Cardioprotective effects of nanoemulsions loaded with natural anti-inflammatory bioactives against doxorubicin-induced cardiotoxicity in rat cardiomyocytes.

e24227 Background: Doxorubicin is a highly active antineoplastic agent; however, its clinical use is limited due to associated cardiotoxicity. This study was performed to evaluate the beneficial effects of bioavailable nanoemulsions loaded with lycopene or curcumin, both natural molecules with anti-inflammatory and vascular protective properties, against doxorubicin-induced cardiotoxicity in rat cardiomyocytes Methods: Nanoemulsions were produced by using a high-pressure homogenizer. H9C2 cells were incubated with lycopene or curcumin loaded nanoemulsions at different concentrations ranging from 0,05 up to 2% oil alone or in combination with Doxorubicin at 200 nM. Cell viability was evaluated by using a modified MTT method. The levels of lipid peroxidation products (MDA and 4-HNA), interleukins involved in cardiotoxicity (IL-6, IL-8, IL-1β), IL-10, tumour necrosis factor-alpha (TNF-α), nitric oxide (NO) were analyzed using ELISA method. Results: Nanoemulsions loaded with both bioactives showed a nanometric and homogeneous dimension in time with an overall hydrodynamic size of around 100 nm. A marked cell viability enhancement of around 35-40 % compared to only Doxorubicin-treated cells (p < 0,01) and significant reduction of lipid peroxidation (MDA and 4-HNA) in cardiomyocytes pretreated with both nanoemulsions in combination with doxorubicin. Moreover, both nanoemulsions ameliorated the cardiomyocytes release of IL-6, IL-8, IL-1β, TNF-α and NO of around 37 and 53 %, respectively and increased IL-10 production of 40-47 % compared to un-pretreated cells (p < 0,05 for all) indicating anti-inflammatory properties. Conclusions: This study demonstrates for the first time the cardioprotective effects of lycopene and curcumin loaded nanoemulsions against doxorubicin -induced cardiotoxicity. Collectively, these data indicate that pretreatment of cardiomyocytes with nanoemulsions alleviates doxorubicin-induced cardiotoxicity via reducing oxidative lipid damage, NO and cytokines release. This results places interesting initial biological evidences for subsequent cardioprotection studies in preclinical models.