scholarly journals Hydrochloride pioglitazone protects diabetic rats against podocyte injury through preserving glomerular podocalyxin expression

2014 ◽  
Vol 58 (6) ◽  
pp. 630-639 ◽  
Author(s):  
Yan Xing ◽  
Shandong Ye ◽  
Yumi Chen ◽  
Wen Hu ◽  
Yan Chen
Keyword(s):  
Normal Control ◽  
Kidney Injury ◽  
Diabetic Rats ◽  
Control Group ◽  
Sprague Dawley ◽  
Urinary Sediment ◽  
Injury Index ◽  
Sprague Dawley Rats ◽  
Dose Dependent

Objective: We sought to test the effect of different dosages of pioglitazone (PIO) on the glomerular expression of podocalyxin and urinary sediment podocalyxin excretion and to explore the potential renoprotective mechanism. Materials and methods: Type 1 diabetes induced with streptozotocin (65 mg/kg) in 36 male Sprague-Dawley rats were randomly allocated to be treated with vehicle or 10, 20, 30 mg/kg/d PIO respectively for 8 weeks. Eight rats were enrolled in the normal control group. Results: At 8th week, rats were sacrificed for the observation of kidney injury through electron microscope. Glomerular podocalyxin production including mRNA and protein were determined by RT-PCR and immunohistochemistry respectively. Levels of urinary albumin excretion and urinary sediment podocalyxin, kidney injury index were all significantly increased, whereas expression of glomerular podocalyxin protein and mRNA were decreased significantly in diabetic rats compared to normal control. Dosages-dependent analysis revealed that protective effect of PIO ameliorated the physiopathological changes and reached a peak at dosage of 20 mg/kg/d. Conclusion: PIO could alleviate diabetic kidney injury in a dose-dependent pattern and the role may be associated with restraining urinary sediment podocalyxin excretion and preserving the glomerular podocalyxin expression.

A pan-NADPH Oxidase Inhibitor Ameliorates Kidney Injury in Type 1 Diabetic Rats

Pharmacology ◽  
2018 ◽  
Vol 102 (3-4) ◽  
pp. 180-189 ◽  
Author(s):  
Debra Dorotea ◽  
Guideock Kwon ◽  
Jung Hwa Lee ◽  
Erika Saunders ◽  
Yun Soo Bae ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Kidney Injury ◽  
Diabetic Rats ◽  
Oxidase Inhibitor ◽  
Dependent Manner ◽  
Diabetic Mice ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Dose Dependent

Background: NADPH oxidases (Nox) is a major enzyme system contributing to oxidative stress, which plays an important role in the pathogenesis of diabetic kidney disease (DKD). We have shown an elevation of renal Nox1, Nox2, and Nox4 in diabetic mice. APX-115, a pan-Nox inhibitor, attenuated the progression of DKD in mice. As the standard diabetic mice cannot fully mimic human DKD, the present study was aimed to show the dose-dependent effect and to provide a confirmatory evidence of APX-115 in attenuating DKD in diabetic rats. Method: Type 1 diabetes was induced by a single 60 mg/kg intraperitoneal injection of streptozotocin in Sprague-Dawley rats. 0.5, 5, or 30 mg APX-115/kg/day or losartan 1 mg/kg/day were administered orally to diabetic rats for 8 weeks. Results: APX-115 treatment showed an improvement in kidney function and tubular and podocyte ­injury, as well as attenuation of inflammation, fibrosis, and oxidative stress as much as losartan, a comparative drug and mainstay treatment in DKD. Therapeutic effect of APX-115 was exhibited in a dose-dependent manner; a dose of 30 mg/kg displayed a superior efficacy. Conclusion: This finding verified the pre-clinical data of APX-115 in protecting against DKD, which is important to bring APX-115 toward the next stage of drug development.

Electroacupuncture at Zusanli Rescues the Enteric Neuronal Loss in the Stomach of Diabetic Rats

2012 ◽  
Vol 18 (1) ◽  
pp. 5-14 ◽  
Author(s):  
Min Hu ◽  
Fan Du ◽  
Shi Liu
Keyword(s):  
High Frequency ◽  
Low Frequency ◽  
Neuronal Loss ◽  
Diabetic Rats ◽  
Enteric Neurons ◽  
Control Group ◽  
Sprague Dawley ◽  
Long Duration ◽  
Sprague Dawley Rats ◽  
Zusanli Acupoint

