scholarly journals Evaluation of Bcl-2 Family Gene Expression and Caspase-3 Activity in Hippocampus STZ-Induced Diabetic Rats

2008 ◽  
Vol 2008 ◽  
pp. 1-6 ◽  
Author(s):  
Iraj Jafari Anarkooli ◽  
Mojtaba Sankian ◽  
Shahriar Ahmadpour ◽  
Abdol-ReZa Varasteh ◽  
Hossein Haghir

We assessed the expression of Bcl-2 family members at both mRNA and protein levels as well as the Caspase-3 activity, in order to investigate the occurrence of apoptosis in hippocampus of STZ-induced diabetic rats. We selected twenty-four Wistar rats; half of them were made diabetic by intraperitoneal injection of a single 60 mg/kg dose of streptozotocin (STZ, IP), while the others received normal saline and served as controls. The expressions of Bcl-2,Bcl-xL, and Bax mRNA and proteins were measured using RT-PCR and western blotting, respectively. Caspases-3 activity was determined by using the Caspase-3/CPP32 Fluorometric Assay Kit. The result showed that mRNA and protein levels of Bcl-2 andBcl-xLwere lower in hippocampus of diabetic group than that of the control group, whereas expressions of Bax in hippocampus of diabetic rats were higher than that of controls at both mRNA and protein levels (P<.01). Hyperglycemia was found to raise 6.9-fold hippocampal caspase-3 activity in diabetic group compared with control group (P<.001). Therefore, the induction of diabetes is associated with increased ratios of Bax/Bcl-2, Bax/Bcl-xL, and increased caspase-3 activity in hippocampus which shows that apoptosis is favored in hippocampal region.

2017 ◽  
Vol 95 (4) ◽  
pp. 524-530 ◽  
Author(s):  
Mabrouk Attia Abd Eldaim ◽  
Ahmed Shaban Abd Elrasoul ◽  
Samy Ahmed Abd Elaziz

This study was carried out to evaluate the possible mechanisms through which an aqueous extract from MO leaves demonstrates hepatoprotective effects in alloxan-induced diabetic rats. Eighty albino rats were assigned to 4 groups. The control group was orally administered sterile saline. The second group was injected with alloxan (150 mg/kg body mass (b.m.)) by intraperitoneal injection (i.p.). The third group was given MO (250 mg/kg b.m.) orally, daily. The fourth group was injected with alloxan, as for the second group, and administrated an aqueous extract of MO leaves, as for the third group. Alloxan induced degenerative changes in hepatic and pancreatic tissues, increased hepatic lipid peroxidation, and increased gene expression of PC and caspase 3. However, it decreased the activities of hepatic SOD and CAT, and gene expression of GS. In contrast, the MO extract prevented changes to the histoarchitecture of hepatic and pancreatic tissues and normalized the reduced hepatic levels of glutathione, as well as the activities of SOD and CAT, and the gene expression of GS, while reducing blood glucose levels, hepatic lipid peroxidation, and the gene expression of PC and caspase 3. This study indicated that an aqueous extract of MO leaves can be a potent antioxidant and used as an hepatoprotective agent.


2001 ◽  
Vol 11 (6) ◽  
pp. 609-613 ◽  
Author(s):  
Honório S. Menezes ◽  
Marinez Barra ◽  
André R. Belló ◽  
Cristiano B. Martins ◽  
Paulo Zielinsky

Introduction: The frequent occurrence of prenatal hypertrophy of the muscular ventricular septum has been widely reported in fetuses of diabetic mothers. Objectives: This experimental study was carried out to test the hypothesis that the weight of the heart, the ratio of the cardiac weight to that of the body, the thickness of the muscular ventricular septum, and the myocytic profile within the ventricular septum are all increased in fetuses of diabetic rats in comparison to fetuses of normal rats. Methods: Diabetes was induced in 5 pregnant Wistar rats, bearing 30 fetuses, on the eighth day after conception, by intraperitoneal injection of 50mg/kg of streptozotocin. Five normal pregnant Wistar rats, bearing 20 fetuses, made up the control group. Morphometric data were obtained by a computer-assisted method applied to the measurements of the thickness of the ventricular septum, and myocytic nuclear area. Statistical analysis utilized Student's t-test and Kruskal-Wallis test. Results: The mean thickness of the septum was 675.56 μm (± 159) in the control fetuses, and 904.39 μm (± 262) in the fetuses carried by diabetic mothers (p < 0.001). The cardiac weight was 0.016 g (± 0.004) in the control group, and 0.023 g (± 0.005) in the group of diabetic fetuses (p < 0.001). The ratio of cardiac to body weight was 0.294% (± 0.079) in the control group, and 0.514% (± 0.073) in the diabetic group (p < 0.001). The myocytic nuclear area was 14.70 μm2 in the control group, and 21.43 μm2 in the diabetic group (p < 0.001). Conclusions: The presence of cellular and morphologic cardiac hypertrophy in fetuses of diabetic rats was demonstrated by the significant difference between the two groups for each analyzed feature.


