Early Moderate Intensity Aerobic Exercise Intervention Prevents Doxorubicin-caused Cardiac Dysfunction through Inhibition of Cardiac Fibrosis and Inflammation

Figures

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  Figure 1. The effect of treadmill exercise on the DOX-induced AKT inhibition and up-regulation of inflammatory responses The phosphorylated AKT levels in cardiac tissues were investigated by ELISA (A). Representatives of Western blot (B), and the densitometric analysis of phosphorylated p38 (C), IκBα (D), NF-κB (E), COX-2 (F), and IL-8 (G). TNF-α levels were investigated by ELISA (H). * p < 0.05 compared to the SED group. # p < 0.05 compared to the DOX group. Detailed information about Figure 1B can be found at Figure S1.

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  Figure 2. The effect of treadmill exercise on the DOX-driven upregulation of fibrosis factors Representatives of Western blot (A) and the densitometric analysis of TGF-β1 (B), phosphorylated ERK (C), Sp1 (D), and CTGF (E). The collagen type I (F) and α -SMA (G) were tested by ELISA. * p < 0.05 compared to the SED group. # p < 0.05 compared to the DOX group. Detailed information about Figure 2A can be found at Figure S2.

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  Figure 3. The effect of treadmill exercise on the DOX-triggered upregulation of cardiac remodeling-related factors Representatives of Western blot (A) and the densitometric analysis of FGF2 (B), uPA (C), MMP-2 (D) and MMP-9 (E). * p < 0.05 compared to the SED group. # p < 0.05 compared to the DOX group. Detailed information about Figure 3A can be found at Figure S3.

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  Figure 4. Masson’s trichrome staining of the cardiac tissues. Representative image (A) and quantification (B) of the fibrosis areas. * p < 0.05 compared to the SED group. # p < 0.05 compared to the DOX group.

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  Figure 5. Examination of cardiac function using echocardiography: (A) ejection fraction; (B) fractional shortening; (C) left ventricular end-diastolic volume; (D) left ventricular end-systolic volume; (E) left ventricular internal dimension in end-diastole; and (F) left ventricular internal dimension in end-systole; (G) Representative echocardiographic M-mode images from animals. * p < 0.05 compared to the SED group. # p < 0.05 compared to the DOX group.

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  Figure 6. The effect of treadmill exercise on the concentration of two biomarkers of cardiac damage. The concentration of (A) lactate dehydrogenase (LDH) and (B) creatine kinase-MB (CK-MB) in SED, DOX, and DOX+EX groups in blood. * p < 0.05 compared to the SED group. # p < 0.05 compared to DOX group.

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  Figure 7. Schematic of the experimental paradigm After one week of acclimatization, all animals were assigned to three groups: sedentary group (SED), DOX-receiving group (DOX), and exercise during DOX treatment group (DOX+EX). All animals were subjected to echocardiography 24-h after the last intervention.