Cardioprotective effects of nanoceria in a murine model of cardiac remodeling

Abstract

Isoproterenol (ISO), a synthetic β1 adrenergic agonist is a well-known agent to be associated with severe cardiotoxicity manifested as marked myocardial necrosis and fibrosis. Oxidative stress plays a crucial role in mediating ISO induced cardiotoxicity. In present study, we have investigated the possible protective effect of nanoceria (NC) in ISO induced cardiac injury. We have given long duration exposure (a total of 10 days) of low dose ISO (20 mg/kg/day) to investigate the protective effects of NC in chronic cardiac injury model. ISO (20 mg/kg/day for 10 days) produced cardiac injury as evident by increased plasma LDH and CK-MB, AST, ALT, cardiac hypertrophy, severe myocardial fibrosis (MF) and significantly higher levels of cytokines, IL-6, TGF-β and TNF-α. Interestingly, the treatment with NC (0.2 and 2 mg/kg) abrogated cardiotoxicity symptoms and provided protection from ISO induced cardiac injury. The results from present study demonstrated strong evidences of cardioprotective effects of NC as shown by reduction in the levels of LDH (p < 0.05 at 2 mg/kg) and CK-MB (p < 0.05 at 2 mg/kg). In addition, NC reduced oxidative stress parameters MDA (p < 0.05 at 2 mg/kg) and enhanced GSH levels which is physiological antioxidant (p < 0.01 at both doses). Further, NC exhibited promising anti-inflammatory activity and curbed the levels of cytokines (p < 0.05 at 0.2 mg/kg and p < 0.001 for IL-1β and p < 0.001 at both doses for IL-6). In addition, NC also reduced the levels of pro-fibrotic cytokine, TGF-β (p < 0.05 at 2 mg/kg) and helped in reduction of collagen deposition in heart thereby, preventing the myocardial remodeling. Our results strongly suggested that NC might be of potential use as a cardioprotective agent.