2020 ◽  
Vol 15 (4) ◽  
pp. 396-403
Author(s):  
Mansoor Shahriari ◽  
Saeed Mehrzadi ◽  
Masood Naseripour ◽  
Iman Fatemi ◽  
Azam Hosseinzadeh ◽  
...  

Objective: The present study was designed to evaluate the effects of Atorvastatin (ATO) plus Melatonin (MEL) on streptozocin-induced Diabetic Retinopathy (DR) in rats. Methods: Diabetes was induced in Wistar rats with an intraperitoneal injection of streptozocin (50 mg/kg). Animals were randomly assigned to one of the following groups (8 rats/group): Control group, Diabetic group, Diabetic + MEL group (20 mg/kg/day), Diabetic + ATO group (10 mg/kg/day), Diabetic + MEL + ATO group (as above). Treatments were started one week after induction of diabetes and continued for 7 weeks. At the end of the experiment, angiography was performed and the rats were killed and retinas were harvested for pathological and molecular examinations. Results: Administration of MEL reduced the fluorescein leakage, MDA and ROS levels compared to diabetic group. Treatment with ATO only reduced ROS levels compared to diabetic group. In addition, administration of ATO plus MEL decreased these indices compared to the diabetic and ATO groups. Histologically, retinal vascular congestion was not observed in the combined ATO and MEL group as compared to the diabetic, ATO, and MEL groups. Conclusion: These data provide evidence for the therapeutic value of MEL in combination with ATO in clinical practice for prevention of DR.


2020 ◽  
Vol 13 (12) ◽  
pp. 1872-1879
Author(s):  
Irwan Tjandra ◽  
Widya Artini ◽  
Nurjati Chairani Siregar ◽  
Andi Arus Victor

AIM: To find a new concept to show whether or not apoptosis of retinal ganglion cells (RGCs) can be determined in the histology of acute hyperglycemia in the role of expressed Brn3b gene related to nitric oxide (NO), caspase-3, nuclear factor kappa-B (NF-κB), and tumor necrosis factor-α (TNF-α) as an early predictor of primary open angle glaucoma (POAG) eyes and their associations. METHODS: Experimental in vivo study was carried out using adult male, white Sprague-Dawley rats aged ≥2mo, weighing 150-200 g. The animals were divided into two groups, one group receiving intraperitoneal injection of streptozotociz 50 mg/kg in 0.01 mol/L citric buffer and pH 4.5 and a comparison made with the control group. Retinal tissue was divided into two parts (both experimental and control groups respectively): a) right retina for immunohistochemistry (IHC; caspase-3 and TNF-α); b) left retina was divided into two parts for the purpose of real-time polymerase chain reaction (PCR) test (RNA extraction for Brn3b gene expression analysis) and ELISA test (NO and NF-κB). RESULTS: The experimental group showed a decrease in Brn3b gene expression compared to the control group (1.3-fold lower in 2nd month; 1.1-fold lower in 4th month and 2.5-fold lower in 6th month). However, there was a decrease of NO, caspase-3, and an increase of NF-κB and TNF-α quantity. CONCLUSION: The expression of mRNA Brn3b gene is inversely proportional to apoptosis in RGCs. The quantity of NO, caspase-3, NF-κB and TNF-α is influential in expression of Brn3b in RGCs caused by hyperglycemia in diabetic rats.


2020 ◽  
Vol 20 (7) ◽  
pp. 1117-1132
Author(s):  
Abdelaziz M. Hussein ◽  
Elsayed A. Eid ◽  
Ismaeel Bin-Jaliah ◽  
Medhat Taha ◽  
Lashin S. Lashin

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.


