalation and ECG was recorded. Blood samples were collected then rats were sacrificed and their heart were dissected out and processed for biochemical and histopathological studies. Untreated diabetic rats showed abnormal ECG pattern, elevation of serum cardiac enzymes, decrease EPO levels, downregulation of P-Akt, P-JAK2 and pMAPK pathways, abnormal histological structure of the heart and increase immunostaining intensity of P53 and TNF α in the cardiomyocytes. Dapa in a dose dependent manner attenuated the alterations in the previously mentioned parameters. Conclusion: The cardioprotective effect of Dapa could be mediated by increasing EPO levels and activation of P-Akt, P-JAK2 and pMAPK signalling cascades which in turn decrease apoptosis.

scholarly journals Hirudo Lyophilized Powder Ameliorates Renal Injury in Diabetic Rats by Suppressing Oxidative Stress and Inflammation

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Fan Yang ◽  
Yachun Li ◽  
Shuai Guo ◽  
Yongmei Pan ◽  
Cuihuan Yan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Treatment Group ◽  
Microvascular Complications ◽  
Renal Tissue ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Control Group ◽  
Functional Changes ◽  
Diabetic Model ◽  
Group 2

As diabetic nephropathy (DN) is one of the most common and destructive microvascular complications of diabetes mellitus, the goal of this study, therefore, was to investigate the renal protective effect and latent mechanisms of Hirudo lyophilized powder on diabetic rats. In this study, all rats were randomly assigned into the control group and diabetic group. The rats of diabetic group were injected with low-dose STZ (35 mg/kg) intraperitoneal plus high-fat diet to induce diabetes. Then, the successful diabetic model rats were weighed and randomly assigned into four groups: (1) diabetic model group (DM group); (2) Hirudo lyophilized powder 0.3 g/kg treatment group (SL group); (3) Hirudo lyophilized powder 0.6 g/kg treatment group (SM group); (4) Hirudo lyophilized powder 1.2 g/kg treatment group (SH group). Their fasting blood glucoses (FBG) were measured every 4 weeks. After treatment with Hirudo lyophilized powder at a corresponding dose once a day for 16 weeks, their metabolic and biochemical as well as oxidative stress parameters were tested, and the kidney weight (KW)/body weight (BW) was calculated. The renal tissues were used for histological, mRNA, and protein expression analysis. The results showed that Hirudo lyophilized powder could protect against the structural damages and functional changes of diabetic renal tissue by inhibiting oxidative stress, inflammation, and fibrosis. Furthermore, it was found in the further research that inhibiting the NOX4 expression and JAK2/STAT1/STAT3 pathway activation might be the underlying mechanisms. Collectively, Hirudo lyophilized powder might be a promising therapeutic agent for the treatment of DN.

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 Atorvastatin impairs liver mitochondrial function in obese Göttingen Minipigs but heart and skeletal muscle are not affected

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Liselotte Bruun Christiansen ◽  
Tine Lovsø Dohlmann ◽  
Trine Pagh Ludvigsen ◽  
Ewa Parfieniuk ◽  
Michal Ciborowski ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Function ◽  
Citrate Synthase ◽  
Obese Group ◽  
Control Group ◽  
Dependent Manner ◽  
Respiratory Capacity ◽  
Protein Carbonyl Content ◽  
Functional Changes ◽  
Mitochondrial Respiratory

AbstractStatins lower the risk of cardiovascular events but have been associated with mitochondrial functional changes in a tissue-dependent manner. We investigated tissue-specific modifications of mitochondrial function in liver, heart and skeletal muscle mediated by chronic statin therapy in a Göttingen Minipig model. We hypothesized that statins enhance the mitochondrial function in heart but impair skeletal muscle and liver mitochondria. Mitochondrial respiratory capacities, citrate synthase activity, coenzyme Q10 concentrations and protein carbonyl content (PCC) were analyzed in samples of liver, heart and skeletal muscle from three groups of Göttingen Minipigs: a lean control group (CON, n = 6), an obese group (HFD, n = 7) and an obese group treated with atorvastatin for 28 weeks (HFD + ATO, n = 7). Atorvastatin concentrations were analyzed in each of the three tissues and in plasma from the Göttingen Minipigs. In treated minipigs, atorvastatin was detected in the liver and in plasma. A significant reduction in complex I + II-supported mitochondrial respiratory capacity was seen in liver of HFD + ATO compared to HFD (P = 0.022). Opposite directed but insignificant modifications of mitochondrial respiratory capacity were seen in heart versus skeletal muscle in HFD + ATO compared to the HFD group. In heart muscle, the HFD + ATO had significantly higher PCC compared to the HFD group (P = 0.0323). In the HFD group relative to CON, liver mitochondrial respiration decreased whereas in skeletal muscle, respiration increased but these changes were insignificant when normalizing for mitochondrial content. Oral atorvastatin treatment in Göttingen Minipigs is associated with a reduced mitochondrial respiratory capacity in the liver that may be linked to increased content of atorvastatin in this organ.

