scholarly journals Ganglion cells apoptosis in diabetic rats as early prediction of glaucoma: a study of Brn3b gene expression and association with change of quantity of NO, caspase-3, NF-κB, and TNF-α

2020 ◽  
Vol 13 (12) ◽  
pp. 1872-1879
Author(s):  
Irwan Tjandra ◽  
Widya Artini ◽  
Nurjati Chairani Siregar ◽  
Andi Arus Victor
Keyword(s):  
Gene Expression ◽  
Caspase 3 ◽  
Ganglion Cells ◽  
Open Angle Glaucoma ◽  
Rna Extraction ◽  
Diabetic Rats ◽  
Control Group ◽  
Sprague Dawley ◽  
Tnf Α

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.

Mirabegron, A Selective β3-Adrenoceptor Agonist Causes an Improvement in Erectile Dysfunction in Diabetic Rats

2019 ◽  
Author(s):  
Didem Yilmaz-Oral ◽  
Ecem Kaya-Sezginer ◽  
Dilan Askin ◽  
Yesim Hamurtekin ◽  
Serap Gur
Keyword(s):  
Erectile Dysfunction ◽  
Pde5 Inhibitor ◽  
Corpus Cavernosum ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Control Group ◽  
Sprague Dawley ◽  
Intracavernosal Injection ◽  
Relaxation Responses

Abstract Aim To investigate the possible beneficial effect of mirabegron [a selective β3-adrenoceptor (AR) agonist] treatment on erectile dysfunction (ED) in streptozotocin-induced diabetic rats. Methods Sprague-Dawley rats (n=20) were divided into two groups: control group and streptozotocin-induced diabetic group. In vivo erectile responses were evaluated after intracavernosal injection of mirabegron (0.4 mg/kg) in rats. The relaxation responses to electrical field stimulation (EFS, 10 Hz), sodium nitroprusside (SNP, 10 nM) and sildenafil (1 μM) of corpus cavernosum (CC) strips were examined after the incubation with mirabegron (10 μM). β3-ARs expression and localization were determined by Western blot and immunohistochemical analyses in CC tissue. Results In vivo erectile responses of diabetic rats [intracavernasal pressure (ICP) / mean arterial pressure, 0.17±0.01] were decreased, which were restored after administration of mirabegron (0.75±0.01, P<0.001). The basal ICP (7.1±0.6 mmHg) in diabetic rats was markedly increased after mirabegron (36.1 ±5.4 mmHg, P<0.01). Mirabegron caused markedly relaxation in diabetic rat CC after phenylephrine precontraction. The relaxation responses to EFS and sildenafil were reduced in diabetic CC, which were increased in the presence of mirabegron. Mirabegron enhanced SNP-induced relaxation response in both groups. The expression and immunoreactivity of β3-ARs localized to CC smooth muscle were observed in control and diabetic rats. Conclusions This is the first study to show that intracavernosal administration of mirabegron improved erectile function and neurogenic relaxation of CC in diabetic rats. These results may be supported by further studies using combinations of mirabegron and phosphodiesterase type 5 (PDE5) inhibitors for the treatment of diabetic ED, especially in patients who do not respond to PDE5 inhibitor therapy.

scholarly journals Features of a necrotic and inflammatory process in different forms of nonalcoholic fatty liver disease

2017 ◽  
Vol 89 (2) ◽  
pp. 52-58 ◽  
Author(s):  
I V Kurbatova ◽  
O P Dudanova
Keyword(s):  
Gene Expression ◽  
Liver Disease ◽  
Fatty Liver ◽  
Proinflammatory Cytokines ◽  
Fatty Liver Disease ◽  
Inflammatory Process ◽  
Caspase 3 ◽  
Control Group ◽  
Nonalcoholic Fatty Liver ◽  
Tnf Α

