Nanoceria ameliorates doxorubicin induced cardiotoxicity: Possible mitigation via reduction of oxidative stress and inflammation

Doxorubicin (DOX) is one of the most commonly used anticancer drugs but its use has been limited due to constraints of cardiotoxic side effects. The precise mechanism underlying cardiotoxicity is not yet fully understood but oxidative stress has been found to be a primary mechanism behind this. In addition, DOX induced cardiotoxicity also shows involvement of proinflammatory cytokines such as IL-6 and TNF-α. Since oxidative stress plays major role in DOX induced cardiotoxicity, different antioxidants have been tried to prevent cardiotoxicity of DOX. Nanoparticles have risen up as a promising material with a wide variety of actions, and cerium oxide nanoparticles or nanoceria (NC) is one of such kind with great antioxidant potential. NC has emerged as a promising antioxidant in different pathological conditions. The present study was aimed to investigate possible protective effects of NC in DOX induced cardiotoxicity. Cardiotoxicity was induced in Swiss mice by DOX administration through i.p. route at a dose level of 15 mg/kg in two divided doses on alternate days. In our study, NC was found to mitigate cardiotoxic potential of DOX and prevented weight loss. NC restored the levels of cardiac injury markers lactate dehydrogenase (LDH) and creatinine kinase MB (CK-MB). Moreover, NC reduced malondialdehyde (MDA) levels and increased endogenous antioxidants such as reduced glutathione (GSH) and catalase levels. In addition, NC decreased proinflammatory cytokine levels and also prevented the alteration in normal structure of heart samples. Our study showed protective effects of NC in DOX induced cardiotoxicity which can become a potential therapeutic intervention against DOX induced cardiotoxicity.