scholarly journals Growth Performance, Histological Structure of Duodenum and Pectoralis Muscle of Kampung Chickens After Administration of Antibiotic Growth Promoter

2018 ◽  
Vol 42 (2) ◽  
Author(s):  
Hendry Trisakti Saragih ◽  
Suci Aulia Ratu Fajrin ◽  
Sovia Nur Janah ◽  
Ria Oktafianti ◽  
Elgio Venanda Ginting ◽  
...  
Keyword(s):  
Growth Performance ◽  
Muscle Performance ◽  
Control Group ◽  
Histological Structure ◽  
Growth Promoter ◽  
Pectoralis Muscle ◽  
Visceral Organ ◽  
Group 3 ◽  
Group 2 ◽  
One Way Anova

This study aimed to know the effect of AGP on growth performance, duodenal histological structure and pectoralis muscle of Kampung chicken. This research was conducted by designing 3 groups with each group consisting of 20-day old chicks (DOC) of Kampung chickens. The control group was given basal feed without AGP bacitracin, group 2 was treated with 0.125 g of bacitracin /kg of basal feed and group 3 was treated with 0.25 g bacitracin/kg of basal feed until 12 days old. The parameters observed were chicken body weight on days posthatch, 3, 5, 7, 9, and 12, morphometry, visceral organ weight, duodenal organ morphology and muscle performance of Pectoralis thoracicus at 12 days old. Data analysis used one way ANOVA test followed by Tukey test with significance of P≤ 0,05. The result showed that the morphology of the doudenum and the myofiber area of group 3 indicated significant differences compared to the control group. The conclusion of this study revealed that administration of AGP bacitracin with 0.25 g/ kg dose of basal feed may increase the growth performance of Kampung chicken.

scholarly journals Evaluation of Kidney Function Parameters in Diabetic Rats Following Virgin Coconut Oil Diet

Folia Medica ◽  
2019 ◽  
Vol 61 (2) ◽  
pp. 249-257 ◽  
Author(s):  
Akinjide M. Akinnuga ◽  
Olubayode Bamidele ◽  
Anthony J. Adewumi
Keyword(s):  
Kidney Function ◽  
Biochemical Analysis ◽  
Coconut Oil ◽  
Diabetic Rats ◽  
Control Group ◽  
Virgin Coconut Oil ◽  
Normal Rat ◽  
Group 2 ◽  
Diabetes Control Group ◽  
Group 1

Abstract Background: Diabetes mellitus (DM) leads to disruption of kidney function parameters (KFPs) which are markers of kidney diseases, especially nephropathy. Virgin coconut oil (VCO) has been implicated in playing a significant role in DM management. However, its role on KFPs in DM is scarce. Aim: To evaluate the kidney function parameters following VCO diet in diabetic rats. Materials and methods: : Twenty-five (25) male rats of 150 – 200 g were divided into 5 groups (n=5): Non-diabetic control (Group 1), diabetes control (Group 2), diabetes + metformin (Group 3), diabetes + 10% VCO (Group 4) and diabetes + 20% VCO (Group 5). Apart from Group 1, other groups were given intraperitone-ally 50 mg/kg of streptozotocin to induce diabetes mellitus. After 72 hours, fasting hyperglycaemia was confirmed by glucose oxidase method. All the rats were fed normal rat chow for 8 weeks. At 8th week, serum and urine samples were analysed for biochemical analysis. After 8 weeks, Group 1 and Group 2 continued to be fed on normal rat chow while other groups were treated with diets (VCO) or drug (metformin) for 4 weeks. At 12th week, urine samples were collected for biochemical analysis, the rats were sacrificed, and blood samples were collected by cardiac puncture. Results: There were significant differences in some KFPs in diabetes control (Group 2) compared to other experimental groups. However, there was no significant difference in glomerular filtration rate (GFR) and serum sodium in all the groups. Conclusion: VCO supplementary diet improved the altered KFPs and could be a therapy for kidney problems.

