Selenium restores defective beta-adrenergic receptor response of thoracic aorta in diabetic rats

Zeydanli, Esma N.; Bilginoglu, Ayca; Tanriverdi, Evrim; Gürdal, Hakan; Turan, Belma

doi:10.1007/s11010-009-0353-5

Cited by 14 publications

(26 citation statements)

References 38 publications

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“…Diabetes was induced in 3-month-old male Wistar rats as described previously [15,16]. A week after injection of streptozotocin (STZ; 50 mg/kg, single injection as intraperitoneal), blood glucose level was measured by using a glucose analyser (Glucotrend, Roche).…”

Section: Diabetic Rat Modelmentioning

confidence: 99%

“…The frozen aortas were pulverized at liquid nitrogen temperature and then homogenized as described previously [15,16]. Protein content was analyzed using the Bradford method (Bio-Rad), and bovine serum albumin was used as the standard.…”

Section: Preparation Of Aorta Homogenatesmentioning

confidence: 99%

“…Yet, little is known about the effect of hyperglycemia on regulation and contribution of MMPs in the vascular system dysfunction. Moreover, we have shown recently that the activity of MMPs such as MMP-2 and MMP-9 and their tissue inhibitor TIMP-4 are significantly depressed in thoracic aorta from diabetic rats, and either sodium selenate or omega-3E treatment significantly regulated the depressed activity of MMPs via preventing oxidative injury and consequently improved impaired vascular responses [15,16].…”

Section: Introductionmentioning

confidence: 99%

“…Our previous studies suggest that there is a relationship between MMPs and impaired vascular functions of the diabetic rats [15,16]. We used either doxycycline or antioxidants (selenium or omega-3E) to treat STZ-induced diabetic rats, and then investigated heart function as well as the status of MMPs in these tissues [28,29].…”

Section: Introductionmentioning

confidence: 99%

“…We used either doxycycline or antioxidants (selenium or omega-3E) to treat STZ-induced diabetic rats, and then investigated heart function as well as the status of MMPs in these tissues [28,29]. In addition, we studied the vascular function in diabetic rats treated with selenium or omega-3E [15,16]. In those studies, the functional and biochemical analysis in heart and vascular tissues demonstrated that the beneficial effects of doxycycline treatment are closely matching to those of the antioxidants.…”

Section: Introductionmentioning

confidence: 99%

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Doxycycline Ameliorates Vascular Endothelial and Contractile Dysfunction in the Thoracic Aorta of Diabetic Rats

2011

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Studies have shown that tetracycline class antibiotics exhibit an ameliorating action with its antioxidant property on increased oxidative stress in tissues, including heart. Since endothelial vascular dysfunction in diabetes is associated with increased oxidative stress and prevented with antioxidants, herein, we aimed to test a hypothesis whether a low-dose doxycycline treatment of diabetic rats for 4 weeks can ameliorate endothelial vascular dysfunction of thoracic aortas. Results of the present study shows that both direct and alpha receptor-mediated contractile responses as well as endothelium-dependent and endothelium-independent vasodilatory responses were preserved with low-dose doxycycline treatment (30 μmol/kg, daily; for 4 weeks) compared with untreated diabetic group. Furthermore, doxycycline treatment normalized increased lipid peroxidation and cellular glutathione level measured in plasma and prevented diabetes-induced impaired body weight gain without significant effect on high blood glucose level. Increased membrane protein level of caveolin-1, elevated ratio of PKC in particulate and cytosolic fraction, and increased protein level of cytosolic endothelin-1 in diabetic rats were also significantly prevented with doxycycline treatment. Moreover, diabetes-induced another type of oxidative stress markers in rats, matrix metalloproteinases, MMP-2, and MMP-9 were also normalized with doxycycline treatment in blood. Taken together, our data address that amelioration and/or prevention of vascular endothelial and contractile dysfunction by doxycycline is accompanied by a clear reduction in oxidative stress markers of diabetes, which provides evidence for doxycycline's potential antioxidant action as a therapeutic agent for amelioration and/or prevention of vascular disorders in diabetic subjects.

