Fig. 2

Histopathology of cardiac myofibrillar degeneration, contraction bands and spleen organ toxicity. Panel A (Luxol fast blue stain): The LFB stain is a specific marker of myofibrillar degeneration, and harmed cardiomyocytes are stained in different shades of blue. A1 is the section of a control animal, and the dye is not taken up by healthy cardiomyocytes. In strong contrast, doxorubicin treatment (A2-A6) caused myofibrillar degerneration as indicated by the dark blue staining and advanced irregular cytoplasmic coagulations (= contraction band necrosis as the organ specific form of an apoptotic degeneration). The light blue stained cells with their fine granular pattern (A4-A6) are initial stages of cardiomyocyte degeneration and are characterized by the splitting of myofibrils which progress to lumpy aggregates (= contraction bands, dark blue stained cells). Together, the LFB stain reveals the vast extent of myocardial degeneration. Panel B: Spleen organ weight. The spleen of rodents is of critical importance in extramedullary hematopoiesis; it therefore enables an assessment of hematoxicity and is extremely sensitive to p53 dependent cell death signaling. When compared to controls, doxorubicin caused a clear dose-related and highly significant reduction in spleen weights. Moreover, the difference in organ weight between treatments is significant. Panel C: Gross-morphology of the spleen. Depicted are the complete cross sections of controls and animals dosed at 10 mg/kg and 20 mg/kg. Note the severe dose-dependent atrophy of the spleen