Aim. To identify the features of development of a necrotic and inflammatory process in different forms of nonalcoholic fatty liver disease (NAFLD), by comparatively analyzing a full set of clinical and laboratory parameters, including the cytokine status and the expression level of enzyme genes controlling the apoptosis of peripheral leukocytes. Subjects and methods 86 patients with NAFLD, including 8 (9.3%) with hepatic steatosis (HS), 70 (81.4%) with nonalcoholic steatohepatitis (NASH), 40, 19, and 11 with mild, moderate, and high disease activity, respectively, and 8 (9.3%) with liver cirrhosis (LC), were examined. A control group consisted of 34 healthy donors. Clinical and biochemical blood indices, cytokine profile, and the level of caspase gene transcripts in the peripheral blood leukocytes (PBL) were estimated. Results. As compared to the controls, the patients with HS had higher tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) levels and lower caspase 3, 6, and 8 mRNA in PBL. The concentration of IL-10 in NASH was higher than that in steatosis and positively correlated with the level of proinflammatory cytokines. The levels of TNF-α and IL6 were higher in the patients with NASH than in the controls. Those of C-reactive protein, γ-globulin, IL-6, and cytokeratin-18 fragment increased with the progression of NASH. In the latter, the transcriptional activity of caspase-3 gene decreased relative to the reference value and negatively correlated with the level of proinflammatory cytokines. In the patients with LC, the gene expression profile of caspases in PBL was similar to that in the control group; the level of IL-6 was higher than that in steatosis and NASH, that of IL-1β was higher than in HS and positively correlated the concentration of IL-6 and the activity of alanine aminotransferase and aspartate aminotransferase. Conclusion. The features of a necrotic and inflammatory process were identified in different forms of NAFLD. When the latter progressed, the cytokine profile and gene expression levels of caspases in PBL altered along with a change in the general clinical picture.

An aqueous extract fromMoringa oleiferaleaves ameliorates hepatotoxicity in alloxan-induced diabetic rats

2017 ◽  
Vol 95 (4) ◽  
pp. 524-530 ◽  
Author(s):  
Mabrouk Attia Abd Eldaim ◽  
Ahmed Shaban Abd Elrasoul ◽  
Samy Ahmed Abd Elaziz
Keyword(s):  
Gene Expression ◽  
Lipid Peroxidation ◽  
Aqueous Extract ◽  
Caspase 3 ◽  
Diabetic Rats ◽  
Control Group ◽  
Albino Rats ◽  
Hepatic Lipid ◽  
The Third ◽  
Hepatic Lipid Peroxidation

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.

scholarly journals Investigation of an antidiabetic potential of a phenolic compound isolated from the leaves of mempelas paya

2016 ◽  
Vol 15 (1) ◽  
Author(s):  
Qamar Uddin Ahmed ◽  
Siti Zaiton Mat Soad ◽  
Mehnaz Afrin ◽  
Wan Mohd. Azizi Wan Sulaiman
Keyword(s):  
Phenolic Compound ◽  
Diabetes Management ◽  
Diabetic Control ◽  
Diabetic Rats ◽  
Control Group ◽  
Active Principle ◽  
Sprague Dawley ◽  
Toxicological Evaluation ◽  
Toxicological Studies

Introduction: Leaves of mempelas paya (Tetracera indica) (family: Dilleniaceae) is traditionally used in diabetes management in Malaysia. However, no attempt has ever been made to discover an active principle responsible for its blood glucose lowering effect. Hence, this research deals with the isolation, in vivo antidiabetic and toxicological evaluation of an active principle. Methods: Chemical investigation of methanol extract derived from the powdered leaves resulted in the isolation of a phenolic compound through repeated silica gel column chromatography. The structure was elucidated by spectroscopic (1H-NMR, 13C-NMR, MS, IR and UV) analysis. In vivo antidiabetic and toxicological studies were carried out using Sprague-Dawley rats (diabetic and normal) at three different concentrations (1, 5 and 25 mg/kg b.w.). Results: 5,7-dihydroxy-8methoxyflavone was found to exhibit significant anti-hyperglycaemic activity (p<0.05) in diabetic rats at 5 and 25 mg/kg b.w. without showing hypoglycaemic effect in normal rats. The anti-hyperglycaemic activity was found to be comparable with glibenclamide (GLBC) (p<0.05). In vivo toxicological study for continuous 21 days showed no abnormal activity and mortality. Histopathology of kidney, liver and pancreas of both normal and diabetic treated rats demonstrated normal and improved condition when compared to diabetic control group. There were no significant changes seen in the kidney (serum urea and creatinine) and lipid (TC, TG, LDL-C and HDL-C) functional parameters tested. Conclusions: 5,7-dihydroxy-8-methoxyflavone isolated from the leaves of mempelas paya coud be a safe antidiabetic agent.

