Comparative study on the protective effect of dexrazoxane and blueberry extract against doxorubicin-induced cardiotoxicity in rats

Fig. 1. Cardiac Topoisomerase IIβ (TOP IIβ) protein levels (ng/mg protein) across all studied groups. A significant increase was observed in the DOX group compared to the control, while combination treatment with BB and DEX markedly reduced TOP IIβ levels.

Fig. 2. Fold change in miR-140-5p gene expression in rat cardiac tissue. DOX administration significantly upregulated miR-140-5p, while treatment with BB, DEX, or their combination mitigated this elevation.

Fig. 3. Fold change in Sirtuin 2 (SIRT2) mRNA expression in cardiac tissue. DOX treatment suppressed SIRT2 expression, whereas treatment with BB, DEX, or both led to significant upregulation.

Fig. 4. Relative Nuclear factor erythroid 2–related factor 2 (Nrf2) expression levels in the heart tissue of treated rats. Nrf2 expression was downregulated in the DOX group but restored by BB and DEX treatments. Highest expression was observed in the BB + DEX + DOX group.

Fig. 5. Descriptive photomicrographs of heart section from control rat. Showing histological pattern of branched cardiac muscles, longitudinally oriented normal cardiomyocytes (↑) with eosinophilic cytoplasm and oval nuclei with granular chromatin (wavy arrows). Note connective tissue between muscle fibers (↑). (H&E- Bar 50 μm and 20 μm), (A with magnification of 400 x and B with magnification of 1000 x).

Fig. 6. Photomicrograph of rat heart section from DOX-treated group. Showing myocardial damage illustrated as distorted myocardium with impairment of cellular details, area of necrosis (elbow arrow), widened spaces (*) between the cardiac muscle fibers and inflammatory cell infiltration (short arrow). (H&E- Bar 50 μm), (magnification = 400 x).

Fig. 7. Higher magnification of the previous (Fig. 9). Showing representative area of necrosis (elbow arrow) and inflammatory cell infiltration (short arrow). (H&E- Bar 20 μm), (magnification = 1000 x).

Fig. 8. Photomicrographs of rat heart section from dexrazoxane treated group. Showing normal cardiomyocytes (↑) with eosinophilic cytoplasm and oval nuclei with granular chromatin (wavy arrows) as observed in control sections. (H&E- Bar 50 μm and 20 μm), (A with magnification of 400 x and B with magnification of 1000 x).

Fig. 9. Photomicrograph of rat heart section from group treated with BB in combination with DOX. Showing distorted cardiac muscles (↑), necrosis (elbow arrow), inflammatory cell infiltration (short arrow) and congested blood vessel (bv). (H&E- Bar 50 μm), (magnification = 400 x).

Fig. 10. Photomicrographs of rat heart section from group (VI) treated with dexrazoxane plus DOX. Showing moderate restored cardiomyocytes architecture (↑) with no cellular infiltration. Note slightly widened spaces between the cardiac muscle fibers (*). (H&E- Bar 50 μm and 20 μm), (A with magnification of 400 x and B with magnification of 1000 x).

Fig. 11. Photomicrographs of rat heart section from group (VII) treated with dexrazoxane and DOX after oral administration of BB. Showing amelioration of cardiac tissue; normal longitudinally oriented cardiomyocytes construction (↑) as seen in control group, (H&E- Bar 50 μm and 20 μm), A with magnification of 400 x and B with magnification of 1000 x).