2010
DOI: 10.1124/jpet.110.167635
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Pharmacogenomic, Physiological, and Biochemical Investigations on Safety and Efficacy Biomarkers Associated with the Peroxisome Proliferator-Activated Receptor-γ Activator Rosiglitazone in Rodents: A Translational Medicine Investigation

Abstract: Peroxisome proliferator-activated receptor (PPAR)-␥ modulators, a class of antidiabetic drugs, have been associated with cardiovascular risks in type 2 diabetes in humans. The objective of this study was to explore possible cardiovascular risk biomarkers associated with PPAR-␥ in rodents that could provide an alert for risk to humans. Normal, myocardial infarction-induced heart failure (HF) or Zucker diabetic fatty (ZDF) rats were used. Rats (n ϭ 5-6) were treated with either vehicle or rosiglitazone (RGZ; 3 o… Show more

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Cited by 16 publications
(14 citation statements)
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References 39 publications
(39 reference statements)
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“…PPAR-gamma (PPAR-γ), also known as the glitazone receptor, is the molecular target of thiazolidinediones (TZDs), and has been used for treatment of Type II diabetes mellitus (DM) in human. 225 …”
Section: Potential Strategies To Increase Klotho Proteinmentioning
confidence: 99%
“…PPAR-gamma (PPAR-γ), also known as the glitazone receptor, is the molecular target of thiazolidinediones (TZDs), and has been used for treatment of Type II diabetes mellitus (DM) in human. 225 …”
Section: Potential Strategies To Increase Klotho Proteinmentioning
confidence: 99%
“…A higher dose (6 mg/kg) was also tested, because 3 mg/kg failed to completely normalize insulin sensitivity. It is noteworthy that rosiglitazone exhibits first-order kinetics in rats, such that a doubling of the dose yields a doubling of plasma levels (Wang et al, 2010;Gao and Jusko, 2012 Surgery. After ϳ3.5 weeks on the diets, rats were weighed and anesthetized with 2% isoflurane in 100% oxygen.…”
Section: Dio Rat Modelmentioning
confidence: 99%
“…The lower dose of rosiglitazone (3 mg/kg) was chosen, because it is a frequently used efficacious dose in rats ( Törü ner et al, 2004;Khan et al, 2005;Moore et al, 2008;Wang et al, 2010). A higher dose (6 mg/kg) was also tested, because 3 mg/kg failed to completely normalize insulin sensitivity.…”
Section: Dio Rat Modelmentioning
confidence: 99%
“…Confirming these findings, by using a quantitative real-time polymerase chain reaction (rt-PCR) Wang et al . [33] evaluated gene expression profiling to assess cardiorenal safety in the heart and kidney tissue samples in adult male myocardial infarction-induced heart failure and Zucker diabetic fatty rats treated with rosiglitazone. Although variations in the expression of some genes such as ACE, PPAR -γ, IL-6 and TNF -α. were observed, authors themselves address serious doubts about the transferability of these results obtained in animal models to clinical settings [34].…”
Section: Mechanism Of Action: Role Of Ppars and Ppar-γmentioning
confidence: 99%