scholarly journals Serotonin-promoted elevation of ROS levels may lead to cardiac pathologies in diabetic rat

2015 ◽  
Vol 67 (2) ◽  
pp. 655-661 ◽  
Author(s):  
Tahir Ali ◽  
Farhat Shaheen ◽  
Madiha Mahmud ◽  
Hina Waheed ◽  
Muhammad Ishtiaq ◽  
...  

Patients with diabetes mellitus (DM) develop tendencies toward heart disease. Hyperglycemia induces the release of serotonin from enterochromaffin cells (EC). Serotonin was observed to elevate reactive oxygen species (ROS) and downregulate antioxidant enzymes. As a result, elevated levels of serotonin could contribute to diabetic complications, including cardiac hypertrophy. In the present study, diabetes mellitus was induced in rats by alloxan administration; this was followed by the administration of serotonin to experimental animals. ROS, catalase (CAT), superoxide dismutase (SOD), B-type natriuretic peptide (BNP) expression, and histopathological assessments were performed. Elevated ROS concentrations and decreased antioxidant enzyme activities were detected. Further, we observed an increase in cell surface area and elevated BNP expression which suggests that events associated with cardiac hypertrophy were increased in serotonin-administered diabetic rats. We conclude that serotonin secretion in diabetes could contribute to diabetic complications, including cardiac hypertrophy, through enhanced ROS production.

2017 ◽  
Vol 95 (11) ◽  
pp. 1343-1350
Author(s):  
Aleksandra Vranic ◽  
Stefan Simovic ◽  
Petar Ristic ◽  
Tamara Nikolic ◽  
Isidora Stojic ◽  
...  

Currently, cardiovascular diseases are the leading cause of global mortality, while diabetes mellitus remains an important cause of cardiovascular morbidity. A recent study showed that patients with diabetes mellitus treated with mineralocorticoid receptor antagonists have improved coronary microvascular function, leading to improved diastolic dysfunction. In this study, we evaluated the influence of acute administration of spironolactone on myocardial function in rats with streptozotocin-induced diabetes mellitus, with special emphasis on cardiodynamic parameters in diabetic rat hearts. The present study was carried out on 40 adult male Wistar albino rats (8 weeks old). Rats were randomly divided into 4 groups (10 animals per group): healthy rats treated with 0.1 μmol/L of spironolactone, diabetic rats treated with 0.1 μmol/L of spironolactone, healthy rats treated with 3 μmol/L of spironolactone, and diabetic rats treated with 3 μmol/L of spironolactone. Different, dose-dependent, acute responses of spironolactone treatment on isolated, working diabetic and healthy rat heart were observed in our study. In healthy rats, better systolic function was achieved with higher spironolactone dose, while in diabetic rats, similar effects of low and high spironolactone dose were observed.


2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Christian Ottomann ◽  
Markus Küntscher ◽  
Bernd Hartmann ◽  
Vlado Antonic

Ischaemic insult in the skin flaps is a major problem in reconstructive surgery particularly in patients with diabetes mellitus. Here, we sought to investigate the effectiveness of ischaemic preconditioning (IP) on diabetic skin flaps in rat animal model. Hundred Wistar rats (90 streptozotocin treated animals and 10 nondiabetic controls) were used. Diabetes mellitus was confirmed by measuring glucose level in blood, HbA1c, and ketonuria. We used blood vessel clamping, hind limb tourniquet, and NO donors (Spermine/NO complex) to induce short-term ischaemia of tissues that will be excised for skin flaps. Animals were followed for 5 days. Flaps were photographed at day 5 and percent of necrosis was determined using planimetry. Significant decrease in percent of necrotic tissue in all groups that received preconditioning was observed. Results show that ischaemic preconditioning suppresses flap necrosis in diabetic rats irrespective of direct or remote tissue IP and irrespective of chemically or physically induced preischaemia. Spermine/NO complex treatment 10 minutes after the flap ischaemia suppressed tissue necrosis. Treatment with NO synthase inhibitor L-NAME reversed effects of IP showing importance of NO for this process. We show that IP is a promising approach for suppression of tissue necrosis in diabetic flaps and potential of NO pathway as therapeutic target in diabetic flaps.


2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Gabriela Gambato ◽  
Elisa Maria Pavão ◽  
Gabriela Chilanti ◽  
Roselei Claudete Fontana ◽  
Mirian Salvador ◽  
...  

