Agonist Rosiglitazone (agonist + rosiglitazone)

Distribution by Scientific Domains


Selected Abstracts


Mistletoe lectin-I augments antiproliferative effects of the PPAR, agonist rosiglitazone on human malignant melanoma cells

PHYTOTHERAPY RESEARCH, Issue 9 2010
Christian Freudlsperger
Abstract As malignant melanoma cells are highly resistant to conventional chemotherapy, survival rates after tumor spread remain poor and hence there is an urgent need for new therapeutic options. For both mistletoe lectin-I (ML-I) and the thiazolidinediones as synthetic ligands of the peroxisome proliferator-activated receptor , (PPAR,) an antiproliferative effect on malignant melanoma cells has previously been shown. Hence, the aim of this study was to investigate whether the combination of ML-I and the PPAR, ligand rosiglitazone is more efficacious in the treatment of malignant melanoma cells than either agent alone. Proliferation of three human melanoma cell lines treated with ML-I, rosiglitazone and the combination of both was measured in a broad concentration range (0.0001,100,,g/mL) using the XTT cell proliferation assay. Combined application tremendously increased the antiproliferative effect on all three melanoma cell lines compared with single agent treatment. In comparison with the single use of rosiglitazone, the combination with ML-I significantly increased the inhibition of cell growth by 51,79% and in comparison with the single use of ML-I by 9,32%, respectively. In conclusion, this study shows that the combination of ML-I with rosiglitazone significantly augments their antiproliferative effect on malignant melanoma cells in comparison with their single agent application, which might be a promising tool for further therapeutic studies. Copyright © 2010 John Wiley & Sons, Ltd. [source]


Peroxisome proliferator-activated receptor-gamma agonist rosiglitazone reduces the size of experimental endometriosis in the rat model

AUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 4 2007
Hakan AYTAN
Abstract Background:, The effect of rosiglitazone, an activator of peroxisome proliferator-activated receptor-gamma, on the growth of ectopic uterine tissue was assessed. Methods:, Endometriosis was surgically induced in 28 rats by transplanting an autologous fragment of endometrial tissue onto the inner surface of the abdominal wall. Four weeks later, rats were randomly grouped and a second laparatomy was performed. The length, width, height and volume of the explants were measured. Rosiglitazone at 0.2 mg/kg/day was orally administered to one group, while vehicle treatment was given to the control group. Four weeks later, rats were sacrificed and ectopic uterine tissues were re-evaluated morphologically and histologically. Scoring system was used to evaluate the preservation of epithelia. Results:, One rat in the study group and two rats in the control group died as a result of complications related to surgery. There was a significant difference in post-treatment length, width, height, and spherical volumes between control and rosiglitazone-treated groups. The epithelia were found to be preserved significantly better in the control group when compared with the rosiglitazone-treated group. Conclusion:, Rosiglitazone was found to cause regression of experimental endometriosis in rats. [source]


Rosiglitazone via upregulation of Akt/eNOS pathways attenuates dysfunction of endothelial progenitor cells, induced by advanced glycation end products

BRITISH JOURNAL OF PHARMACOLOGY, Issue 8 2009
Chun Liang
Background and purpose:, Advanced glycation end products (AGEs) and endothelial progenitor cells (EPCs) play key roles in pathogenesis of diabetes-related vascular complications. AGEs can induce dysfunction in EPCs. The peroxisome proliferator-activated receptor-gamma (PPAR,) agonists are widely used in the treatment of type 2 diabetes, and it remains unknown if they could attenuate EPC dysfunction induced by AGEs. Experimental approach:, EPCs isolated from healthy adults were cultured with various concentrations of AGEs (0, 50, 100 and 200 mg·L,1) with or without rosiglitazone (10 nM), antibody for the receptors for AGE-human serum albumin (anti-receptor for advanced glycation end products (RAGE); 50 µg·mL,1), phosphatidylinositol-3-kinase (PI3K) inhibitor (LY294002, 5 µM), nitric oxide (NO) synthase inhibitor (L-NG -nitro-arginine methyl ester (L-NAME), 100 µM) or sodium nitroprusside (SNP, 25 µM). Proliferation, apoptosis, cell adhesion, migration and NO production in EPCs were assessed, and expressions of endothelial NO synthase (eNOS) and Akt were determined. Key results:, Number, proliferation/migration capacities, eNOS and Akt phosphorylation as well as NO synthesized by EPCs were increased by rosiglitazone and reduced by AGEs. AGEs promoted while rosiglitazone reduced EPC apoptosis. The AGE-induced effects were significantly ameliorated by pre-incubation with rosiglitazone, RAGE antibody and SNP. The beneficial effects of rosiglitazone could be blocked by pretreatment with L-NAME and LY294002. Conclusions and implications:, The PPAR, agonist rosiglitazone increased EPC function and attenuated EPC dysfunction induced by AGEs via upregulating the Akt-eNOS signal pathways of EPCs. [source]