The purpose of this study was to investigate the effects of electroacupuncture at Zusanli acupoint on the enteric neuropathy in diabetic rats. Sprague–Dawley rats were divided into different groups depending on the total electroacupuncture span and frequency. The expression of nitric oxide synthase (nNOS), choline acetyltransferase (CHAT), protein gene product 9.5 (PGP9.5), and doublecortin was significantly decreased in the diabetic group compared with the control group. Long-term electroacupuncture at Zusanli with either high frequency or low frequency could increase the expression levels of nNOS, CHAT, PGP9.5, and doublecortin, and the increase was greater in the high-frequency group. But no obvious changes were seen in the short-term electroacupuncture groups. These results suggest that electroacupuncture at Zusanli can restore the deficiency of enteric neurons in diabetes partly but a comparative long duration of stimuli (6 weeks) is required. The increase of doublecortin may be involved in this positive process.

scholarly journals Enteral Baicalin, a Flavone Glycoside, Reduces Indicators of Cardiac Surgery-Associated Acute Kidney Injury in Rats

2018 ◽  
Vol 9 (1) ◽  
pp. 31-40 ◽  
Author(s):  
Jing Shi ◽  
Guofeng Wu ◽  
Xiaohua Zou ◽  
Ke Jiang
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Cardiac Surgery ◽  
Kidney Injury ◽  
Renal Tissue ◽  
Myeloperoxidase Activity ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Injury Index ◽  
Sprague Dawley Rats

Background/Aims: Cardiac surgery-associated acute kidney injury (CSA-AKI) is one of the most common postoperative complications in intensive care medicine. Baicalin has been shown to have anti-inflammatory and antioxidant roles in various disorders. We aimed to test the protective effects of baicalin on CSA-AKI using a rat model. Methods: Sprague-Dawley rats underwent 75 min of cardiopulmonary bypass (CPB) with 45 min of cardioplegic arrest (CA) to establish the AKI model. Baicalin was administered at different doses intragastrically 1 h before CPB. The control and treated rats were subjected to the evaluation of different kidney injury index and inflammation biomarkers. Results: Baicalin significantly attenuated CPB/CA-induced AKI in rats, as evidenced by the lower levels of serum creatinine, serum NGAL, and Kim1. Baicalin remarkably inhibited oxidative stress, reflected in the decreased malondialdehyde and myeloperoxidase activity, and enhanced superoxide dismutase activity and glutathione in renal tissue. Baicalin suppressed the expression of IL-18 and iNOS, and activated the Nrf2/HO-1 pathway. Conclusion: Our data indicated that baicalin mediated CPB/CA-induced AKI by decreasing the oxidative stress and inflammation in the renal tissues, and that baicalin possesses the potential to be developed as a therapeutic tool in clinical use for CSA-AKI.

scholarly journals Nicotine Exposure Exacerbates Development of Cataracts in a Type 1 Diabetic Rat Model

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Nima Tirgan ◽  
Gabriela A. Kulp ◽  
Praveena Gupta ◽  
Adam Boretsky ◽  
Tomasz A. Wiraszka ◽  
...  
Keyword(s):  
Rat Model ◽  
Serum Levels ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Positive Trend ◽  
Sprague Dawley ◽  
Nicotine Treatment ◽  
Sprague Dawley Rats ◽  
Diabetic Rat Model

Diabetes and smoking are known risk factors for cataract development. In this study, we evaluated the effect of nicotine on the progression of cataracts in a type 1 diabetic rat model. Diabetes was induced in Sprague-Dawley rats by a single injection of 65 mg/kg streptozotocin. Daily nicotine injections were administered subcutaneously. Forty-five rats were divided into groups of diabetics with and without nicotine treatment and controls with and without nicotine treatment. Progression of lens opacity was monitored using a slit lamp biomicroscope and scores were assigned. To assess whether systemic inflammation played a role in mediating cataractogenesis, we studied serum levels of eotaxin, IL-6, and IL-4. The levels of the measured cytokines increased significantly in nicotine-treated and untreated diabetic animals versus controls and demonstrated a positive trend in the nicotine-treated diabetic rats. Our data suggest the presence of a synergistic relationship between nicotine and diabetes that accelerated cataract formation via inflammatory mediators.

