Doxorubicin-induced cardiac toxicity is mediated by lowering of peroxisome proliferator-activated receptor δ expression in rats

The present study investigates the changes of peroxisome proliferator-activated receptors δ (pparδ) 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 pparδ and troponin phosphorylation were measured using western blot. the pparδ 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 pparδ (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 pparδ 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 pparδ in dox-induced cardiotoxicity in rats. thus,activation of pparδ may restore the expression of p-tni and the cardiac performance in dox-induced cardio toxicity in rats. © 2013 zhih-cherng chen et al.