Hyperglycaemia exacerbates the production of reactive oxygen species (ROS), contributing to the multiple complications associated with diabetes. Mitochondrial dysfunction is also known to be associated with diabetes. Therefore, the aim of this work was to study the effect of Pleurotus albidus extract on the mitochondrial dysfunction induced by hyperglycaemia in EA.hy926 endothelial cells. The results showed that P. albidus treatment prevented the increase in the activity of complex I of the electron transport chain and minimized the ROS production induced by hyperglycaemia. In addition, the extract minimized oxidative damage to lipids and proteins, caused an imbalance in the antioxidant enzyme activities of superoxide dismutase and catalase, and decreased the nitric oxide levels induced by hyperglycaemia. These data contribute to our understanding of the mitochondrial disorder induced by hyperglycaemia as well as establishing the conditions required to minimize these alterations.


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.


2016 ◽  
Vol 2016 ◽  
pp. 1-10
Author(s):  
P. P. Wołkow ◽  
B. Bujak-Giżycka ◽  
J. Jawień ◽  
R. Olszanecki ◽  
J. Madej ◽  
...  

Purpose. Products of angiotensin (ANG) I metabolism may predispose to vascular complications of diabetes mellitus. Methods. Diabetes was induced with streptozotocin (75 mg/kg i.p.). Rat aorta fragments, isolated 4 weeks later, were pretreated with perindoprilat (3 μM), thiorphan (3 μM), or vehicle and incubated for 15 minutes with ANG I (1 μM). Products of ANG I metabolism through classical (ANG II, ANG III, and ANG IV) and alternative (ANG (1–9), ANG (1–7), and ANG (1–5)) pathways were measured in the buffer, using liquid chromatography-mass spectrometry. Results. Incubation with ANG I resulted in higher concentration of ANG II (P = 0.02, vehicle pretreatment) and lower of ANG (1–9) (P=0.048, perindoprilat pretreatment) in diabetes. Preference for the classical pathway is suggested by higher ANG III/ANG (1–7) ratios in vehicle (P=0.03), perindoprilat (P=0.02), and thiorphan pretreated (P=0.02) diabetic rat. Within the classical pathway, ratios of ANG IV/ANG II (P=0.01) and of ANG IV/ANG III (P=0.049), but not of ANG III/ANG II are lower in diabetes. Conclusions. Diabetes in rats led to preference toward deleterious (ANG II, ANG III) over protective (ANG IV, ANG (1–9), and ANG (1–7)) ANG I metabolites.


Author(s):  
Diana Holidah ◽  
Ika Puspita Dewi ◽  
Fransiska Maria Christianty ◽  
Noer Sidqi Muhammadiy ◽  
Nur Huda

Diabetes mellitus is a syndrome due to disorders of carbohydrate, lipid, and protein metabolism due to decreased insulin secretion or reduced insulin sensitivity. The number of people with diabetes mellitus is increasing every year. However, diabetes mellitus is a major cause of cardiovascular disease, blindness, kidney failure, and amputation due to gangrene. Patients with diabetes mellitus have a possibility of 2-3 times higher cardiovascular disease than non diabetic. Sappan wood containing brazilin that have antioxidant activity and had a potential activity to lower the incidence of type 2 diabetes mellitus. Objective of this research was to determine the activity of secang wood extract as an antidiabetic and antidyslipidemic on diabetic rat. Diabetic rat induced by alloxan and given extract once daily for 14 days. At 15th day, blood glucose level, lipid profile was determine, pancreas was harvested and processed to hystopathological examination. Secang wood extract decreased blood glucose, cholesterol, triglyceride, and LDL level, increase HDL level, and repair the histology of pancreas on diabetic rat after 14 days treatment. Based on the result, secang wood extract had antidiabetic and antidyslipidemic activity on diabetic rat.


2002 ◽  
Vol 14 (8) ◽  
pp. 479 ◽  
Author(s):  
Carolina Pustovrh ◽  
Alicia Jawerbaum ◽  
Débora Sinner ◽  
Verónica White ◽  
Evangelina Capobianco ◽  
...  

Matrix metalloproteinases (MMPs) are responsible for the remodelling of the uterine extracellular matrix during embryo implantation. Nitric oxide (NO) production is increased at the time when implantation begins. Abnormal tissue levels of MMPs are present in diabetes; elevated NO levels in tissues and an increased oxidative stress are also found. The present work evaluates the uterine MMP2 activity and levels during embryo implantation, as well as the influence of nitridergic compounds and reactive oxygen species (ROS) on the MMP2 enzymatic activity in a model of neonatal streptozotocin-induced diabetic rat. Metalloproteinase 2 activity and levels are increased in diabetic tissues compared with controls (P<0.05 and P<0.002 respectively). The uterine enzymatic activity in diabetic animals decreases in the presence of the NOS inhibitor NG-nitro-L-arginine methyl ester (P<0.01) and is enhanced (P<0.005) when a generating ROS system (xanthine/xanthine oxidase) is added to the incubating medium. It was also found that uterine superoxide dismutase activity is higher in diabetic rats than in control rats on the day of implantation (P<0.001), suggesting a compensatory antioxidant ability. In conclusion, the results show that the uterine MMP2 activity, which is higher in diabetic animals than in control animals, is modulated positively by NO and ROS during embryo implantation in a model of streptozotocin-induced diabetic rats.