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Section: Diabetic Rat Modelmentioning

confidence: 99%

Section: Preparation Of Aorta Homogenatesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Doxycycline Ameliorates Vascular Endothelial and Contractile Dysfunction in the Thoracic Aorta of Diabetic Rats

2011

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Comparative investigation of kidney mesangial cells from increased oxidative stress-induced diabetic rats by using different microscopy techniques

2013

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High glucose and increased oxidative stress levels are the known important mediators of diabetic nephropathy. However, the effects of these mediators on tissue damage basically due to extracellular matrix expansion in mesangial cells have yet to be fully examined within the context of early stage diabetic nephropathy. In this study, we attempted to characterize changes in mesangial cells of streptozotocin-induced diabetic rats with a comparative investigation of kidney tissue by using different microscopy techniques. The serum levels of urea and creatinine of diabetic rats, as biomarkers of kidney degeneration, decreased significantly compared to those of age-matched controls. In diabetic rats, there are increased malondialdehyde and oxidized-glutathione levels as well as reduced-glutathione and glutathione-peroxidase activity levels in renal tissue compared to those of the controls. By using light and electron microscopies, we showed that there were marked thickening in Bowman's membrane and glomerular capillary wall, increased amount of extracellular matrix often occupying Bowman's space, degenerations in tubules, an increased number of mesangial cells in the network of glomerular capillary walls, and increased amount of lipid accumulation in proximal tubules in the renal tissue of diabetic rats. Our confocal microscopy data confirmed also the presence of irregularity and widened in glomerular capillaries, their attachment to the Bowman's capsule, degenerated heterochromatin, thickening in foci of glomerular basement membrane, and marked increase in mesangial cells. These results suggest that a detailed structural investigation of kidney tissue provides further information on the important role of mesangial cells in pathogenesis of diabetic nephropathy.

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Di-peptidyl peptidase-4 inhibitor sitagliptin protects vascular function in metabolic syndrome: possible role of epigenetic regulation

et al. 2014

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Metabolic syndrome (MetS) is a complex medical disorder characterized by insulin resistance, hypertension, and high risk of coronary disease and stroke. Microvascular rarefaction and endothelial dysfunction have also been linked with MetS, and recent evidence from clinical studies supports the efficacy of incretin-based antidiabetic therapies for vascular protection in diabetes. Previous studies pointed out the importance of dipeptidyl peptidase-4 (DPP-4) inhibition in endothelial cells due to getting protection against metabolic pathologies. We therefore aimed to investigate the acute effects of a DPP-4 inhibitor, sitagliptin, on vascular function in rats with high-sucrose diet-induced MetS. In order to elucidate the mechanisms implicated in the effects of DPP-4 inhibition, we tested the involvement of NO pathway and epigenetic regulation in the MetS. Acute use of sitagliptin protects the vascular function in the rats with MetS in part due to NO pathway via restoring the depressed aortic relaxation responses mediated by receptors. Application of sitagliptin enhanced the depressed phosphorylation levels of both the endothelial NO synthase and the apoptotic status of protein kinase B, known as Akt, in endothelium-intact thoracic aorta from rats with MetS. One-hour application of sitagliptin on aortic rings from rats with MetS also induced remarkable histon posttranslational modifications such as increased expression of H3K27Me3, but not of H3K27Me2, resulting in an accumulation of the H3K27Me3. Our findings suggest that, in addition to its well-known hypoglycemic action, sitagliptin may also have beneficial effects on hyperglycemia-induced vascular changes in an endotheium-dependent manner. These present results with sitagliptin aside from the glycaemic control, may demonstrate its important role in the treatment of patients with MetS.

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Selenium restores defective beta-adrenergic receptor response of thoracic aorta in diabetic rats

Cited by 14 publications

References 38 publications

Doxycycline Ameliorates Vascular Endothelial and Contractile Dysfunction in the Thoracic Aorta of Diabetic Rats

Doxycycline Ameliorates Vascular Endothelial and Contractile Dysfunction in the Thoracic Aorta of Diabetic Rats

Comparative investigation of kidney mesangial cells from increased oxidative stress-induced diabetic rats by using different microscopy techniques

Di-peptidyl peptidase-4 inhibitor sitagliptin protects vascular function in metabolic syndrome: possible role of epigenetic regulation

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