Dichloroacetate nanoparticles ameliorate doxorubicin’s cardiotoxicity and inflammatory effect in Ehrlich ascites carcinoma

Background: Breast cancer (BC), a prevalent malignancy significantly impacts global health. Doxorubicin (Dox), widely used chemotherapeutic agent, was effective in treating BC but is associated with dose-limiting cardiotoxicity and inflammation. This study aims to mitigate doxorubicin-induced toxicity by combining it with dichloroacetate nanoparticles (DCA-PNPs) in Ehrlich ascites carcinoma (EAC) mice model. Methods: Seventy female CD1 mice were split into ten groups (n=7). (Gp1) negative control. Groups 2 to 4 were administered intraperitoneal (i.p.) with DCA (50 mg/kg), DCA-PNPs (50 mg/kg), and Dox (0.2 mg/kg) for 2 weeks. From Gp5 to Gp10, mice were injected i.p. with EAC cells at a concentration of 0.5 × 106 cells/mouse. GP6 to GP10 were treated with Dox, DCA, DCA-PNPs, Dox/DCA, and Dox/DCA-PNPs. On day 14, biochemical parameters were evaluated. Results: The results demonstrated that the combination of Dox/DCA-PNPs exhibited reduction in cardiotoxicity and restoration of mammary gland inflammation compared to Dox alone treated group. That evidenced by improved cardiac functions tests as troponin I, T levels reduction (-91.81, -92.15 %) and decreased inflammation as CRP concentration reduced by (-69.2 %). Furthermore, decreased apoptosis of normal cardiac and mammary gland cells into (3.5 and 0.5 %), respectively. Conclusion: These findings suggest that combination of Dox/DCA-PNPs is a promising strategy for improving the therapeutic efficacy and mitigating the cardiotoxic and inflammatory side effects of Dox in BC treatment.