دورية أكاديمية
Serum cardiac troponin I concentrations transiently increase in rats given rosiglitazone.
| العنوان: | Serum cardiac troponin I concentrations transiently increase in rats given rosiglitazone. |
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| المؤلفون: | Mikaelian I; Non-Clinical Safety, Hoffmann-La Roche, Inc., Nutley, NJ 07110, USA. igor.mikaelian@roche.com, Buness A, Hirkaler G, Fernandes R, Coluccio D, Geng W, Visalli T, Bachynsky MO, Berkofsky-Fessler W, Kanwal C, Hilton H, Nicklaus R, Hoflack JC, Dunn M, Sanders M, Giron M, Boyle BW, Singer T, Dick LS |
| المصدر: | Toxicology letters [Toxicol Lett] 2011 Mar 05; Vol. 201 (2), pp. 110-5. Date of Electronic Publication: 2010 Dec 21. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 7709027 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-3169 (Electronic) Linking ISSN: 03784274 NLM ISO Abbreviation: Toxicol Lett Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Amsterdam : Elsevier Original Publication: Amsterdam, Elsevier/North Holland. |
| مواضيع طبية MeSH: | Heart/*drug effects , Hypoglycemic Agents/*toxicity , PPAR gamma/*agonists , Thiazolidinediones/*toxicity , Troponin I/*blood, Animals ; Gene Expression Profiling ; Male ; Myocardium/pathology ; Organ Size/drug effects ; Rats ; Rats, Wistar ; Rosiglitazone |
| مستخلص: | Rosiglitazone, a peroxisome proliferator-activated receptor γ (PPARγ) agonist of the thiazolidinedione class, is a major insulin-sensitizing drug widely used to treat type-2 diabetes. Rosiglitazone causes myocardial hypertrophy in rodents and increases the risk of cardiac events in man. To better characterize its cardiac effects, male Wistar rats were orally administered 0, 10 or 80 mg/kg/day rosiglitazone. Myocardial gene expression profiling, hematology, histopathology and clinical chemistry, including measurement of serum cardiac troponin (cTn) I concentration with the ultrasensitive assay, were evaluated after 6 and 24h and 7 and 14 days of dosing. Heart weight was increased 10% after 7 days and 16% after 14 days of dosing at 80 mg/kg/day in the absence of microscopic changes. At the transcriptomic level, the number of differentially expressed probes was small: it was most at 24h in rats given 80 mg/kg rosiglitazone with 356 differentially regulated probes (fold change >1.3 fold, p<0.05). Also, gene categories typically associated with myocardial damage were not over-represented. Most importantly, serum cTnI concentrations in 5/9 rats after 7 days of dosing at 80 mg/kg/day were above the upper limit of serum cTnI concentration. cTnI concentrations after 14 days of dosing were similar between rats given the vehicle and rosiglitazone at 80 mg/kg. This is the first study to detect increases of serum cTnI concentrations in rats administered rosiglitazone. In light of reported cardiac events in patients chronically dosed with PPARγ agonists, our results support serum cTnI concentrations as an early biomarker of cardiac liability. (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.) |
| المشرفين على المادة: | 0 (Hypoglycemic Agents) 0 (PPAR gamma) 0 (Thiazolidinediones) 0 (Troponin I) 05V02F2KDG (Rosiglitazone) |
| تواريخ الأحداث: | Date Created: 20101222 Date Completed: 20110331 Latest Revision: 20181201 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1016/j.toxlet.2010.12.012 |
| PMID: | 21172411 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1879-3169 |
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| DOI: | 10.1016/j.toxlet.2010.12.012 |