EFFECT OF DIPYRIDAMOLE + ASA ON THE RETINE VASCULAR PATTERN OF ESTREPTOZOTOCIN-DIABETIC RATS

1987 ◽  
Author(s):  
A Moreno ◽  
J P de la Cruz ◽  
J Garcia Campos ◽  
F Sanchez de la Cuesta
Keyword(s):  
Treated Group ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Male Rats ◽  
Control Group ◽  
Vascular Pattern ◽  
Vascular Tree ◽  
Aorta Ring ◽  
Vascular Bed ◽  
Group 2

INTRODUCTIONWe have used an experimental model which allows the evaluation of the qualitative differences in the retinal vascular pattern by means of the labeling of the retine vascular tree with radish peroxidase (HRP) in estreptozotocin-diabetic rats. The aim of the study was to evaluate the effect of ASA and DIP + ASA on the vessels platelet behaviour of said retine pattern in a group of rats in t-hich the diabetes had 3 months of evolution.PROCEDURE22 Wistar male rats were divided into A groups; 1) control group, 2) diabetic rats without antiaggregant, 3) dietetic rats treated with 6 mg/day ASA p.o., 4) diabetic rats treated with 6 mg/day ASA +12 mg/day DIP p.o. For inducing diabetes 30 mg/Kg of i.v. estreptozotocine were administered. The animals were considered “diabetic” when glucemia was over 200 mg/100 ml. After 3 months of treatment with 4IU insuline and ASA, or ASA + DIP, the animals were sacrified. Samples of blood and rings of descending aorta were extracted. Platelet aggregation in IJB in front of 1 μg/ml of collagen and the prostacycline-like activity of the aorta ring were evaluated. The configuration of the retine vascular tree labeled with HRP was observed.RESULTS AND CONCLUSIONSMaximal aggregation intensity: 11.1 Ω in the control group,10.9Ω in the diabetic non-treated group, 4.8Ω in rats receiving ASA and 4.6Ω in rats treated with DIP + ASA. The incUbation during 10 min. of aorta rings in blood samples produced 38.7% inhibition in the control group, 12.8% in the non treated-diabetic group 0% in the ASA group and 49.3% in the group treated with DIP + ASA.The qualitative changes in the diabetic rats retinal vascular network non treated with antiaggregants showed a scarce visibility of capillars as well as large zones of tortuous vessels. The rats treated with ASA showed a continuous vascular bed and less tortuous vessels than the ones in the non treated group but the vascular diameters were smaller than the ones observed in non-diabetic rats; the rats treated with DIP + ASA showed a continuous vascular bed, scarce tortuous vessels and vascular diameters similar to the ones found in non-diabetic rats. Mortality rates: 0% in the control group, 50% in the non-treated diabetic group, 16% in the ASA group and 0% in the DIP + ASA group. The administration of DIP + ASA normalized the prostacycline-like activity and the retinal vascular pattern in estreptozotocin-diabetic rats.

Injection mixed drug intratumoral to produce ROS and creating a coagulum as cancer therapeutics drug depot.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15635-e15635
Author(s):  
Jian Zhang ◽  
Qiang Fu ◽  
Bian Li ◽  
Yan Han ◽  
Dong Chen ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Tumor Imaging ◽  
Cancer Therapeutics ◽  
Water Soluble ◽  
Control Group ◽  
Histological Structure ◽  
High Concentration ◽  
Long Time ◽  
Group 2 ◽  
Scanning Imaging