Decreased RhoA expression in myocardium of diabetic rats

2005 ◽  
Vol 83 (8-9) ◽  
pp. 775-783 ◽  
Author(s):  
Jiping Tang ◽  
Sharyn M Fitzgerald ◽  
Brandi N Boughtman ◽  
Samuel W Cole ◽  
Michael W Brands ◽  
...  
Keyword(s):  
Diabetic Rats ◽  
Small Gtpase ◽  
Control Group ◽  
Diabetic Patients ◽  
Sprague Dawley ◽  
Total Rna ◽  
Sprague Dawley Rats ◽  
Diabetic Myocardium ◽  
Rhoa Protein ◽  
Membrane Bound

Diabetic cardiomyopathy is 1 of the major causes of death in diabetic patients, but the pathogenesis is unclear. There is evidence that RhoA, a small GTPase, might be involved in cardiac function. This study, therefore, analyzed RhoA expression and activation in hearts of diabetic rats. Male Sprague–Dawley rats were divided into control and diabetic groups of 18 each. Diabetes was induced by intravenous injection of streptozotocin (55 mg/kg). Rats were studied 3 weeks after induction of diabetes. Heart rate, which was measured 24 h/day, decreased by 93 ± 7 beats/min in diabetic rats. There was a 62% decrease (p < 0.01) in RhoA mRNA expression in heart tissues (left ventricle) of diabetic rats (38.5 ± 6.7 × 106 molecules/µg total RNA) compared with controls (101 ± 10.3 × 106 molecules/µg total RNA). Western blot showed a 33% decrease in total RhoA protein expression in heart tissues of diabetic rats compared with controls (p < 0.05). A reduced RhoA translocation in heart tissues of diabetic rats was determined by a 64% decrease in membrane-bound RhoA (p < 0.01 vs. control group), indicating that the activation of RhoA is markedly reduced in diabetic myocardium. Our data suggest that down-regulated RhoA may be involved in cardiomyopathy in diabetic rats.Key words: RhoA, diabetes, heart.

scholarly journals Brodifacoum Induces Early Hemoglobinuria and Late Hematuria in Rats: Novel Rapid Biomarkers of Poisoning

2015 ◽  
Vol 41 (4-5) ◽  
pp. 392-399 ◽  
Author(s):  
Kyle M. Ware ◽  
Douglas L. Feinstein ◽  
Israel Rubinstein ◽  
Guy Weinberg ◽  
Brad H. Rovin ◽  
...  
Keyword(s):  
Blood Cells ◽  
Kidney Injury ◽  
Mass Casualty ◽  
Sprague Dawley ◽  
Free Hemoglobin ◽  
Oral Gavage ◽  
Sprague Dawley Rats ◽  
Novel Biomarkers ◽  
Dose Dependent ◽  
Severe Coagulopathy

Introduction: Brodifacoum (BDF) is a superwarfarin that is used primarily as a rodenticide. There have been increasing numbers of reports of human cases of accidental or intentional BDF ingestion with high mortality rate. Its broad availability and high lethality suggest that BDF should be considered a potential chemical threat. Currently, there is no biomarker for early detection of BDF ingestion in humans; patients typically present with severe coagulopathy. Since we demonstrated earlier that warfarin can induce acute kidney injury with hematuria, we tested whether BDF would also lead to change in urinary biomarkers. Material and Methods: BDF was administered to Sprague Dawley rats via oral gavage. N-acetylcysteine (NAC) was given per os in drinking water 24 h prior to BDF. Urinalysis was performed at different times after BDF administration. Anticoagulation and serum creatinine levels were analyzed in the blood. Results: We observed that within a few hours the animals developed BDF-dose-dependent transient hemoglobinuria, which ceased within 24 h. This was accompanied by a transient decrease in hematocrit, gross hemolysis and an increase in free hemoglobin in the serum. At later times, animals developed true hematuria with red blood cells in the urine, which was associated with BDF anticoagulation. NAC prevented early hemoglobinuria, but not late hematuria associated with BDF. Conclusions: We propose that transient early hemoglobinuria (associated with oxidative stress) with consecutive late hematuria (associated with anticoagulation) are novel biomarkers of BDF poisoning, and they can be used in clinical setting or in mass casualty with BDF to identify poisoned patients.

scholarly journals Histological, Biochemical, and Hematological Effects of Goniothalamin on Selective Internal Organs of Male Sprague-Dawley Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Fahmi Kaid ◽  
A. M. Alabsi ◽  
Nashwan Alafifi ◽  
Rola Ali-Saeed ◽  
May Ameen Al-koshab ◽  
...  
Keyword(s):  
Normal Control ◽  
Scientific Data ◽  
Control Group ◽  
Sprague Dawley ◽  
Internal Organs ◽  
Sprague Dawley Rats ◽  
Hematological Effects ◽  
Acute Study ◽  
Isolated Compound ◽  
Higher Doses

