Figure 18.

Cardioprotective and Chemotherapeutic Effects of Mito-TEMPOL-C₄ in the Syngeneic Rat Breast Cancer Model. (A) Effect of Mito-TEMPOL-C₄ (Mito-T (4)) alone and in combination with DOX on the tumor size. Spontaneously hypertensive rats (SHRs) were implanted with SST-2 cells and 24 h later were administered either doxorubicin (10 mg/kg), dexrazoxane (50 mg/kg), Mito-T (4) (5 or 25 mg/kg), a combination of doxorubicin and dexrazoxane, or a combination of doxorubicin and Mito-T (4). Each treatment group consisted of 10 animals. The mean tumor volumes (mm³) were measured 14 days after drug treatment. The two inset images show representative excised tumors from saline and doxorubicin-treated SHR/SST-2 animals. (B) Effect of Mito-TEMPOL-C₄ on DOXinduced cell apoptosis in cardiac tissues, as measured by monitoring caspase-3 activity. Paraffin-embedded cardiac tissues were stained with the anti-active caspase-3 antibody. The intensity of the HRP-tagged secondary antibody was quantified as an indication of active caspase-3 using the ScanScope software. Mean intensities are shown in the graph and derived from at least 10 images per animal (five animals per group). (Adapted with permission from Ref.⁴²⁰. This research was originally published in PLOS One. Dickey et al. (2013) Mito-TEMPOL and Dexrazoxane Exhibit Cardioprotective and Chemotherapeutic Effects through Specific Protein Oxidation and Autophagy in a Syngeneic Breast Tumor Preclinical Model. PLOS one 8(8):e70575. doi: 10.1371/journal.pone.0070575.)