e15635 Background: To explore the nature of hydrogen peroxide at higher dosage for denature-aggregation of tumor with drugs through aggregation in denatured tumor as a coagulum for drug depot and prolong function of drug. Methods: (1). Preparation for two 5 ml of BLM-I131, one diluted with 0.12 ml NS and 0.2 ml (0.2mCi = 49.67µg BLM) for tumor injection in control group; one diluted with 0.12 ml of H2O2 (0.833 mg/ml) and 0.2 ml (0.2mCi = 49.67µg BLM) for tumor injection in experimental group. (2).Tumor imaging with BLM-I131 analyzed at different time points. (3). Radioactivity in tumor of mice analyzed under SPECT scanning imaging instrument at the 0, 5 h, 1 h, 2 h, 4 h, 8 h, 24 h, 48 h, 96 h, 120 h, 144 h and 168 h, activity of isotope I131 is representing the BLM retaining time in tumor. (4). Also, tumor sectioned and observed cellular and extracellular matrix changes of histological structure. Results: It was observed that BLM-I131 with ROS in tumors sustained for 168 hours while BLM-I131 with NS in tumors sustained for 8 hours only. Radioactivity of BLM-I131 in tumors with ROS reach at peak 1.5 hours and second peak at 20 hours by average to extend to 168 hours, while radioactivity of BLM-I131 in tumors with NS reached at peak in 0.5 hour, decreased to 30% in 1.5 hour quickly to background in 8 hours; We observed the extracellular matrix changes in experimental tumor while no changes in control tumor. Conclusions: A water soluble oxidant mixed with free drug can play a biological scissors role to chop tumor matrix, then it resulted in a denature tumor matrix into a coagulation for a drug depot, it showed drug of BLM-I131 sustained in tumor for a long time; while oxidant plays an important role to punch holes on cell membrane and resulted a high permeability for high concentration drug in each cancer cells.

scholarly journals A Comparison of Wound Healing Rate Following Treatment with Aftamed and Chlorine Dioxide Gels in Streptozotocin-Induced Diabetic Rats

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Fouad Al-Bayaty ◽  
Mahmood Ameen Abdulla
Keyword(s):  
Wound Healing ◽  
Chlorine Dioxide ◽  
Cellular Proliferation ◽  
Radical Scavenging ◽  
Diabetic Control ◽  
Diabetic Rats ◽  
Control Group ◽  
Sprague Dawley ◽  
Thickness Skin ◽  
Group 2

Background and Purpose. This study aimed to evaluate the wound healing activities of Aftamed and chlorine dioxide gels in streptozotocin-induced diabetic rats. Experimental Approach. Forty-eight Sprague Dawley rats were chosen for this study, divided into 4 groups. Diabetes was induced. Two-centimeter-diameter full-thickness skin excision wounds were created. Animals were topically treated twice daily. Groups 1, the diabetic control group, were treated with 0.2 mL of sterile distilled water. Group 2 served as a reference standard were treated with 0.2 mL of Intrasite gel. Groups 3 and 4 were treated with 0.2 mL of Aftamed and 0.2 mL of chlorine dioxide gels respectively. Granulation tissue was excised on the 10th day and processed for histological and biochemical analysis. The glutathione peroxidase ,superoxide dismutase activities and the malondialdehyde (MDA) levels were determined. Results. Aftamed-treated wounds exhibited significant increases in hydroxyproline, cellular proliferation, the number of blood vessels, and the level of collagen synthesis. Aftamed induced an increase in the free radical-scavenging enzyme activity and significantly reduced the lipid peroxidation levels in the wounds as measured by the reduction in the MDA level. Conclusions. This study showed that Aftamed gel is able to significantly accelerate the process of wound healing in diabetic rats.

scholarly journals The Protective Effect of Marigold Hydroalcoholic Extract in STZ-Induced Diabetic Rats: Evaluation of Cardiac and Pancreatic Biomarkers in the Serum

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Esmaeel Ebrahimi ◽  
Saeed Shirali ◽  
Rahman Talaei
Keyword(s):  
Diabetes Mellitus ◽  
Protective Effect ◽  
Antioxidant Property ◽  
Diabetic Control ◽  
Diabetic Rats ◽  
Control Group ◽  
Dependent Manner ◽  
Hydroalcoholic Extract ◽  
Diabetic Control Group ◽  
Male Wistar Rats

Diabetes mellitus is the most common endocrine disorder worldwide and it is usually along with complications such as retinopathy, neuropathy, nephropathy, and cardiovascular disease. The prevalence of diabetes is increasing and its treatment has created concerns in society. The use of herbal medicine can be helpful in the management of diabetes mellitus. The aim of this study was to investigate the protective effect of marigold hydroalcoholic extract under diabetes condition. A total of 36 male Wistar rats were randomly divided into four groups: normal control group, diabetic control group, and groups treated with 250 or 500 mg/kg hydroalcoholic extract of marigold flower during four weeks. At the end of the study, the rats were anesthetized with ketamine/xylazine, and sampling was performed through cardiac puncture. The results showed that treatment with marigold improved body weight. In addition, we determined that marigold normalized the level of CK-MB, total CK, amylase, and lipase in a dose-dependent manner. Probably these effects resulted from antioxidant property of marigold; thus we suggest that marigold flower can be useful for reduction of diabetes complication.

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.

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