Effects of retinoids and thiazolidinediones on proliferation, insulin release, insulin mRNA, GLUT 2 transporter protein and mRNA of INS-1 cells

CELL BIOCHEMISTRY AND FUNCTION, Issue 3 2001
J. Blumentrath
Abstract Both 9-cis-retinoic acid (9cRA) and all-trans-retinoic acid (ATRA) are active metabolites of vitamin A (retinol). There exists an interaction between retinoid receptors and peroxisome proliferator-activated receptors (PPAR,). To define their functions in an insulin secreting system the effects of ATRA, 9cRA and the PPAR, agonist rosiglitazone on cell proliferation, insulin release and glucose transporter (GLUT) 2 of INS-1 cells were tested. Retinoic acid receptor (RAR-, and -,) and retinoid X receptor (RXR-, and -,) proteins are present (immunoblots). Both 9cRA and ATRA inhibit INS-1 cell proliferation ([3H]-thymidine assay) in a concentration dependent manner. Both 9cRA and ATRA increased insulin release, but only ATRA ralsed the GLUT 2 mRNA in a bell-shaped concentration response curve after 48,h. The insulinotropic effect of one compound is not significantly superimposed by the other indicating that the same binding sites are used by 9cRA and ATRA. The acute and chronic effects of the PPAR, agonist rosiglitazone on insulin release were additionally determined since glitazones act as transcription factors together with RXR agonists. At high concentrations (100,,m) rosiglitazone inhibited glucose (8.3,mm) stimulated insulin secretion (acute experiment over 60,min). Insulin secretion, however, was increased during a 24,h treatment at a concentration of 10,,m and again inhibited at 100,,m. Changes in preproinsulin mRNA expression were not observed. Rosiglitazone (100,,m) increased GLUT 2 mRNA paralleled by an increase of GLUT 2 protein, but only after 24,h of treatment. This data indicate that RAR and RXR mediate insulin release. The changes in GLUT 2 have no direct impact on insulin release; the inhibition seen at high concentrations of either compound is possibly the result of the observed inhibition of cell proliferation. Effects of rosiglitazone on preproinsulin mRNA and GLUT 2 (mRNA and protein) do not play a role in modulating insulin secretion. With the presence of an RXR receptor agonist the effect of rosiglitazone on insulin release becomes stimulatory. Thus the effects of RAR-, RXR agonists and rosiglitazone depend on their concentrations, the duration of their presence and are due to specific interactions. Copyright © 2001 John Wiley & Sons, Ltd. [source]


Reassessing the Cardiovascular Risks and Benefits of Thiazolidinediones

CLINICAL CARDIOLOGY, Issue 9 2008
Andrew Zinn MD
Abstract This article is designed for the general cardiologist, endocrinologist, and internist caring for patients with diabetes and coronary artery disease. Despite the burden of coronary disease in diabetics, little is known about the impact of commonly used oral hypoglycemic agents on cardiovascular outcomes. As the untoward effects of insulin resistance (IR) are increasingly recognized, there is interest in targeting this defect. Insulin resistance contributes to dyslipidemia, hypertension, inflammation, hypercoagulability, and endothelial dysfunction. The aggregate impact of this process is progression of systemic atherosclerosis and an increased risk of adverse cardiovascular outcomes. As such, much attention has been paid to the peroxisome-proliferator-activated receptor gamma (PPARg) agonists rosiglitazone and pioglitazone (thiazolidinediones [TZDs]). Many studies have demonstrated a beneficial effect on the atherosclerotic process; specifically, these agents have been shown to reduce markers of inflammation, retard progression of carotid intimal thickness, prevent restenosis after coronary stenting, and prevent cardiovascular death and myocardial infarction in 1 large trial. Such benefits come at the risk of fluid retention and heart failure (HF) exacerbation, and the net effect on plasma lipids is still poorly understood. Thus, the aggregate risk-benefit ratio is poorly defined. A recent meta-analysis has raised significant concerns regarding the overall cardiovascular safety of 1 particular PPARg agonist (rosiglitazone), prompting international debate and regulatory changes. This review scrutinizes the clinical evidence regarding the cardiovascular risks and benefits of PPARg agonists. Future studies of PPARg agonists, and other emerging drugs that treat IR and diabetes, must be designed to look at cardiovascular outcomes. Copyright © 2008 Wiley Periodicals, Inc. [source]