2009 ◽  
Vol 24 (4) ◽  
pp. 251-255 ◽  
Author(s):  
Honório Sampaio Menezes ◽  
Cláudio Galeano Zettler ◽  
Alice Calone ◽  
Jackson Borges Corrêa ◽  
Carla Bartuscheck ◽  
...  

PURPOSE: To compare body weight and length, heart weight and length, heart-to-body weight ratio, glycemia, and morphometric cellular data of offspring of diabetic rats (ODR) and of normal rats (control). METHODS: Diabetes was induced in 3 pregnant Wistar rats, bearing 30 rats, on the 11th day after conception by intraperitoneal injection of 50 mg/kg of streptozotocin. Six normal pregnant Wistar rats, bearing 50 rats, made up the control group. Morphometric data were obtained using a scale for the weight, length, heart and body measurements. Morphometric cellular data were obtained by a computer assisted method applied to the measurements of myocytes. Statistical analysis utilized Student's t-test, ANOVA and Levene test. RESULTS: Control offspring had greater mean body weight and length than offspring of diabetic rats (p < 0.001). Heart weight and length and heart-to-body ratios of newborn rats differed between groups at birth (p < 0.001), but showed no difference at 21 days. Mean nuclei area and perimetric value of the myocytes decrees throughout the first 21 days of life (p < 0.01) in the diabetic group. CONCLUSIONS: Heart hypertrophy on the offspring of diabetic rats at birth was demonstrated by the significant difference between the groups. After the eleventh day, no difference was found, which confirmed regression of cardiomegaly. The significant difference between the first and the 21th day of life, for nuclei area feature, demonstrate regression of cardiac hypertrophy in the offspring of diabetic rats.


2017 ◽  
Vol 75 (1) ◽  
pp. 30-35 ◽  
Author(s):  
Cristiane Iozzi Silva ◽  
Paulo Cézar Novais ◽  
Andressa Romualdo Rodrigues ◽  
Camila A.M. Carvalho ◽  
Benedicto Oscar Colli ◽  
...  

ABSTRACT Alcohol consumption aggravates injuries caused by ischemia. Many molecular mechanisms are involved in the pathophysiology of cerebral ischemia, including neurotransmitter expression, which is regulated by microRNAs. Objective: To evaluate the microRNA-219 and NMDA expression in brain tissue and blood of animals subjected to cerebral ischemia associated with alcoholism. Methods: Fifty Wistar rats were divided into groups: control, sham, ischemic, alcoholic, and ischemic plus alcoholic. The expression of microRNA-219 and NMDA were analyzed by real-time PCR. Results: When compared to the control group, the microRNA-219 in brain tissue was less expressed in the ischemic, alcoholic, and ischemic plus alcoholic groups. In the blood, this microRNA had lower expression in alcoholic and ischemic plus alcoholic groups. In the brain tissue the NMDA gene expression was greater in the ischemic, alcoholic, and ischemic plus alcoholic groups. Conclusion: A possible modulation of NMDA by microRNA-219 was observed with an inverse correlation between them.


2019 ◽  
Vol 4 (4) ◽  
pp. 137-142
Author(s):  
Vahid Azizi ◽  
Shahrbanoo Oryan ◽  
Homayuon Khazali ◽  
Abdolkarim Hosseini

Introduction: The neuropeptide Y (NPY) in the neural circuits of the hypothalamus has a stimulating effect on reproductive activities in mammals. Kisspeptin (KiSS1) is a quintessential neurotransmitter in the reproductive axis which directly stimulates gonadotropin-releasing hormone neurons in the hypothalamus. The distribution of KiSS1 expressing cells in the pituitary was described previously. Despite earlier reports showing the KiSS1 receptor, G-protein coupled receptor 54 (GPR54) expression in the pituitary, the potential physiological roles of kisspeptin at this gland have remained obscure. Accordingly, this study investigated the role of NPY on the relative expression of Kiss1 and Gpr54 genes in the pituitary gland in male Wistar rats. Methods: In general, 20 male Wistar rats weighing 200-250 g in 4 groups (5 in each group) received saline, NPY (2.3 nM), BIBP3226 (NPY receptor antagonist, 7.8 nM), and NPY+ BIBP3226. Then, they received the simultaneous injection of these molecules through the third ventricle of the brain. Finally, the relative mean expressions of Kiss1 and Gpr54 genes in the anterior pituitary were quantitatively analyzed by the real-time polymerase chain reaction. Results: The central injection of NPY increased the relative mean expressions of Kiss1 and Gpr54 genes in the pituitary gland compared to the control group although the injection of BIBP3226 eradicated these effects. However, the gene expression of Gpr54 in the rats receiving NPY coupled with BIBP3226 in hypophysis in comparison to the group receiving only NPY demonstrated a significant reduction (P<0.05). Conclusion: Overall, the central injection of NPY stimulated the gene expression of Kiss1 and Gpr54 in the pituitary gland.