1999 ◽  
Vol 77 (12) ◽  
pp. 980-985 ◽  
Author(s):  
Jean-François Bouchard ◽  
Éric C Dumont ◽  
Daniel Lamontagne

Functional dilatory response in streptozotocin-induced diabetic rats was investigated using thoracic aortas, isolated hearts, and mesenteric beds. Dose-response curves to the PGI2 analogue iloprost on phenylephrine-preconstricted rings of diabetic rats and controls were comparable. In contrast, decreased vasodilation in diabetic rats was observed when dose-response curves to iloprost were performed in hearts and on phenylephrine-preconstricted mesenteric beds. Dose-response curves to forskolin, an adenylyl cyclase activator, performed with hearts and phenylephrine-preconstricted aortic rings and isolated mesenteric beds of diabetic rats and controls were comparable. However, a decreased vasodilation to the ATP-sensitive potassium channel (KATP) activator lemakalim was observed in diabetic hearts, but not in aortic rings and mesenteric beds. In conclusion, under our experimental conditions, diabetes mellitus affects the vasodilation to iloprost in both coronary and mesenteric beds, but not in the aorta. In the heart, this modification of vascular reactivity may be due to a decrease in KATP channel mediated response and not to a decreased activity of adenylyl cyclase. At this time, in the isolated mesenteric bed, the mechanism of this modification in vascular reactivity remains unknown.Key words: diabetes mellitus, iloprost, KATP channels, adenylyl cyclase, aorta, coronary circulation, mesenteric bed.


2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Bonaventure Chukwunonso Obi ◽  
Theophine Chinwuba Okoye ◽  
Victor Eshu Okpashi ◽  
Christiana Nonye Igwe ◽  
Edwin Olisah Alumanah

Diabetes mellitus is one of the serious global health problems affecting a significant proportion of both developed and developing countries. Overproduction of free radicals and oxidative stress has been associated with the development of diabetic complications. In the present study, the antioxidant effects of metformin (MET), glibenclamide (GLI), and repaglinide (REP) were evaluated in alloxan-induced diabetic rats. The findings from this study may possibly help in understanding the efficacy of these standard drugs in managing the complications arising from diabetes mellitus (DM). Alloxan (130 mg/kg BW) was administered as a single dose to induce diabetes. Four (4) groups of rats (n=6) were used; group 1 served as diabetic control while groups 2, 3, and 4 were the diabetic test groups that received MET (25 mg/kg), GLI (2.5 mg/kg), and REP (0.5 mg/kg), respectively. The result of the study showed significant (p<0.05) improvement in the altered antioxidant enzymes (SOD, CAT) and GSH concentration in diabetic treated rats compared with the diabetic control group. MET and REP produced significant effect on the MDA concentration while GLI showed insignificant reduction in the MDA concentration compared with the diabetic control. Findings from this study suggest that the administration of MET, GLI, and REP exerts significant antioxidant effects in alloxan-induced diabetic rats, thus contributing to the protective effect against oxidative stress-induced damage during diabetic complications.


2017 ◽  
Vol 126 (01) ◽  
pp. 7-13
Author(s):  
Dimitrios Oikonomou ◽  
Jan Benedikt Groener ◽  
Ruan Cheko ◽  
Zoltan Kender ◽  
Lars Kihm ◽  
...  

AbstractThere is growing evidence that reactive metabolites, such as reactive oxygen species and dicarbonyls contribute to diabetic complications. Formation, accumulation, and detoxification of these metabolites are controlled by several enzymes, some of which have genetically determined levels of expression or function. This review not only gives an overview of the different SNPs studied in patients with diabetes mellitus type 1 and type 2, but in addition attempts to bridge the gap between a genetic study and clinical use. Therefore, not only the results of the studies are reviewed, but also their use in identification of subgroups where an increased or decreased risk for a diabetic complication is described, as well as their use in developing novel therapeutic options based on understanding the contribution of an enzyme to a given complication.


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