Goniothalamin (GTN) is an isolated compound from several plants of the genus Goniothalamus, and its anticancer effect against several cancers was reported. However, there is no scientific data about effects of its higher doses on internal organs. Accordingly, this study aimed to evaluate the acute and subacute effects of higher doses of GTN on the hematology, biochemistry, and histology of selected internal organs of male Sprague-Dawley rats. In acute study, 35 rats were distributed in 5 groups (n=7) which were intraperitoneally (IP) injected with a single dose of either 100, 200, 300, 400, or 500 mg/kg of GTN, while extra 7 rats serve as a normal control. In subacute study, 7 rats were IP-injected with a daily dose of 42 mg/kg of GTN for 14 days, while another 7 rats serve as a normal control group. The normal controls in both studies were IP-injected simultaneously with 2 ml/kg of 10% DMSO in PBS. At the end of both tests, rats were sacrificed to collect blood for hematology and biochemistry and harvest livers, kidneys, lungs, hearts, spleens, and brains for histology. During acute and subacute exposure, no abnormal changes were observed in the hematology, biochemistry, and histology of the internal organs. However, the 300, 400, and 500 mg/kg of GTN during acute exposure were associated with morbidities and mortalities. Ultimately, GTN could be safe up to the dose of 200 mg/kg, and the dose of 42 mg/kg of GTN was tolerated well.

Reduced renal responses to volume expansion in streptozotocin-induced diabetic rats

1989 ◽  
Vol 257 (3) ◽  
pp. R672-R679 ◽  
Author(s):  
K. P. Patel ◽  
P. L. Zhang
Keyword(s):  
Volume Expansion ◽  
Diabetic Rats ◽  
Control Group ◽  
Sprague Dawley ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Sprague Dawley Rats ◽  
Before And After ◽  
Abnormal Volume ◽  
Group A

To determine whether the volume reflex is defective in the diabetic state, the diuretic and natriuretic responses to acute volume expansion (VE) were measured in streptozotocin (STZ)-induced diabetic (Dia) rats. Urine flow (UV) and sodium excretion (UNaV) were measured before and after VE from innervated and denervated kidneys in anesthetized (Inactin 0.1 g/kg, ip) control and Dia rats (Sprague-Dawley rats injected with vehicle or STZ 65 mg/kg ip, respectively, 2 wk before the experiment). Blood glucose levels were significantly elevated in the Dia group compared with the control group. A VE of 1.2 ml/min for 15 min produced a significantly greater diuresis and natriuresis in control rats compared with Dia rats. In addition, reducing the hyperglycemia in Dia rats (third group) by treatment with insulin reversed the blunted UV and UNaV responses to VE. Ratios of UV (innervated-denervated, I/D) before and after VE indicate significant increases in UV by the innervated kidneys, relative to the denervated kidneys in all three groups. I/D ratios of UNa V were not different between the three groups before VE, but were significantly smaller in the Dia rats compared with both control and STZ plus insulin groups after VE. This study demonstrates that 1) there is an abnormal volume reflex in the STZ-induced Dia rats; 2) the natriuresis due to renal sympatho-inhibition is blunted in response to VE in Dia rats; and 3) restoring the glucose levels to normal by insulin treatment in the Dia rats normalizes the volume reflex.

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.

Combination of Naringenin and Lisinopril Ameliorates Nephropathy in Type-1 Diabetic Rats

2020 ◽  
Vol 20 ◽  
Author(s):  
Yogesh A. Kulkarni ◽  
Sachin V. Suryavanshi
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Renal Damage ◽  
Diabetic Rats ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Glycation End Products ◽  
Histopathological Studies ◽  
Diabetes Induction

Background: Diabetes is a metabolic disorder affecting large percentage of population worldwide. Chronic hyperglycemic condition leads to generation of advanced glycation end products, reactive oxygen species and inflammatory cytokines, which worsen functioning of kidney. Clinical management of diabetic nephropathy is difficult as it requires multifocused approach. Hence, Combination of lisinopril a drug used in clinical practice for nephropathy and naringenin, a flavonoid reported to have significant effect in nephropathy may show additive of synergistic effect with less side effects. Objective: The objective of present study was to evaluate the effect of combination of lisinopril with naringenin in diabetic nephropathy. Methods: Diabetes was induced in male Sprague Dawley rats by streptozotocin (55 mg/kg, i.p.). After four weeks of diabetes induction animals were treated with naringenin alone and combination of Lisinopril and naringenin for next four weeks. At the end of study, various urine and biochemical parameters were evaluated. Oxidative stress parameters like malondialdehyde, reduced glutathione; catalase and superoxide dismutase for kidney tissues were estimated and histopathology studies of kidney were carried out. Results: Combination of lisinopril (10 mg/kg) and naringenin (25 and 50 mg/kg) treatment showed significant improvement in the biochemical and urine parameters. Combination treatment also attenuated renal oxidative stress and renal damage as observed in histopathological studies. Conclusion: Treatment with combination of lisinopril and naringenin showed promising effect in diabetic nephropathy in rats.

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