Potential of Pumpkin Pulp Carotenoid Extract in the Prevention of Doxorubicin-Induced Cardiotoxicity

Background/Objectives: Doxorubicin is a chemotherapeutic agent whose clinical use is limited by side effects (SEs). The most common SE is doxorubicin-induced cardiotoxicity (DIC), for which there is still no prevention. The hypothesis arises that active substances of natural origin could influence DIC prevention by affecting several pathways of DIC occurrence. Methods: Thirty Wistar rats were divided into six groups (control, NADES (C8:C10) solvent, pumpkin pulp extract, doxorubicin, NADES (C8:C10) solvent–doxorubicin, and pumpkin pulp extract–doxorubicin). During the experiment, parameters of general condition, body, and heart weight were observed. Heart function parameters were monitored by measuring the levels of serum NT-pro-BNP, CK-MB, and hsTnT. Tissue damage was evaluated by determining the doxorubicin damage score and the expression of anti-cardiac troponin I, anti-Nrf2, anti-Bcl-2, anti-caspase-3, anti-COX2, and anti-Ki67 antibodies. Results: Doxorubicin administration led to impaired general condition of animals and increased the levels of NT-proBNP, CK-MB, hsTnT, and myocardium tissue damage of medium grade. Its administration induced apoptosis (as evidenced by elevated Casp3), reduced antiapoptotic Bcl-2 and troponin I expression in cardiomyocytes. Reduced Nrf2 expression due to doxorubicin administration was restored when pumpkin pulp extract containing carotenoids was coadministered, which led to the normalization of Casp3, Bcl-2, and troponin I expression. Consequently, the general condition and body weight were better in animals treated with both doxorubicin and the other treatment compared to those treated with doxorubicin alone. Conclusions: The results of this study strongly suggest that pumpkin pulp extract containing carotenoids has a cardioprotective effect, possibly by regulating the Nrf2 pathway.