scholarly journals CHRONIC EXPERIMENTAL DIABETES MELLITUS

2015 ◽  
Vol 22 (12) ◽  
pp. 1560-1564
Author(s):  
Mohammad Afzal Khan ◽  
Faris Mohammed Nour Altaf ◽  
Muhammad Naeem Chaudhry
Keyword(s):  
Dorsal Root ◽  
Experimental Diabetes ◽  
Ganglion Cells ◽  
Diabetic Rats ◽  
Human Anatomy ◽  
Control Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Metabolic Requirement ◽  
Dorsal Root Ganglion Cells

Background: Multiple factors operate in the development of diabetic neuropathy.Sensory neurons are not protected by blood-brain or blood-nerve barrier; also the dorsal rootganglion cells (DRG) have a higher metabolic requirement than the nerve trunks. Oxygen levelat the dorsal root ganglions also appears to be lower. All these physiological characteristicssuggest that DRG may be particularly susceptible to damage in prolonged diabetic conditions.Objectives: To observe the quantitative cellular changes in dorsal root ganglion cells in rats withprolonged experimental diabetes. Study Design: An experimental study. Setting: Departmentof Human Anatomy, Faculty of Medicine, Umm al Qura University, Makkah, Saudi Arabia.Period: Fifteen months to complete. Material and methods: Observations were made on sixcontrol and six streptozotocin-treated male Sprague-Dawley rats after 12 months of diabetes.Cell count was done on silver-stained paraffin sections. DRG cells were arbitrarily groupedas large A-type and small B-type. Statistical examination of the cell count was done using atwo-tailed t-test. Values were considered significant at P ≤ 0.05. Results: In the control groupof animals the mean total number was 15856.33 ± 552.538 while in the diabetic animals itwas 11836.666 ±583.177; the reduction in the number of cells was significant. The number ofA-type and B-type cells and their percentages in the control group and the diabetic group ofanimals were 2753.833±257.683 (17.36%), 13102.5±443.092 (82.63%) and 1202.833±87.082(10.16%), 10633.833±517.900 (89.83%) respectively. The differences in the number of A-typeand B-type of cells when compared between control and diabetic groups of animals werestatistically highly significant. Conclusion: Selective cells damage to DRG cells may be theharbinger of diabetic neuropathy in experimentally induced diabetic rats.

scholarly journals Comparative gene expression analysis of Fas and related genes in Comparative gene expression analysis of Fas and related genes in preeclamptic and healthy women: A cross-sectional study

2020 ◽  
Author(s):  
Zaima Ali ◽  
Saba Khaliq ◽  
Saima Zaki ◽  
Hafiz Usman Ahmad ◽  
Khalid Pervaiz Lone
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Mononuclear Cells ◽  
Rna Extraction ◽  
Control Group ◽  
Hypertensive Disorder ◽  
Cross Sectional ◽  
Tnf Α

Background: Preeclampsia is a hypertensive disorder of pregnancy affecting about 2-10% pregnancies worldwide. mRNA expression of tumor necrosis factor alpha (TNF-α), Fas, and FasL have been reported to be altered in placental bed in preeclamptic pregnancies. We hypothesized that the expression of these genes is also altered in peripheral blood mononuclear cells (PBMCs) in preeclampsia. Objective: To compare the expression of Fas receptor and related genes in PBMCs of preeclamptic and normotensive pregnant women. Materials and Methods: A cross-sectional comparative study comprising of 18 cases and 18 controls was designed. 5 ml of venous blood was drawn and collected considering aseptic measures. Buffy coat was separated by centrifugation and stored at –20°C. Favor Prep total RNA Isolation Kit (Favorgen, Taiwan) was used for RNA extraction. The mRNA expression of TNF-α, Fas, and FasL was measured by real-time polymerase chain reaction in PBMCs in preeclamptic and normal pregnancies. Results: A significant increase in mRNA expression of TNF-α, Fas, and FasL (p ≤ 0.001) was observed in PBMCs of preeclamptic pregnancies compared to the control group (p ≤ 0.001). Moreover, a significant positive correlation was found between the TNF-α mRNA expression and Fas and FasL (p ≤ 0.001). Conclusion: The results lead to the conclusion that mRNA expression of TNF-α, Fas, and FasL in the maternal PBMCs is altered in preeclamptic pregnancies and might contribute to the pathogenesis of the disease. Key words: Preeclampsia, TNF-α, Fas, Apoptosis.

