Omega 3 fish oil-based lipid nanocapsules augment the therapeutic effects of vitamin D3 in a rat model of doxorubicin-induced cardiotoxicity

Doxorubicin is one of the most widely used and effective forms of chemotherapy. However, lethal cardiotoxicity has been associated with its clinical use. So far, no protective agent against doxorubicin-induced cardiotoxicity is available. The current study aimed to develop vitamin D3-loaded lipid nanocapsules as new appropriate protective agents against doxorubicin-induced cardiotoxicity. Physiological, anatomical, histopathological, and immunohistochemical studies were performed to assess and compare the structure and function of the heart tissue between the doxorubicin model and the other 3 groups treated with conventional vitamin D3, vitamin D3-loaded lipid nanocapsules, and vitamin D3-loaded omega-3 fish oil-based nanocapsules. Moreover, levels of LDH, CK-MB, ATP/ADP ratios, cytosolic Ca²⁺, CPN1, CaMKII-δ, oxidative and inflammatory markers, Bax: Bcl-2 ratio, and expression of P53 were measured. Results revealed that the administration of vitamin D3-loaded lipid nanocapsules effectively ameliorated signs of doxorubicin-induced cardiotoxicity, especially vitamin D3-loaded omega-3 fish oil-based nanocapsules, which nearly restored the structure and functions of the cardiomyocytes. The potential mechanism of these nanocapsules was primarily mediated by the anti-inflammatory, antioxidant, and cardioprotective effects of vitamin D3 and omega-3 fish oil. Therefore, vitamin D3-loaded omega-3 fish oil-based lipid nanocapsules could be regarded as a promising approach that paves the way for wider utilization of DOX as an efficacious antineoplastic agent with less cardiotoxic, life-threatening side effects.