Doxorubicin is a highly active antineoplastic agent, but its clinical use is limited because\nof its cardiotoxicity. Although nutraceuticals endowed with anti-inflammatory properties exert\ncardioprotective activity, their bioavailability and stability are inconsistent. In an attempt to address\nthis issue, we evaluated whether bioavailable nanoemulsions loaded with nutraceuticals (curcumin\nand fresh and dry tomato extracts rich in lycopene) protect cardiomyoblasts (H9C2 cells) from\ndoxorubicin-induced toxicity. Nanoemulsions were produced with a high-pressure homogenizer.\nH9C2 cells were incubated with nanoemulsions loaded with different nutraceuticals alone or\nin combination with doxorubicin. Cell viability was evaluated with a modified MTT method.\nThe levels of the lipid peroxidation products malondialdehyde (MDA) and 4-hydroxy-2-butanone\n(4-HNA), and of the cardiotoxic-related interleukins IL-6, IL-8, IL ... and IL-10, tumor necrosis\nfactor-alpha .... and nitric oxide were analyzed in cardiomyoblasts. The hydrodynamic\nsize of nanoemulsions was around 100 nm. Cell viability enhancement was 35â??40% higher in\ncardiomyoblasts treated with nanoemulsion + doxorubicin than in cardiomyoblasts treated with\ndoxorubicin alone. Nanoemulsions also protected against oxidative stress as witnessed by a\nreduction of MDA and 4-HNA. Notably, nanoemulsions inhibited the release of IL-6, IL-8, IL ... and nitric oxide by around 35â??40% and increased IL-10 production by 25â??27% versus cells\nnot treated with emulsions. Of the nutraceuticals evaluated, lycopene-rich nanoemulsions had\nthe best cardioprotective profile. In conclusion, nanoemulsions loaded with the nutraceuticals\ndescribed herein protect against cardiotoxicity, by reducing inflammation and lipid oxidative stress.\nThese results set the stage for studies in preclinical models.
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