Author(s):  
Abbas Bakhteyari ◽  
Yasaman Zarrin ◽  
Parvaneh Nikpour ◽  
Zeinab Sadat Hosseiny ◽  
Zeinab Sadat Hosseiny ◽  
...  

Background: Diabetes mellitus deeply changes the genes expression of integrin (Itg) subunits in several cells and tissues such as monocytes, arterial endothelium, kidney glomerular cells, retina. Furthermore, hyperglycemia could impress and reduce the rate of successful assisted as well as non-assisted pregnancy. Endometrium undergoes thorough changes in normal menstrual cycle and the question is: What happens in the endometrium under diabetic condition? Objective: The aim of the current study was to investigate the endometrial gene expression of α3, α4, αv, Itg β1 and β3 subunits in diabetic rat models at the time of embryo implantation. Materials and Methods: Twenty-eight rats were randomly divided into 4 groups: control group, diabetic group, pioglitazone-treated group, and metformin-treated group. Real-time PCR was performed to determine changes in the expression of Itg α3, α4, αv, β1, and β3 genes in rat’s endometrium. Results: The expression of all Itg subunits increased significantly in diabetic rats’ endometrium compared with control group. Treatment with pioglitazone significantly reduced the level of Itg subunits gene expression compared with diabetic rats. While metformin had a different effect on α3 and α4 and elevated these two subunits gene expression. Conclusion: Diabetes mellitus significantly increased the expression of studied Itg subunits, therefore untreated diabetes could be potentially assumed as one of the preliminary elements in embryo implantation failure.


2018 ◽  
Vol 8 (1) ◽  
pp. 6-6 ◽  
Author(s):  
Parisa Jamor ◽  
Hassan Ahmadvand ◽  
Hesam Ashoory ◽  
Esmaeel Babaeenezhad

Background: Myeloperoxidase (MPO) is involved in the initiation, progression, and complications of atherosclerosis in diabetic patients. Objectives: In the current study, the impact of alpha-lipoic acid (LA), a natural antioxidant and a cofactor in the enzyme complexes on MPO, catalase (CAT) and glutathione peroxidase (GPx) activity, glutathione (GSH) and malondialdehyde (MDA) level, histopathology of kidney and expression of antioxidant enzymes, superoxide dismutase (SOD), GPx and CAT which are involved in the detoxification of reactive oxygen species (ROS), was evaluated in alloxan-induced diabetic rats. Materials and Methods: In this study, 30 male Rattus norvegicus rats randomly divided into three groups; control (C), non-treated diabetic (NTD), and LA-treated diabetics (LATD) was induced by alloxan monohydrate (100mg/kg; subcutaneous [SC]). Then treatment was performed with alphaLA (100 mg/kg intraperitoneal (i.p) daily to 6 weeks). Blood sample of animals collected to measure levels of MPO, CAT and GPx activity GSH and MDA. Kidney paraffin sections were prepared to estimate histological studies and to measure quantitative gene expression SOD, GPX and CAT in kidney. Results: Induction of diabetes led to a significant increase in MPO and MDA, reduced GSH level and GPx and CAT activities (P < 0.05). However, treatment with alpha-LA led to a significant elevation in GPx, CAT and GSH levels with a reduction in MPO activities and MDA levels (P < 0.05). Furthermore, the real-time reverse transcriptase-polymerase chain reaction (RT-PCR) analysis results showed increased expressions of GPx, CAT and SOD enzyme in the treatment group compared with the diabetic control group. Histopathological lesions such as increased glomerular volume and lymphocyte infiltration were attenuated in the alpha-LA treated group. Conclusions: Our findings indicated that alpha-LA supplementation is effective in preventing complications induced by oxidative stress and atherosclerosis in diabetic rats.


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