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 ◽  
...  

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.

Author(s):  
Min Hu ◽  
Fan Du ◽  
Shi Liu

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.


2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Khadijah Saeed Balamash ◽  
Huda Mohammed Alkreathy ◽  
Elham Hamed Al Gahdali ◽  
Sawsan Omer Khoja ◽  
Aftab Ahmad

Treatment of diabetic patients with antioxidant, such as extra virgin olive oil (EVOO), may be beneficial in numerous debilitating complexities. This study was aimed at assessing the protective role of virgin olive oil in reducing hyperglycemia in streptozotocin- (STZ-) induced diabetic rats. Thirty-six healthy male Sprague-Dawley rats were divided into six groups (6 rats per group) including nondiabetic control (NC), diabetic control (DC), and animals treated with metformin, olive oil, and a combination of olive oil and metformin, respectively. The protective effect of olive oil was evaluated by determining the biochemical parameters (lipid profile, liver, and kidney) and by studying the histopathological alterations in pancreas, liver, and kidney tissues. The results showed a significant increase in alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels in diabetic rats. ALP levels remained significantly elevated in the diabetic rats that were treated with metformin and/or olive oil, and the highest level was noted in the group treated with olive oil (568.33 U/L). Contrarily, pretreatment with olive oil significantly decreased ALT (67.64 U/L) and ALP (226.17 U/L) levels. Histopathological data revealed that all the disorganized islets of Langerhans along with the clusters of inflammatory cells were absent in the group pretreated with the combination of virgin olive oil and metformin, which shows that prophylactic administration of this combination reduces the diabetic complications in a much better way. Therefore, pretreatment with olive oil with or without metformin is an encouraging approach for diabetes therapy with immense potential.


1989 ◽  
Vol 257 (3) ◽  
pp. R672-R679 ◽  
Author(s):  
K. P. Patel ◽  
P. L. Zhang

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.


2015 ◽  
Vol 22 (12) ◽  
pp. 1560-1564
Author(s):  
Mohammad Afzal Khan ◽  
Faris Mohammed Nour Altaf ◽  
Muhammad Naeem Chaudhry

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.


2014 ◽  
Vol 58 (6) ◽  
pp. 630-639 ◽  
Author(s):  
Yan Xing ◽  
Shandong Ye ◽  
Yumi Chen ◽  
Wen Hu ◽  
Yan Chen

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.


2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Ehsan Zandifar ◽  
Sajedeh Sohrabi Beheshti ◽  
Alireza Zandifar ◽  
Shaghayegh Haghjooy Javanmard

We aimed to investigate whether oral administration of captopril modulate wound healing, nitric oxide (NO), and vascular endothelial growth factor (VEGF) concentration in wound fluid of diabetic rats. 48 male Sprague-Dawley rats were divided in four groups (n=12). The 36 rats were rendered diabetic by streptozotocin. The animals of the first and second groups received 25 and 50 mg/kg/day captopril, respectively, (DM-cap25 and DM-cap50). The animals of the third group were treated by distilled water (DM-control). Control rats had no intervention. The wound fluid level of NO and VEGF were measured. Wound specimens were investigated histopathologically. At the 5th day, there was significantly moreNOxin wound fluid of DM-cap25 compared to other groups. At the 7th day, both captopril-treated groups had moreNOxin wound fluid compared to other groups. At the 11th day, both captopril-treated groups had moreNOxin wound fluid compared to DM-control group. VEGF concentration was significantly higher in both captopril-treated groups versus DM-control group (P<.05). There were significant higher wound healing scores in captopril-treated groups compared with DM-control group (P<.05). These results suggest that captopril might be useful in diabetic wound healing.


Author(s):  
Xiangyu Liu ◽  
Xiong Xue ◽  
Junsheng Tian ◽  
Xuemei Qin ◽  
Shi Zhou ◽  
...  

The objectives of this study were to compare the antidepressant effects between endurance and resistance exercise for optimizing interventions and examine the metabolomic changes in different types of skeletal muscles in response to the exercise, using a rat model of chronic unpredictable mild stress (CUMS)-induced depression. There were 32 male Sprague-Dawley rats randomly divided into a control group (C) and 3 experimental groups: CUMS control (D), endurance exercise (E), and resistance exercise (R). Group E underwent 30 min treadmill running, and group R performed 8 rounds of ladder climbing, 5 sessions per week for 4 weeks. Body weight, sucrose preference, and open field tests were performed pre and post the intervention period for changes in depressant symptoms, and the gastrocnemius and soleus muscles were sampled after the intervention for metabolomic analysis using the 1H-NMR technique. The results showed that both types of exercise effectively improved the depression-like symptoms, and the endurance exercise appeared to have a better effect. The levels of 10 metabolites from the gastrocnemius and 13 metabolites from the soleus of group D were found to be significantly different from that of group C, and both types of exercise had a callback effect on these metabolites, indicating that a number of metabolic pathways were involved in the depression and responded to the exercise interventions.


