Doxorubicin-Induced Cardiac Toxicity Is Mediated by Lowering of Peroxisome Proliferator-Activated Receptor δ Expression in Rats. (28th February 2013)

• Record Type: Journal Article
• Authors: Chen, Zhih-Cherng; Chen, Li-Jen; Cheng, Juei-Tang
• Other Names: Phipps Richard P. Academic Editor.
• Is Part Of: PPAR research. Volume 2013(2013)
• Publication Date: 2013-02-28
• Subjects: Peroxisomes -- Periodicals; Peroxisomal disorders -- Periodicals; 571.65505
• DOI: 10.1155/2013/456042
• Languages: English
• ISSNs: 1687-4757

Abstract

Abstract : The present study investigates the changes of peroxisome proliferator-activated receptors δ (PPAR δ ) expression and troponin phosphorylation in heart of rats which were treated with doxorubicin (DOX). Wistar rats which were treated with DOX according to a previous method. The protein levels of PPAR δ and troponin phosphorylation were measured using Western blot. The PPAR δ expression in heart was markedly reduced in DOX-treated rats showing a marked decrease in cardiac dP/dT and cardiac output. Also, cardiac troponin phosphorylation was lowered in DOX-treated rats. Meanwhile, combined treatment with the agonist of PPAR δ (GW0742) reversed the decrease of cardiac dP/dT and cardiac output in DOX-treated rats. Then, primary cultured cardiomyocytes from neonatal rats were used to measure the changes of calcium concentration in cells. In addition to both decrease of PPAR δ expression and troponin phosphorylation in neonatal cardiomyocytes by DOX, a marked decrease of calcium concentration was also observed. Our results suggest the mediation of cardiac PPAR δ in DOX-induced cardiotoxicity in rats. Thus, activation of PPAR δ may restore the expression of p-TnI and the cardiac performance in DOX-induced cardio toxicity in rats.