Apremilast prevent doxorubicin-induced apoptosis and inflammation in heart through inhibition of oxidative stress mediated activation of NF-κB signaling pathways

Background: Doxorubicin is an effective, potent and commonly used anthracycline-related anticancer drug; however, cardiotoxicity compromises its therapeutic potential. Apremilast, a novel phosphodiesterase type 4-inhibitor, reported to have anti-inflammatory effects and modulating many inflammatory mediators. Methods: The present study investigated the influence of apremilast against doxorubicin-induced cardiotoxicity in male Wistar rats. A total, 24 animals were divided into four groups of six animal each. Group 1, served as control and received normal saline. Group 2 animals, received doxorubicin (20 mg kg (1), ip). Group 3 and 4, treatment group, received doxorubicin (20 mg kg (1), ip) with the same schedule as group-2, plus apremilast (10 and 20 mg kg (1) day (1), po) respectively. Oxidative stress, caspase-3 enzyme activity, gene expression and protein expression were tested. Results: The results of the present study demonstrated that administration of apremilast reversed doxorubicin-induced cardiotoxicity. Conclusion: These findings suggested that apremilast can attenuate doxorubicin-induced cardiotoxicity via inhibition of oxidative stress mediated activation of nuclear factor-kappa B signaling pathways. (c) 2018 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B. V. All rights reserved.