2009 ◽  
Vol 29 (2) ◽  
pp. 93-101 ◽  
Author(s):  
Amal A El-Bakary ◽  
Sahar A El-Dakrory ◽  
Sohayla M Attalla ◽  
Nawal A Hasanein ◽  
Hala A Malek

Methanol poisoning is a hazardous intoxication characterized by visual impairment and formic acidemia. The therapy for methanol poisoning is alcohol dehydrogenase (ADH) inhibitors to prevent formate accumulation. Ranitidine has been considered to be an inhibitor of both gastric alcohol and hepatic aldehyde dehydrogenase enzymes. This study aimed at testing ranitidine as an antidote for methanol acute toxicity and comparing it with ethanol and 4-methyl pyrazole (4-MP). This study was conducted on 48 Sprague-Dawley rats, divided into 6 groups, with 8 rats in each group (one negative control group [C1], two positive control groups [C2, C3] and three test groups [1, 2 and 3]). C2, C3 and all test groups were exposed to nitrous oxide by inhalation, then, C3 group was given methanol (3 g/kg orally). The three test groups 1, 2 and 3 were given ethanol (0.5 g/kg orally), 4-MP (15 mg/kg intraperitoneally) and ranitidine (30 mg/kg intraperitoneally), respectively, 4 hours after giving methanol. Rats were sacrificed and heparinized, cardiac blood samples were collected for blood pH and bicarbonate. Non-heparinized blood samples were collected for formate levels by high performance liquid chromatography. Eye balls were enucleated for histological examination of the retina. Ranitidine corrected metabolic acidosis (p = .025), decreased formate levels (p = .014) and improved the histological findings in the retina induced by acute methanol toxicity.


Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 723-723
Author(s):  
Qing-Feng Tao ◽  
Diego Martinez vasquez ◽  
Ricardo Rocha ◽  
Gordon H Williams ◽  
Gail K Adler

P165 Aldosterone through its interaction with the mineralocorticoid receptor (MR) plays a critical role in the development of hypertension and cardiovascular injury (CVI). Normally, MR is protected by 11β-hydroxysteroid dehydrogenase (11β-HSD) which inactivates glucocorticoids preventing their binding to MR. We hypothesis that if activation of MR by either aldosterone or glucocorticoids induces hypertension and CVI, then the inhibition of 11β-HSD with glycyrrhizin (GA), a natural inhibitor of 11β-HSD, should induce damage similar to that observed with aldosterone. Sprague-Dawley rats were uninephrectomized, and treated for 4 weeks with 1% NaCl (in drinking water) for the control group, 1% NaCl + aldosterone infusion (0.75 μg/h), or 1% NaCl + GA (3.5 g/l in drinking water). After 4 weeks, aldosterone and GA caused significant increases in blood pressure compared to control rats ([mean ± SEM] 211± 9, 205 ± 12, 120 ± 9 mmHg, respectively, p<0.001). Both aldosterone- and GA-treated rats had a significant increase in proteinuria (152.2 ± 8.7 and 107.7 ± 19.5 mg/d, respectively) versus controls (51.2 ± 9.5 mg/d). There was a significant increase (p<0.001) in heart to body weight ratio in the rats treated with aldosterone or GA compared with control (3.92 ± 0.10, 3.98 ± 0.88, and 3.24 ± 0.92 mg/g, respectively). Hearts of GA and aldosterone treated rats showed similar histological changes consisting of biventricular myocardial necrosis and fibrinoid necrosis of small coronary arteries and arterioles. These data suggests that in rodents activation of MR by either aldosterone or corticosterone leads to severe hypertension, vascular injury, proteinuria and myocardial infarction. Thus, 11β-HSD plays an important role in protecting the organism from injury.


2012 ◽  
Vol 27 (5) ◽  
pp. 301-305 ◽  
Author(s):  
Baohua Zhu ◽  
Chuanming Tong ◽  
Weitao Guo ◽  
Rong Pu ◽  
Guoping Zhang ◽  
...  

PURPOSE: To investigate synergistic suppression of donor liver pre-perfusion with recipient serum (RS) and cobra venom factor (CVF) treatment on hyperacute rejection (HAR) following liver xenotransplantation. METHODS: Guinea-pigs (GP, n=24) and Sprague-Dawley rats (SD, n=24) were recruited. Before transplantation, serum was collected from SD rats and used for preparation of inactivated complements. GP and SD rats were randomly assigned into four groups (n=6), respectively: RS group, CVF group, RS+CVF group and control group. Orthotopic liver xenotransplantation was performed with modified two-cuff technique. The survival time and liver function of recipients, morphological and pathological changes in rat livers were investigated. RESULTS: There was no piebald like change in the recipient livers in all experiment groups. The survival time of recipients in all experiment groups was longer than that in control group (p<0.05). Moreover, the survival time in the RS+CVF group was markedly longer than that in the RS group (p<0.01) and CVF group (p<0.05). The serum ALT level in all experiment groups were lower than that in the control group (p<0.05). Furthermore, the ALT level in the RS+CVF group was significantly lower than that in the CVF group (p<0.05) and RS group (p<0.01). The histological damages were significantly improved when compared with the control group, and the histological damages in the RS+CVF group were milder than those in the remaining groups (p<0.05) CONCLUSION: Pre-perfusion of donor liver with recipient serum and cobra venom factor treatment can exert synergistic suppressive effects on the hyperacute rejection following liver xenotransplantation.


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