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
Keyword(s):  
Gene Expression ◽  
Wistar Rats ◽  
Caspase 3 ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Control Group ◽  
Rt Pcr ◽  
Hippocampal Region ◽  
Protein Levels ◽  
Family Gene

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.

Facilitated migration of cells from a transected peripheral nerve over collagen fibers: in vivo observations

1989 ◽  
Vol 47 ◽  
pp. 888-889
Author(s):  
Arthur J. Wasserman ◽  
Azam Rizvi ◽  
George Zazanis ◽  
Frederick H. Silver
Keyword(s):  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Collagen Gel ◽  
Collagen Fibers ◽  
Control Group ◽  
Guide Tube ◽  
Sprague Dawley ◽  
Silicone Tube ◽  
Thin Sections

In cases of peripheral nerve damage the gap between proximal and distal stumps can be closed by suturing the ends together, using a nerve graft, or by nerve tubulization. Suturing allows regeneration but does not prevent formation of painful neuromas which adhere to adjacent tissues. Autografts are not reported to be as good as tubulization and require a second surgical site with additional risks and complications. Tubulization involves implanting a nerve guide tube that will provide a stable environment for axon proliferation while simultaneously preventing formation of fibrous scar tissue. Supplementing tubes with a collagen gel or collagen plus extracellular matrix factors is reported to increase axon proliferation when compared to controls. But there is no information regarding the use of collagen fibers to guide nerve cell migration through a tube. This communication reports ultrastructural observations on rat sciatic nerve regeneration through a silicone nerve stent containing crosslinked collagen fibers.Collagen fibers were prepared as described previously. The fibers were threaded through a silicone tube to form a central plug. One cm segments of sciatic nerve were excised from Sprague Dawley rats. A control group of rats received a silicone tube implant without collagen while an experimental group received the silicone tube containing a collagen fiber plug. At 4 and 6 weeks postoperatively, the implants were removed and fixed in 2.5% glutaraldehyde buffered by 0.1 M cacodylate containing 1.5 mM CaCl2 and balanced by 0.1 M sucrose. The explants were post-fixed in 1% OSO4, block stained in 1% uranyl acetate, dehydrated and embedded in Epon. Axons were counted on montages prepared at a total magnification of 1700x. Montages were viewed through a dissecting microscope. Thin sections were sampled from the proximal, middle and distal regions of regenerating sciatic plugs.

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 Modulatory Effects of Osthole on Lipopolysaccharides-Induced Inflammation in Caco-2 Cell Monolayer and Co-Cultures with THP-1 and THP-1-Derived Macrophages

Nutrients ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 123
Author(s):  
Natalia K. Kordulewska ◽  
Justyna Topa ◽  
Małgorzata Tańska ◽  
Anna Cieślińska ◽  
Ewa Fiedorowicz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Inflammatory Reaction ◽  
Wide Spectrum ◽  
Cell Monolayer ◽  
In Vivo Studies ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Tnf Α

Lipopolysaccharydes (LPS) are responsible for the intestinal inflammatory reaction, as they may disrupt tight junctions and induce cytokines (CKs) secretion. Osthole has a wide spectrum of pharmacological effects, thus its anti-inflammatory potential in the LPS-treated Caco-2 cell line as well as in Caco-2/THP-1 and Caco-2/macrophages co-cultures was investigated. In brief, Caco-2 cells and co-cultures were incubated with LPS to induce an inflammatory reaction, after which osthole (150–450 ng/mL) was applied to reduce this effect. After 24 h, the level of secreted CKs and changes in gene expression were examined. LPS significantly increased the levels of IL-1β, -6, -8, and TNF-α, while osthole reduced this effect in a concentration-dependent manner, with the most significant decrease when a 450 ng/mL dose was applied (p < 0.0001). A similar trend was observed in changes in gene expression, with the significant osthole efficiency at a concentration of 450 ng/μL for IL1R1 and COX-2 (p < 0.01) and 300 ng/μL for NF-κB (p < 0.001). Osthole increased Caco-2 monolayer permeability, thus if it would ever be considered as a potential drug for minimizing intestinal inflammatory symptoms, its safety should be confirmed in extended in vitro and in vivo studies.

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